News

International Women’s day: THE GENDER AGENDA: GAINING MOMENTUM

The New HIV Vaccine and Microbicide Advocacy Society, in collaboration with Safehaven and her partners on the Gender Forum, jointly celebrate the International Women’s Day. We celebrate the success recorded all around the world with respect to gender responses. We also recognize the efforts made by the Nigerian government towards ensuring gender equality in all aspects of national policy formulation and programming. We continue to ask our government to be accountable to its promise and to work towards ending the various forms of violence against women and female sex workers in line with the UN theme for the 2013: A promise is a promise: Time for action to end violence against women and girls.

As the global and national HIV epidemiological data show us, the HIV epidemic continues to affect women disproportionately. This disproportionate impact affects the physical, social, economic, spiritual and psychological wellbeing of women. We therefore need to see more being done to understand and address the many factors that puts women at a disadvantage in Nigeria. We acknowledge the ongoing efforts of the National Agency for the Control of AIDS to commission operation researches one of which explores fundamentals of the gender dynamics in HIV epidemiology in Nigeria. We recognize this as a positive development. We however also recognize that there is still more to be done.

As a collective body, we call for more research and implementation science to address the impact of poor access to formal education by girls on their disproportionate risk for HIV. Evidences from our national surveys show clearly that young girls with low or no formal education are disproportionately affected by HIV. We need more concrete efforts by our national and state government to ensure young girls have access to formal education and are retained in school.

We know also that the biology of the woman increases her risk for HIV infection. Yet, there is currently little effort in the country to address the need for development of tools to enhance the ability of women to protect herself from HIV infection. We are aware of the ongoing FACTS 001 microbicide trials in South Africa. While Nigeria may not be able to host such trials, we are yet to see evidence of Nigeria being prepared to translate the outcome of those sciences into action. We therefore call on our national government and the National Agency for the Control of AIDS to start putting in place post trial access plans for microbicides and all other potential HIV prevention tools that will enhance the ability of women to protect themselves.

We also are starting to learn about the potential of DMPA – an hormonal contraceptive very popular with women in Nigeria – to increase their risk for HIV infection. The evolving evidence in the field are pointing clearing to the probability of a two-fold increased risk for HIV infection for HIV negative women who are using DMPA. We need to see our government respond to this evolving scientific evidence and find ways of ensuring women are empowered with this information so as to enable them make informed choices about contraceptive use.   

We demand that the Nigerian government be more alive to its national and global responsibility to the Nigerian woman so as to ensure an AIDS free generation which is practically impossible when the ability of women to prevent themselves from getting infected with HIV is not addressed. Collectively, we ask for prompt action by the national government led by the National Agency for the Control of AIDS to develop an action plan that will address the identified gaps enumerated above. We ask for increased investment in implementation science that will enable the country develop evidence based responses that can address the factors that increase the risk of young girls and women to HIV infection.

 

NHVMAS Statement on the VOICE Study Result

NHVMAS congratulates the team at the Microbicide Trial Network for concluding and sharing with the rest of the world and we African women a most vital piece of information that helps us to learn more about the needs of African women. We consider the outcome of the study a most useful piece of information that makes it quite clear what we women in Africa needs.

The Vaginal and Oral Interventions to Control the Epidemic study, also known as the VOICE study, released yesterday by the National Institute of Allergy and Infectious Diseases, National Institutes of Health at CROI indicates that participants provided daily oral pre-exposure prophylaxis (PrEP) did not experience any protection against HIV compared to those in the placebo arm. This is likely because very few were taking the study drugs as directed as less than one-third of participants assigned to use the product had any study drug detected in their blood. The earlier arm of the study that was looking at tenefovir gel efficacy also showed that it was not protective against HIV infection probably for the same reason. The products are however safe for use in we African women.

While the study may be interpreted as a failure to demonstrate that daily oral Truvada and oral tenofovir pill and failure of daily tenofovir gel application in the vagina to prevent HIV infection in the study participants, we at NHVMAS however do view the study as part of the piece of a jigsaw that tells us a comprehensive story about ARV based prevention.

For we at NHVMAS and the voice we represent here in Nigeria, the iPrEx study, the Partners PrEP study, the TDF2 study, the Fem-PREP and now the VOICE study are all complementary: The  iPrEx study shows clearing that  PrEP using Truvada works in men who have sex with men (MSM) and transgender women who have sex with men; the Partners PrEP study showed clearly that PrEP using Truvada and tenofovir works with serodiscordant couples including the African women who participated in the study; the TDF2 study, conducted in heterosexual men and women in Botswana, also showed PrEP using tenofovir works. Effectiveness of these products however, depends on adherence.

The VOICE study confirms what the FEM-PREP study had earlier found - for we African women, adherence to once daily pill use is a challenge and thus for us, PrEP using a once daily pill regimen will not be effective. It confirms the literally existing evidence on ground that popping a daily pill for any reason when there is no hard need for it is a challenge for many of we African women.

We African women who bear the greatest burden of the disease therefore need our partners and friends to continue with their efforts at discovering products that will enable us take the needed precaution for HIV prevention. The overall HIV incidence of 4.7% in women engaged in the VOICE study is completely unacceptable.

We in Nigeria join voices with other African women to ask for global support for the FACTS 001 study which has the potential to show that tenofovir gel used on a coitally dependent basis may make a difference to our needs.

We need all our researcher friends and partners, our donors and all critical stakeholders to invest and continue to invest in the various ring studies that has the potential for long releases of active substances that can prevent against HIV.

We also need human and financial investments in new studies that have a potential for the development of long acting PrEP wherein we women may take a single effective does of PrEP that may last for many months. Something that closely simulates what we look for in contraceptives.

We ask for continued research into the development of a rectal microbicide as the VOICE study clearly adds more evidence to the knowledge: women in Africa do engage in anal sex.

The VOICE and the FEM-PREP study is the hard evidence of the African women voices. The VOICE and FEM-PREP studies are a few of the sciences we need as we go into the future that clearly tells the world about what we women in Africa - Nigeria inclusive - need when it comes to prevention products. We need products that take cognisance of the nuances of our daily lives. We live daily with stressful challenges that may make HIV prevention not top the list of our daily priorities. It does not mean we do not care about preventing ourselves from contracting HIV infection. It simply means we need products that can fit into the reality of our daily lives.

We join the rest of the world to thank all the 5,029 sisters from South Africa, Zimbabwe, and Uganda who volunteered to participate in the VOICE trial. We also commend the Microbicide Trials Network and the National Institutes of Health for successfully implementing an incredibly important trial that has contributed more to the science of HIV prevention.

We look forward to learning more about the potential contributions of culture, norms and the entire social enterprise that the study participants live in to what the VOICE study revealed. The MTN 003c and MTN 003d are important studies for us.

 

 

Nigeria: a haven for clinical trials

Dr Ado Mohammed, a Nigerian who owns a contract research organisation with branches in Nigeria, US and UK, noted during the 1^st clinical trial summit that held in Lagos between the 15^th and 16^th of September 2012 that Nigeria is a potential clinical trial destination route. While many other presenters at the meeting discussed extensively about the challenges and obstacles there are to the conduct of good quality research in Nigeria, Dr Ado spent 40 minutes of his lecture session sharing with the over 70 participants at the conference, the large potentials there are in Nigeria for the conduct of clinical trials.

For one, the huge population of Nigeria is a great asset, he notes. Clinical researchers would rather conduct clinical trials in a single country that run trials in multiple countries. Nigeria large and diverse populations, large number of people who do not abuse drugs, large number of hospitals which can serve as points for recruitment of clinical trial participants, large number of highly skilled health care practitioners, an organised clinical regulatory system, efficient courier services, transport systems and communication networks, and registered clinical trial support services. These are all incredible assets the country should celebrate.

Dr Mohammed notes that he his not unaware of the many challenges in the country. However, these challenges are not peculiar to Nigeria. Pharmaceutical countries are ready to invest hugh resources to resolve these problems researchers can demonstrate their capacity to conduct good clinical trials that would generate world class trial results.

Prof Okoye, the President of the Association of Good Clinical Practice, one of the two organisers of the conference (the conference was organised in collaboration with NAFDAC) noted that clinical trials have the potential to generate more resources than crude oil for Nigeria. She noted that clinical research remains one of the top five national sources of income for Nigeria.

Despite the attractiveness of clinical trials, it is important to ensure and prevent the potential for abuse and exploitation. Mr Aminu Yakubu, the Desk Officer of the National Health Research Ethics Committee (NHREC), the committee in charge of health research ethics committee regulation in Nigeria, noted that the National Health Research Ethics Code is a well thought through document that can help significantly reduce research participants’ abuse. The document compliments the Good Clinical Practice document developed by NAFDAC also for clinical trial regulation. Between NAFDAC and NHREC, unethical research practices can be reduced to the barest minimum in Nigeria when all parties play their role as proscribed in the documents.

It is important to consider these potential as this meeting comes up on the heel of earlier consultative meetings held between community representative and researchers stakeholders in Nigeria in June, August and September this year. The consultative meetings were facilitated by NHVMAS in collaboration with four other partners (TIER, CADAM, IRMA, Safehaven). Community members were able to identify many research irregularities that affect the informed consent process, community engagement in research processes, and the standard of care provided for research participants. One major concern as expressed by community participants at this meeting is what often happens in many teaching hospitals: patients are made to pay for research related procedures. This is actually unethical but unfortunately, many patients are not aware of this right, noted Ms Florita Durueke, the Programme Manager of NHVMAS. NHVMAS is expending time and efforts at building capacity of members of the community to understand their rights, roles and responsibilities as research participants. We hope Nigerians will be able to learn and identify such abuses and start to speak up against these themselves, Ms Durueke commented. 

Community calls for improved ethical practices in research

COMMUNITY CALLS FOR IMPROVED ETHICAL PRACTICES IN RESEARCH

At the just concluded project organised by the New HIV Vaccine and
Microbicides Advocacy Society (NHVMAS) in collaboration with The
Initiative for Equal Rights (TIER), Christ against Drug Abuse Ministry
(CADAM), Safehaven Development Initiative and International Rectal
Microbicides Advocacy (IRMA) Nigeria, and with funding support from
Sidaction, France, participants specifically requested that the
outcome of the meeting should be widely.

The meeting conveyed members of the community resident in Lagos,Ilesa,
Osogbo, Ife, Ifon in Ogin State, Ibarapa in Ibadan, Jos and members of
vulnerable communities (FSWs,MSM, IDUs, PLHIV) to discuss about
research and how to improve research conducts within these
communities. Also, two  roundtable dialogues that facilitated
discussions between research stakeholders (researchers, bioethicists,
research sponsors, policy makers, journalists, and community members)
were conveyed in June and September 2012 in Lagos and Abuja
respectively also.

The following were the objectives of the meeting:
(i) to identify priorities considerations by research communities when
HIV research is conducted in their community
(ii) identify considerations that should be of concern to ethics
committees during protocol review
(iii) identify measures to take to empower communities to become more
directly engaged with HIV treatment and prevention research conducted
within their communities.

The community made several observations with respect to informed
consent process, community engagement in research and standard of care
in research. Please find attached the summary of the outcome of the
meetings. Some of the findings and recommendations are enumerated
below:

1.0 Informed consent and other ethical considerations in research
•      Ethics committees do not provide proper oversight function for
the researches they approve.
•      Negotiation of research reimbursements often takes place at
the time of research implementation.
•      Poor information dissemination about the research to the
research community and individuals involved with a research.

2.0. Community engagement in research
•      There is little research literacy efforts on the field.
Communities therefore only respond to what researchers share with
them.
•      CSO engagement is often mistaken for community engagement.
•      Ethics committees do not monitor researches they approve to
ensure that community engagement happens in the field.

3.0.    Concern on standard of care
•      Some research participants in hospital based research are made
to bear the cost of research related investigations.
•      Study participants may be asked to defray the cost of
managingchronic illnesses that develop during the course of
implementing
researches with long duration the onset of which researchers consider
not to study related.

4.0.    Other concerns
•      There is minimal government investment in HIV research
conducted in Nigeria.
•      A number of HIV researches are repeated due to poor
coordination of the field.
•      Often, researches do not inform intervention and policy formulation

B. RECOMMENDATION
• Informed consent form should be available in local languages for
easy understanding. Verbal translation of English to local language is
not acceptable.

• Ethics committees should monitor all the researches they approve
including monitoring of the informed consent process. The community
considers it unethical not to do so. The current level of research
monitoring is extremely low and very unacceptable. This gives room for
research participants’ abuse. Unfortunately the vulnerable - including
those that do not understand their rights when it comes to research -
are preys to multiple unethical practices including paying for
research related investigations in disguise for treatment.

• Community engagement should happen throughout the lifecycle of
research – from the design to the dissemination stage in line with the
requirements of national ethics code and national HIV research policy.

• NGOs need to be funded to actively support community research
literacy so as to promote informed community engagement with research.
Researchers are encouraged to engage CSOs in all community based
research as community educators. This would encourage mutual trust for
the research and sustained community education on the subject matter
even after the project is concluded.

• CSO engagement should not be considered as community engagement.
Researchers should work with CSO as gatekeepers only: discussion and
recruitment of research participants should be done directly from the
community after duly providing information to the community.

• All research should make effort to promote research literacy. Ethics
committees should see that the information sheet for all the research
they approve should have an educational component. This way, at the
minimum, research participants get to learn something about the
research subject.

• The  standard of care package for research participants should align
with global standards.

• Researchers should make significant efforts to facilitate mechanisms
that will increase the translation of their research findings to
policies and programmes.

Cure for HIV: A prize to keep our eyes on

 

The call for a cure was launched in February 2011 by the president-elect of the International AIDS society and Nobel Prize winner Françoise Barré-Sinoussi. The article by Lewin et al (2011) provides an excellent overview of possible promising strategies for cure using an ‘infectious disease model’ (sterilising cure model), in which HIV and all HIV-infected cells would be eliminated, or a ‘cancer model’ (functional cure model), in which there would be long-term health in the absence of treatment accompanied perhaps by low levels of HIV in the blood.

The three challenges to finding such a cure are:  (i) viral latency in resting CD4 cells (HIV lying low with its genes turned off, unaffected by antiretroviral drugs or host immune responses), (ii) residual viral
replication (with low amounts of HIV reseeding the blood stream), and (iii) reservoirs (hiding places such as the gastrointestinal tract, the brain, and the genital tract). Latently infected cells are rare (1 in 100,000 to 1 in a million) so using promising strategies such as the histone deactylase inhibitors used in cancer that could turn HIV genes on or cytokines that could activate latently infected cells to replicate so that antiretroviral therapy could take effect, may have indiscriminate effects on uninfected cells since these therapies will no select for only infected cells. The potentials for side effect will therefore be a challenge. Gene therapy with zinc finger nuclease to reduce CCR5 expression and block HIV docking is another possibility and is currently being explored in some ongoing studies.

The famous ‘Berlin’ HIV-positive patient who was treated twice for acute myeloid lymphoma with a pre-transplantation conditioning regimen, including total body irradiation, followed by transplantation of stem cells from a special donor is a point in time study of the possibility of a HIV cure (Allers et al, 2011). This patient had to undergo bone marrow transplantation twice due to leukemia. That bone marrow stem cell donor was homozygous for the CCR5Δ32 deletion (i.e. both genes coded for this deletion), meaning that his or her HIV target cells did not allow HIV to complete docking after linking with the gp120 receptor. Donor-derived memory CD4 cells replaced the recipient’s cells reaching the normal range over a 2-year period and HIV has remained undetectable in gut tissue, brain, bone marrow mononuclear cells, and peripheral blood cells (residual viral replication sites). The patient remains susceptible to HIV infection
if he is exposed to CXCR4-tropic HIV. It is impossible to analyse every cell in living humans so proving viral eradication is impossible. However, given that HIV has not reappeared after 3 years without antiretroviral therapy, the authors conclude that a cure has been achieved. With stem cell transplantation carrying a mortality of up to 30%, this procedure is not practical but this story does give hope that one day we will find a cure for HIV.

While we wait and hope for a cure in our lifetime, universal access to antiretroviral treatment remains top priority and an agenda for all nations in view of the evidence to show that treatment could also serve as a prevention tool. These are early days to be talking about a cure. But community engagement in this basic/clinical science challenge is key—this is one prize we need to keep our eye on.

(Adapted from the edits of Cate Hankins - Scientific Adviser for UNAIDS and Editor for HIV This week - Issue 91)

References:
1. Lewin SR, Evans VA, Elliott JH, Spire B, Chomont N. Finding a cure
for HIV: will it ever be achievable? J Int AIDS Soc. 2011 Jan 24;14:4.
2. Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E,
Schneider T. Evidence for the cure of HIV infection by CCR5Δ32/Δ32
stem cell transplantation. Blood. 2011 Mar 10;117(10):2791-9

 

Rethinking the risk factors for sexual risk among young persons: the evidence from analysis of South Africa and the USA

The evidence shown by the study by Pettifor AE et al throw up VERY important findings as we think about addressing the HIV risk of young people in Africa including Nigeria. As noted by Cate Hankins, the Scientific Adviser for UNAIDS, the comparison of two nationally representative surveys of young people by the authors of the study (see abstract below) starkly underscores that behaviour is not the sole determinant of HIV risk. South African young people had their first sex at a later age, have fewer sexual partners, and practise more safer sex than their American counterparts. How then can the more

than 10-fold difference in HIV prevalence be explained?

Cate's first thought goes to larger age gaps between sexual partners for the two countries. In South Africa, it is evident that women have older sex partners when compared to what is observed in the US. This means sexual mixing with older partners who can act as a bridge population to younger cohorts.... but there has to be more to it than that.

Also, in South Africa, male circumcision levels are far lower, herpes simplex 2 infection levels are higher, genital tract inflammation is higher, co-infections (tuberculosis, helminths) that can increase viral set points are more common, and the prevalence of the CCR5Δ32 coreceptor is lower.

As Cate rightly notes, social determinants such as gender power imbalances, poverty, coerced sex and rape, lack of youth friendly services, and stigma are likely playing important roles in the observed higher HIV risk observed amongst young persons in South Africa. There are however need for further studies to pull together how all these factors truly increase the risk of young persons to HIV.

The study by Pettifor et al was based on surveys conducted in 2003 (South Africa) and 2001-2 (USA) using somewhat different methodologies. Yet the findings give South Africa something to work with: they gradually are better understanding their epidemic and learning how to use their limited resources cost effectively to address their epidemic. Lets take a cue from this study and pull the multiple data we have in the country together - the many, many sentinel survey reports including the upcoming NARHS 2011 study – to learn more about the true drivers of the Nigerian epidemic. Lets pay more attention to the youths as efforts at cubbing the epidemic at this level will significantly drive down our incidence. Secondary data
analysis like the one done by Pettifor et al may well be most welcome for a country like Nigeria

Morenike Ukpong

 

The need to discuss a rectal microbicide agenda for Nigeria

I am in Ethiopia and I sat down through a 2 days session listening to data presentation about the HIV context and situation in Africa. Asusual, I was all out to hear and listen about what the data was saying

about Nigeria.

One key issue was the place and role of anal sex in driving the HIV epidemic in Nigeria. This can no longer be ignored. As per statistics, yes there are Statistics from Nigeria that shows that anal sex is
practiced by 12% of public secondary schools students (Bamidele et al, 2009). There was another presentation that showed that 12.1% of university students  and 15.2% in-school adolescents in Northern Nigeria practice anal sex.

What does this evidence mean? Anal sex is known to be the highest risk form of sexual transmission of HIV infection with approximately 14 (10 - 20) times higher risk of HIV transmission when compared to
penile-vagina sex. The probability of HIV infection transmission in penetrative anal sex is about 1.4% per sex act both in heterosexual and homosexual relationships.

There are evidence to show that about 10% of women and 14% of men in the general population practice anal sex with condom use being low during this sexual practice as a result of multiple erroneous believes including believes that anal sex is safer than vagina sex. Request for anal sex by clients of FSW is high (not a negligible proportion) with men paying higher to have anal sex with sex workers (male and female) for many reasons (more pleasurable, tighter, gets to ejaculate faster and for prevention of STIs, and it is cleaner as fewer people engage with this 'hole').

And you know what? For women, the risk is highest as they will always be the receptor in either vagina or anal sex. Maybe this be an unidentified driver of the HIV epidemic amongst females. Study do show
that many women engage in anal sex during pregnancy, menstruation, for pleasure and a whole host of other reasons. Yet evidence show that as receptors of sex (anal or vagina) their risk are increased.

What do we need to do? I personally think there is the need to discuss more openly about the risk of anal sex. Many times we discuss sex during our sex, sexuality and HIV education in a way that
unconsciously limit our verbal and non verbal communication about sex to vagina sex. Our discussion around sex must become broader to encourage public understanding of the multiple forms of sexual
practices (vagina, oral, anal) and the risk of HIV infection associated with all the forms of sex. I had personally been engaged in a public discuss with university students where a major player in the
HIV field actually noted in her discuss that anal sex was safe. Anal sex is associated with high risk and we need to get the public to understand this. Our family life education series need to identify
this and share this information in schools in view of the statistics that show that despite under-reporting, 12% -15% of adolescents practice anal sex.

Do we discourage anal sex? People have choices. We need to promote safe practices. Anal sex and howbeit all sexual practices need to be made safe (use dental dams for oral sex, condom for vagina sex, and condom + lubricants for anal sex and vagina sex with the vagina is dry). These are existing tools and are effective. We need to advocate for increased distribution and access to lubricants in the same spaces as condoms can be accessed. And for the future, there is the rectal microbicide.

What is rectal microbicide? It is a product currently being developed. When developed, it will be available as a lubricant, gel, douche or an enema that can be used by women and men to reduce the risk of HIV transmission during anal sex. It would be able to offer some level of protection from HIV infection even in the absence of a condom. It would also serve as a backup protection if a condom breaks or slips
off during anal intercourse. For more information, visit www.rectalmicrobicides.org

Some Nigerian researchers are very much interested in conducting rectal microbicide research. Lets support this process. Lets speak up for rectal microbicide in Nigeria. Lets discuss about this during our
World AIDS day activities as we ensure a AIDS free generation.

Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study

Renee Heffron, Deborah Donnell, Prof Helen Rees, Connie Celum, Nelly Mugo, Edwin Were, Guy de Bruyn, Edith Nakku-Joloba, Kenneth Ngure, James Kiarie, Robert W Coombs, Jared M Baeten

Lancet Infect Dis. 2012 Jan;12(1):19-26. Epub 2011 Oct 3. 

Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. Heffron and colleagues aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. In this prospective study, they followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, they compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. Cox proportional hazards regression and marginal structural modelling were used to assess the effect of contraceptive use on HIV-1 risk. Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6–24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06–3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8–24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12–3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, andabout the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1.

For abstract access click here: http://www.ncbi.nlm.nih.gov/pubmed/21975269

Use of injectible hormonal contraceptives and risk of HIV-1 transmission

There have been suggestions about the increased HIV infection risk with the use of  hormonal contraception. Prior to this study, observational studies have suggested a possible link with observed increased risk of HIV infection with the use of hormonal contraceptives. This study of HIV serodiscordant couples , while not specifically designed to examine this issue, further provides evidence to the possible link between the use of ijectable contraceptive and increased HIV risk. The study showed a doubling of the risk of HIV acquisition for HIV-negative women using injectable DMPA (depot-medroxyprogesterone acetate) and a doubling of the risk of HIV transmission from HIV-positive women using DMPA to their seronegative partners. 

Cate Hankins, the Scientific Adviser for UNAIDS notes that 'while contraception improves the health of women and children worldwide, and plays a crucial role in helping women with, or at risk of, HIV infection to prevent the adverse social and health consequences of unintended pregnancies, it is important to examine the meaning and implication of these evolving evidences. In view of this, WHO and partners are convening a technical consultation in early 2012 to re-examine the totality of evidence on the potential effects of hormonal contraception and of intrauterine devices on HIV acquisition, disease progression, and infectivity/transmission to sexual partners. The need to conduct randomized controlled trials to determine whether hormonal contraception increases the risk of HIV acquisition in women and/or of HIV transmission to men will be assessed.  In the meantime, we need to reinforce the importance of correct and consistent condom use, regardless of whether another method of contraception is being used. It is and has been for decades the ‘dual protection’ message'.

While we wait for the outcome of the WHO consultative meeting, it is important for those in the field to be aware of the evolving evidence and its potential implications in the design of HIV prevention services for serodiscordant couples at the least. Below is the abstract of the study. 

Implication for HIV prevention research protocol development and review: It may be important that when researchers plan HIV prevention studies, it will be important to factor the role that injectible hormonal contraceptives can plan in HIV acquisition during the data analysis process.

End of project report: Building capacity of laypersons to communicate NPT trial results

The importance of building the capacity of  the community, including the media, in  understanding and communicating  biomedical HIV trial

results is well recognised. Not only will it ensure  effective media communication, it will also promote community engagement in media
discourse.

The project “Building Community Engagement in Vaccines Efforts in Canada and Africaâ€, is a North-South Collaboration involving NHVMAS, Southern African AIDS Trust, South Africa, and ICAD, Canada. The aim of the 3 years project was to assist community representatives and the media to understand and communicate HIV trial results.

The objectives of the project include among others to develop a toolkit and training package on New Prevention Technologies research and to deliver  training workshops to the community representatives and media/journalists in Canada, Nigeria and Southern Africa. NHVMAS administered the Nigerian regional component of this collaboration from January 2010 to September, 2011.

For this project, NHVMAS worked in partnership with CSOs, most at risk populations (MARPs) the print and electronic media in four
geopolitical zones in Nigeria namely Lagos, Abuja, Enugu and Kaduna.  A focused training for media/journalists was conducted in Sagamu. At the end of the project, 64 members of CSO, 23 journalists, 18 health workers, one researcher, one policy maker and four students were trained over the 18 months

period of the project. Information, Education and communication materials comprising of 3 sets of posters on NPT were developed and produced.

Based on pretest, post test and post training evaluations, it was very clear the the project was able to increase the knowledge  and understanding of trainees on NPTs. There was increased media reporting/publications on NPT (reports aired on Lagos State radio and television, and published on print media-Vanguard, Tribune, Daily independent and the Nation). All the trainees met during the evaluation exercise had also integrated knowledge and skills gained during the training into their organisations' community education and outreach activities. Other outcomes include the use of the training tool to design research literacy training for 16 peer leaders who work with FSWs, IDUs, MSMs and PLHIV.

As a next step, NHVMAS shall look for mechanisms to replicate the trainings in many more communities of CSOs, and for journalists. As a first step in this direction, the team (SAT, ICAD and NHVMAS) shall organise and abrigded version of the training at ICASA on the 4th of December 2011 between 1.00pm and 4.00pm at Harmony Hotel, Ethiopia. More details about the training will be sent out. For all those planning to be at ICASA, please put this on your calender and share the information with others.

A simpler tool for estimation of HIV incidence from cross-sectional, age-specific prevalence data

A simpler tool for estimation of HIV incidence from cross-sectional,
age-specific prevalence data

REFERENCES: Journal of Epidemiology and Community Health. 16 June 2010
AUTHORS: Rajan SS and Sokal
Dhttp://jech.bmj.com/content/early/2010/06/16/jech.2009.091959.short?q=w_jech_ahead_tab
Background HIV incidence estimates are crucial in understanding and predicting the HIV/AIDS epidemic and identifying sub-populations and regions most at risk for the epidemic. However, incidence estimation is a challenge due to the nature of the disease and type of data available. This paper aims to present a simple and creative HIV incidence estimation method for resource constrained settings with scarce data.

Methods The authors developed a simple user-friendly non-iterative spreadsheet estimation method, which can produce incidence estimates by age group using observed cross-sectional, age-specific HIV prevalence. Data from two prospective FHI microbicide Phase III clinical trials in Nigeria were used to validate the spreadsheet method. Since both the clinical trials involved condom use promotion to reduce HIV risk, the authors also used the AVERT software to estimate the extent of incidence reduction due to the intervention.
Results The spreadsheet incidence estimates after accounting for AVERT adjusted reductions, for age groups 18-20, 21-25 and 26-30 were: 1.69%, 0.96% and 1.12% in the SAVVY trial, and 2.11%, 1.47% and 1.28% in the CS trial respectively. The corresponding actual observed incidence rates were 1.62%, 2.39%, and 1.13% in the SAVVY trial and 1.93%, 1.78% and 1.40% in the CS trial.

Conclusion Comparisons of the spreadsheet-estimated incidence with the actual incidence from the clinical trials demonstrated that the method is reasonably accurate in its estimation. Because of the method's limitations it should not be used to evaluate HIV/AIDS prevention interventions or without understanding the direction of the bias in
the case of an evolving HIV epidemic. 

Age related HIV incidence among sex workers

 

Age related HIV incidence among sex workers

The result of the study below shows that the HIV incidence (rate of new HIV infection) among sex workers (the community with the highest HIV prevalence in Nigeria) is still low compared to countries like South Africa (with a HIV incidence as high as 5.0%). However, when you read the data shown in the abstract below, it is clear that the HIV incidence is highest in the age group 18 to 20 years in both the SAVVY and the CS3 trial. Is this a possible pointer to our target group among FSW in Nigeria?

Full paper can be accessed at
http://jech.bmj.com/content/early/2010/06/16/jech.2009.091959.short?q=w_jech_ahead_tab

 

HIV incidence data for FSW in Nassarawa - Report from Biotech Initative, Nigeria

 

HIV incidence data for FSW in Nassarawa - Report from Biotech Initative, Nigeria

We estimated the HIV incidence among commercial female sex workers (FSWs) in north central Nigeria using bimodal methodology. Using a cross-sectional study design, a total of 900 active FSWs between the ages of 18 and 35 years were recruited from 52 brothels within Nasarawa State, Nigeria. 

A rapid test algorithm was used to determine their HIV status. The BED IgG–Capture enzyme immunoassay (CEIA) was applied on the HIV-seropositive samples to detect recent HIV-1 infection for the estimation of incidence among those with HIV infection. 

Of the 900 FSWs tested, 335 (37.2%) were found to be positive for HIV. Of these, 63 showed evidence of recent infection. Using two third-generation BED analysis approaches that account for false-recent rate, an annualized adjusted HIV incidence of 11.97% (95% CI:8.51–15.43%) and 12.36% (95% CI: 8.18–16.34%) was observed; difference P > 0.05. In addition, 875 (97.2%) of the FSWs readily agreed to participate in HIV clinical trials. 

The report of this study shows that there is a feasibility for conducting HIV prevention trials in Nigeria among FSW with a high incidence of HIV. The infrastructural and human capacity also exists. Also, the high proportion of recent HIV infections among FSWs in Nigeria also provided an enabling environment for future studies of HIV prevention.

 

Original article

Estimates of human immunodeficiency virus incidence among female sex workers in north central Nigeria: implications for HIV clinical trials

Joseph C. Forbia, Peter E. Entonua, Lulu O. Mwangib, Simon M. Agwale

2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd.

 

Treating HIV-infected People with Antiretrovirals Protects HIV-negative Partners from Infection

 

 

Treating HIV-infected People with Antiretrovirals Protects HIV-negative Partners from Infection

The study was designed to evaluate whether immediate versus delayed use of ART by HIV-infected individuals would reduce transmission of HIV to their HIV-uninfected partners and potentially benefit the HIV-infected individual as well.  Findings from the study were reviewed by an independent Data and Safety Monitoring Board (DSMB).  The DSMB recommended that the results be released as soon as possible and that the findings be shared with study participants and investigators. The DSMB concluded that initiation of ART by HIV-infected individuals substantially protected their HIV-uninfected sexual partners from acquiring HIV infection, with a 96 percent reduction in risk of HIV transmission. HPTN 052 is the first randomized clinical trial to show that treating an HIV-infected individual with ART can reduce the risk of sexual transmission of HIV to an uninfected partner.

NHVMAS wants to thank the team for a wonderfully implemented study that has given us evidence about not just the possible role of HIV treatment in HIV prevention, but also the potential impact of early HIV treatment in reducing morbidity and mortality.

Read more details about the study below 

Men and women infected with HIV reduced the risk of transmitting the virus to their sexual partners by taking oral antiretroviral medicines when their immune systems were relatively healthy, according to findings from a large-scale clinical study sponsored by the National Institute of Allergy and Infectious  Diseases (NIAID), part of the National Institutes of Health. 

The clinical trial, known as HPTN 052, was slated to end in 2015 but the findings are being released early as the result of a scheduled interim review of the study data by an independent data and safety monitoring board (DSMB). The DSMB concluded that it was clear that use of antiretrovirals by HIV-infected individuals with relatively healthier immune systems substantially reduced transmission to their partners. The results are the first from a major randomized clinical trial to indicate that treating an HIV-infected individual can reduce the risk of sexual transmission of HIV to an uninfected partner. 

“Previous data about the potential value of antiretrovirals in making HIV-infected individuals less infectious to their sexual partners came largely from observational and epidemiological studies,” said NIAID Director Anthony S. Fauci, M.D. “This new finding convincingly demonstrates that treating the infected individual—and doing so sooner rather than later—can have a major impact on reducing HIV transmission.”

 

Led by study chair Myron Cohen, M.D., director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill, HPTN 052 began in April 2005 and enrolled 1,763 couples, all at least 18 years of age. The vast majority of the couples (97 percent) were heterosexual, which precludes any definitive conclusions about effectiveness in men who have sex with men. The study was conducted at 13 sites in Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, the United States and Zimbabwe. The U.S. site collected only limited data because of difficulties enrolling participants into the study. However, data from one serodiscordant couple at the site was included in the DSMB’s analysis. At the time of enrollment, the HIV-infected partners (890 men, 873 women) had CD4+ T-cell levels—a key measure of immune system health—between 350 and 550 cells per cubic millimeter (mm³) within 60 days of entering the study. The HIV-uninfected partners had tested negative for the virus within 14 days of entering the study.

 

The investigators randomly assigned the couples to either one of two study groups. In the first group, the HIV-infected partner immediately began taking a combination of three antiretroviral drugs. In the second group (the deferred group), the HIV-infected partners began antiretroviral therapy when their CD4 counts fell below 250 cells/mm³ or an AIDS-related event, such as Pneumocystis pneumonia, occurred. Throughout the study, both groups received HIV-related care that included counseling on safe sex practices, free condoms, treatment for sexually transmitted infections, regular HIV testing, and frequent evaluation and treatment for any complications related to HIV infection. Each group received the same amount of care and counseling.

 

In its review, the DSMB found a total of 39 cases of HIV infection among the previously uninfected partners. Of those, 28 were linked through genetic analysis to the HIV-infected partner as the source of infection. Seven infections were not linked to the HIV-infected partner, and four infections are still undergoing analysis. Of the 28 linked infections, 27 infections occurred among the 877 couples in which the HIV-infected partner did not begin antiretroviral therapy immediately. Only one case of HIV infection occurred among those couples where the HIV-infected partner began immediate antiretroviral therapy. 

 

This finding was statistically significant and means that earlier initiation of antiretrovirals led to a 96 percent reduction in HIV transmission to the HIV-uninfected partner. The infections were confirmed by genetic analysis of viruses from both partners. 

Additionally, 17 cases of extrapulmonary tuberculosis occurred in the HIV-infected partners in the deferred treatment arm compared with three cases in the immediate treatment arm, a statistically significant difference. There were also 23 deaths during the study. Ten occurred in the immediate treatment group and 13 in the deferred treatment group, a difference that did not reach statistical significance.

 The study was designed to evaluate whether antiretroviral use by the HIV-infected individual reduced HIV transmission to the uninfected partner and potentially benefited the HIV-infected individual as well. Additionally, the study was designed to evaluate the optimal time for a person infected with HIV to initiate antiretrovirals in order to reduce HIV-related sickness and death. Based on their analysis, the DSMB recommended that the deferred study arm be discontinued and that the study participants be informed of the trial’s outcome.

 “We want to thank the study participants for making such an important contribution in the fight against HIV/AIDS. We think that these results will be important to help improve both HIV treatment and prevention,” said Dr. Cohen.

Study participants are being informed of the results. Individuals who became HIV-infected during the course of the study were referred to local services for appropriate medical care and treatment. HIV-infected participants in the deferred treatment group will be offered antiretroviral therapy.  The study investigators will continue following the study participants for at least one year.

The study was conducted by the HIV Prevention Trials Network, which is largely funded by NIAID with additional funding from the National Institute on Drug Abuse and the National Institute of Mental Health, both part of the NIH. Additional support was provided by the NIAID-funded AIDS Clinical Trials Group. The antiretroviral drugs used in the study were made available by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/Viiv Healthcare and Merck & Co., Inc.

The 11 HIV drugs that were used in various combinations included the following:

• atazanavir (300 mg once daily)

• didanosine (400 mg once daily)

• efavirenz (600 mg once daily)

• emtricitabine/tenofovir disoproxil fumarate (200 mg emtricitabine/300 mg tenofovir disoproxil fumarate once daily)

• lamivudine (300 mg once daily)

• lopinavir/ritonavir 800/200 mg once daily (QD) or lopinavir/ritonavir 400/100 mg twice daily (BID)

• nevirapine (200 mg taken once daily for 14 days followed by 200 mg taken twice daily)

• ritonavir (100 mg once daily, used only to boost atazanavir)

• stavudine (weight-dependent dosage)

• tenofovir disoproxil fumarate (300 mg once daily)

• zidovudine/lamivudine (150 mg lamivudine/300 mg zidovudine taken orally twice daily)

For additional information about the HPTN 052 study, see the Questions and Answers. Visit the NIAID HIV/AIDS Web portal for more information about NIAID’s HIV/AIDS research.

 

 

Adaptive Clinical Trials Design - Part II

Adaptive Clinical Trials Design - Part II

Moderator's Note: Please if you have questions or clarification to be made about Adaptive clinical Trial design, please do note we have the author of this piece online who will be ready to give further details and answer all questions. The part I of this posting was posted earlier. We hope to send in a three more postings to help us all understand this evolving concept for HIV prevention research. Happy reading.                                                               

In the clinical trials realm, Adaptive Clinical Trial Design (ACTD) is a clinical trial methodology that is rapidly gaining popularity and acceptance.  The primary reason for this phenomenon is due to the increasing cost of operating clinical trials which is often the by-product/causality of high failure rates of clinical trials.  ACTD has many advantages to facilitate the effectiveness of clinical trial operations.  However, as a relatively new methodology, it does have its challenges as well.  

In this segment of our three-part article on Adaptive Clinical Trial Designs, we will (1) provide an overview on what ACTD is, (2) describe how it differs from the standard clinical trials designs, and (3) briefly highlight some of the advantages and disadvantages of ACTD.   In subsequent articles, we will (1) describe in greater details the pros/cons of ACTD, (2) describe regulatory authorities perspective and guidance on the topic and (3) offer recommendations on how to implement ACTD.

So, what exactly is Adaptive Clinical Trial Designs?  In accordance to the 2010 FDA Guidance for the industry on “Adaptive Design Clinical Trials for Drugs and Biologics,â€� an adaptive design clinical study is defined as:

 A study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data (usually interim data) from subjects in the study.  Analyses of the accumulating study data are performed at prospectively planned time points within the study, can be performed in a fully blinded manner or in an un-blinded manner, and can occur with or without formal statistical hypothesis testing.

It has been argued by some that researchers do routinely modify clinical studies during the course of the studies via aProtocol Amendment� or Protocol Modification.� Modification in clinical trials may include administrative changes, early trial termination, addition/removal of treatment arms, changes in trial sample population size, and treatment arm allocation regimen.  How so, does this then differentiate ACTD from standard or conventional clinical trial designs?  

There are two operative terms in the above definition for adaptive studies:  prospectively and modification.   Conventional clinical trial designs often use fixed or pre-determined sample sizes that do not use adaptive elements.  In other words, with ACTD, anticipated changes are planned before the study commences and adjusted accordingly.  On the other hand, with conventional studies, changes/amendments are allowed to be made after the commencement of a study for safety or administrative reasons if they do not impact the integrity of the data collected or statistically alter the initial statistical design or hypothesis of the study.

As described in the aforementioned FDA Guidance on Adaptive Design Clinical Trials, the three main advantages for adaptive clinical trials are that it:

•         Allow studies to be operated more efficiently and provides the same information

•         Increases the likelihood of success on the study objective

•         Yields improved understanding of the treatment’s effect (e.g., better estimates of the dose-response relationship or subgroup effects, which may also lead to more efficient subsequent studies). 

The advantages, however, need to be cautiously weighed with the increase likelihood of introducing study bias with a poorly designed or poorly implemented adaptive methodology.  This is a major disadvantage and concern that is shared by regulatory authorities such as the FDA, drug developers, and the end users (i.e., customers).  

As previously mentioned, this is simply a brief introduction to adaptive clinical trials methodology.  Additional details will be provided in subsequently articles.  However, for those eager to immediately learn more about Adaptive Clinical Trials Designs, below are three recommended readings:

1. Guidance for Industry . Adaptive Design Clinical Trials for Drugs & Biologics.  US Department of Health and Human Services; Food and Drug Administration.  February 2010.

2. The Agile Approach to Adaptive Research.  Written by Michael Rosenberg.  Published by John Wiley & Sons, February 2010.

3. Adaptive Clinical Trials: The Promise and the Caution.  Written by Donald Berry.  Published in Journal of Clinical Oncology, December 2010.

Adaptive Trial Design 1: An Overview

Adaptive Trial Design 1: An Overview

Adaptive trial design refers to a clinical trial methodology that allows trial design modifications to be made after patients have been enrolled in a study, without compromising the scientific method. In order to maintain the integrity of the trial, these modifications should be clearly defined in the protocol. 

 When designed well, an adaptive trial empowers sponsors to respond to data collected during the trial. This is achieved by re-focusing the trial in a way that maximises the impact of each subject’s contribution. Examples of adaptive trial designs include dropping a treatment arm, modifying the sample size, balancing treatment assignments using adaptive randomisation or simply stopping a study early for success or failure.

 In a standard trial, safety and efficacy data are collected and reviewed by a monitoring board during scheduled interim analyses. However, aside from stopping a study for safety reasons, very little can be done in response to that data. Often, a whole new study must be designed to further investigate key trial findings.

 In an adaptive trial, the sponsor might have the option of responding to interim safety and efficacy data in a number of different ways, including narrowing the trial focus or increasing the patient population. An example of narrowing the trial focus includes removal of one or more of the treatment arms based on predetermined futility rules. Alternatively, if the data available at the time of the review do not allow for a clear decision between utility and futility, it might be decided to expand the enrolment of patients on one or more treatment arms beyond the initially targeted sample size.

 Another example of adaptive design is the response-adaptive. In a response-adaptive setting, patients are randomised to treatment arms based on the response to treatment of previous patients. In a response adaptive trial, real-time safety and efficacy data can be incorporated into the randomisation strategy in order to influence subsequent adaptive randomisation decisions on a patient-by-patient basis. An example of response-adaptive randomisation is “play-the-winner”, which assigns patients to treatment arms that have resulted in fewer adverse events or better efficacy.

 As these examples demonstrate, the adaptive design concept can be utilised in a number of different ways to increase trial flexibility. In a well-designed adaptive trial, that flexibility can result in lower drug development costs, reduced time to market and improved patient safety. Cost reduction is achieved by stopping unsuccessful trials earlier, identifying successful trials sooner, dropping unnecessary treatment arms or determining effective dose regimens faster. 

 Time to market can be accelerated by identifying successful trials sooner and reducing, or removing entirely, the lead time between trial phases, especially Phases II and III. Patient safety is improved because adaptive trials tend to reduce exposure to unsuccessful treatment arms (which are dropped early), and increase access to effective treatment arms (via response adaptive randomisation).

 Article written by: Eva Miller, Manager of Biostatistical Services, Stephane Deleger, West Coast Business Development Manager, and Jim Murphy, Vice President of Business Development and Marketing at Interactive Clinical Technologies, Inc (ICTI)

 The authors can be contacted at info@icti-almac.com

 Full paper can be accessed at: http://www.pharmaceutical-int.com/article/implementing-and-managing-adaptive-designs-for-clinical-trials.html

Perceptive survey highlights growing interest in adaptive trial designs

Perceptive survey highlights growing interest in adaptive trial designs

DATE: 26 April 2011

SOURCE: Outsourcing-Pharma.com

AUTHOR: Alexandria Pesic

http://www.outsourcing-pharma.com/Clinical-Development/Perceptive-survey-highlights-growing-interest-in-adaptive-tria... 

Perceptive Informatics, the eClinical Solutions provider and Parexel subsidiary, has released the results of a global survey which shows a growing interest in the implementation of adaptive trial designs. Entitled "Implementing Bayesian Response Adaptive Trials," the survey was conducted during a recent webinar presented by Perceptive and UK-based science and technology consultants, Tessella. It canvassed the opinion of more than 300 industry professionals representing a broad range of clinical, statistical and regulatory functions. The results revealed that 80 per cent of respondents were considering implementing some type of adaptive design in the next twelve months. Of that 80 per cent, 76 per cent were considering designs that drop treatment arms at fixed interim analyses. However, only 24 per cent of respondents said they expected to implement designs that regularly adjust the randomisation ratio throughout the study - a technique known as response adaptive design.

Commenting on the findings, Damian McEntergart, senior director of statistics and product support at Perceptive, said: "Following the FDA draft guidance on adaptive trials, increasing implementation of these designs has helped to alleviate regulatory acceptance concerns within the industry." An important requirement for adaptive trials is the ability to include more dose levels in Phase II dose-finding studies without significantly increasing the number of study participants or the length of timelines."

Workshop on Interpreting and communicating biomedical HIV prevention research trial results

 

The New HIV Vaccine and Microbicide Advocacy Society, Lagos announces a workshop on Interpreting and communicating biomedical HIV prevention research trial results

 

Date : February 22nd to 24th, 2011
Venue: Abuja, Nigeria

Rationale:
There are increasing numbers of biomedical HIV prevention research being planned, and ongoing. The outcome of these global research efforts have implications the national HIV prevention programming in Nigeria and the various HIV prevention work we conduct in the community. Nigeria will also be engaged in various biomedical HIV prevention research efforts in the near future. This training will address the capacity needs of those who work at the grassroot on how to interprete the various biomedical HIV prevention research trial results and how the results can be effectlively communicated to members of their community in a timely and useable fashion.

Workshop Objectives:
At the end of the workshop, participants will be able to:
- Understand the rationale for biomedical HIV prevention research

- How biomedical HIV prevention researches are designed

- Ethical considerations in the design and impementation of biomedical HIV prevention research

- Statistical considerations in biomedical HIV prevention research

- How to interprete the published results of clinical trials

- How to communicated and use the results of these trials in the community

Workshop Contents:

- Basic definitions of New HIV prevention technologies (NPT)

- The need for NPT researches

- Overview of NPT researches

- Actors in the field of NPT research

- State of NPT research

- Ethics of NPT research

- Analysis of NPT clinical trial results

- Communicating results and use for designing programmes

- Next steps

The workshop is designed to be participatory with the use of multiple tools to facilitate understanding of research concepts and statistics. Hands-on experience in designing plans for community education on biomedical HIV prevention trials will be gained by doing exercises, and working in small groups throughout the workshop. The participant groups will present the results of their exercises and group discussions during the workshop.

Eligibility:
The course is designed for Members of CSOs, community liasions, and field workers affiliated to reseach sites. Interested journalists, ethics committee members are also welcome.

 

Faculty:
This workshop will be taught by experts from the New HIV Vaccine and Microbicide Advocacy Society using tools that have been pretested.

 

Application procedures & Submission:

Space limited to only 30 applicants.

For further information, comments and reservation please contact Aisha Abdullahi <aishatuabdullahi@yahoo.com>; Florita Durueke <chi chiflorita@yahoo.com>; Augusta Obyamiziam obyamuziam@yahoo.com

 

One antiretroviral pill a day may keep HIV infection away: call for action NHVMAS outlines potential next steps for the Nigerian Community

The result of the iPrEx study anounced on the 23rd of November 2010 brings lots of new excitement and hope to the field of HIV prevention. The study showed that the use of one antiretroviral pill– Truvada – consistently  every day has the potential of
reducing the risk of contracting HIV infection by up to 92-95%.
The study was conducted amongst 2,499 MSM study participants recruited in Brazil, Ecuador, Peru, South Africa, Thailand and USA. The study involved having some of these participants take Truvada every day while other participants took a pill that
looks like Truvada but was not active like Truvada (a placebo). All study participants visted the clinic every month and got tested to check for HIV infection, proper kidney function, and possibility of HIV drug resistance. Study participants were also asked to report on their daily drug use. The pills not used were counted at every study visit. The pills taken by each study participants was calculated by substracting the number of pills left from the number of pills dispensed. Also, in a few participants, blood was taken to examine if there was traces of the drug in their blood as evidence of taking the drug. Analysis of the result showed that:
(i) based on the self report, Truvada is 43.8% effective in prevention new HIV infection among MSMs who engage in sex

(ii) the drug was more protective in study participants who took the drug regularly.For those who took the drug at least 50% of the time based on pill counting, the drug was able to reduce the risk of HIV infection during sex by 50.2%. For those who used the drug at least 90% of the time, the drug was able to reduce the risk of HIV infection during sex by 72.8%.

(iii) having detectable levels of Truvada in the blood was associated with reduced chances of contracting HIV infection when on daily drug regimen. It does not completely eliminate the chances though

(iii) if drug adherence were to be 100%, the drug can possible confera 92-95% protection from HIV infection.

(iv) The drug was found safe with mild side effect. No HIV negative study participant who the trial developed HIV resistance. Neither did any of the study participants who seroconverted. The two study participants who developed resistance appear to have been infected with HIV before their study enrollment.

What does this mean to us as Nigerians?
1. Call to the National Agency for Food and Drug Administration and Control (NAFDAC): Access to ARVs remains extremely difficult in some communities in Nigeria. Currently, access is easier only in the big towns and cities and clustered only in locations that are far difficult to reach for many people living with HIV who need the ARVs.  Implementation of PrEP may therefore face its challenges in Nigeria. Unfortunately, wide spread understanding of the potential high benefits of PreP may create a demand for the drug that cannot be met through hospital based services. The thriving black drug market in Nigeria may once again have a potential veritable market for the Truvada as a PreP. NHVMAS calls on NAFDAC to play its critcal role at this time: it need to understand the potential for fake drug sales, and position itself to play a critical important role in preventing fake ARVs sales, especially Truvada, in the market cannot be overemphasised.

2. Call to all International Partners and stakeholders working with MSMs in Nigeria:  Even in places where access to ARVs is more stable, PrEP will likely be targeted to groups most at risk for HIV, including MSMs. This would in turn require disclosure of same-sex behaviour, which could prove difficult or even dangerous in a country like Nigeria where violence, stigma and discrimination, and legal restrictions against MSM persists.  In a country where MSMs have an HIV incidence that is five times the national average, where MSMS are well know to serve as a bridge for HIV infection to the general population, addressing potential barriers to PreP access needs to be expediated now. NHVMAS calls on all stakeholders working with MSMs should address potential barriers to MSMs’ access to PreP when programmes start to roll out.  

3. Call to The National Agency for the Control of HIV/AIDs (NACA) and HIV prevention implementing partners: Truvada is not a magic bullet. Trial participants also had access to suitable HIV prevention tools such as STI management, consistent and regular education on HIV prevention include correct and consistent use of condoms and lubricants, condoms,  and monthly HIV testing in addition to the pills. This may have been an important contributing factor underlying these encouraging results. Unfortunately, these additional existing HIV prevention tools ave still out of reach of the general population and less so MSMs. An estimated 90 percent of MSM globally lack access to even the most basic prevention services.  To achieve true combination prevention, we must not only significantly expand access to ARVs, but also promote much greater access to condoms, lubricant and other basic sexual health services for all those who need it irrespective of gender, sexual orientation and wealth. NHVMAS therefore calls on NACA, all HIV prevention implementing partners and programmers to intensify efforts at facilitating community access to existing HIV prevention tools even as plans are been made for the roll out of PreP.

4. Call to advocates: One challenge the trial highlighted is that adherence to drug use. Evidence show that the effectiveness of the drug increased with improved adherence. The trial reported that only about half of study participants took the medication consistently.  NHVMAS calls on all advocates and HIV community educators to include information on HIV prevention technologies in their HIV prevention messages so as to start discussion the issue of adherence, combination prevention, and the implication of partial efficacy of PreP and other biomedical HIV prevention tools being developed now prior to drug roll out.

5. Call to People Living with HIV: With more and more research evidence showing the efficacy of ARVs as potential HIV prevention tools, the demand for the global limited supply of antirovirals would increase. This will indeed call for concerted efforts between the HIV prevention and treatment field to address the potential challenges this may pose to ARV access for the two fields in the near future. NHVMAS therefore calls on all stakeholders in the field of HIV to work collaboratively as we move the field of HIV prevention into new frontiers. This is a time for joint calls on increased access for HIV treatemtn and prevention within the context of ARV use.  The field can no longer be the same again with the announcement of the results of the iPreX trial. We at NHVMAS will continue to use the result of this trial as well as those of existing and forthcoming trials results as an advocacy tool  to enhance government, partner and community engagement in HIV prevention research. As the World AIDS day
approaches, the world indeed has a calll to make: a call for universal access to HIV prevention and treatment tools and the respect for the rights and dignity of all men irrespective of their sexual orientation.

Understanding Combination Prevention: the way forward for effective HIV prevention

Understanding Combination Prevention: the way forward for effective HIV prevention

This is the reasonable way forward. Unfortunately, this is not a guiding principle applied systematically in HIV prevention, noted Dr Carlos Caceres while given his talk during the plenary session on the 21st of July, 2010.

Combination prevention required that multiple strategies are mutually coordinated and supported to ensure national impact. Currently, most programmes are dispersed, focused on behavioural communication and counselling, poorly disseminated, focused on the short term changes due to the need programe demand for immediate results. These programmes are limited and poorly evaluated and so there was limited understanding of the impact of these programmes. Worsestill, only 7% of total HIV spending was spent on HIV prevention and less than 1% is focused on MARPs.

What is combination prevention: The concept of combination prevention is an analogue to combination treatment. Currently, the concept is used in more than one way (i) combination of 2 or more intervention strategies (ii) combination of diverse strategies to meet the HIV prevention needs of different subpopulations.  (iii) strategic combination of biomedical (Male circumcision, PEP, PMTCT, ARV treatment), behaviour (BCC) and structural interventions  to address key causes of HIV risk and vulnerability in a particular population. The third definitiion is that agreed to by UNAIDS Working Group.

What are structural interventions:  These are interventions that addresses the political, physical and social domains that drives the epidemic. These will mean focusing on aspects of the environment that increases people vulnerability to HIV and decreases access; change in law and regulations; promotion of changes in cultural and social norms, creating a supportive environment; community mobilisation and empowerment; and fostering social inclusion. Good prevention planning includes understanding of human rigths far beyond protecting human rights.

Impact of combination prevention on HIV prevalence: if HIV prevention programming continues status quo, 44 million new cases of HIV will be recorded over the next 25 years. With combination prevention, there will be 29 million new cases. This means that 66% new cases are averted. In addition, structural interventions have borade development effects including addressing poverty and gender inequality. The AVAHAN project in India is an example of such structural interventions with success story amongst many others.

Take home message:  focusing on individuals for prevention is not sufficient. Combination prevention is strategic, evidence informed combining behavioural and biomedical interventions with structural strategies in a human right framwork. This will need a sustained long term response and cannot be implemented in a rigid framework.

Cure for HIV infection must now be major scientific priority, Vienna AIDS conference hears

A cure for HIV infection is scientifically feasible and increasingly necessary, but the goal requires focus and funding, said Sharon Lewin of Monash University in Melbourne, in a keynote address at the opening session of the AIDS 2010 conference.

 Antiretroviral therapy has dramatically reduced illness and increased survival, but people with HIV still do not achieve normal life expectancy relative to the general population. In addition, a growing body of evidence indicates that even very low-level virus contributes to a number of health problems. These problems – which range from cardiovascular and liver disease to neurocognitive impairment and bone loss – are increasingly linked to chronic immune activation and inflammation triggered by persistent virus. "There's some sort of HIV-related problem that's causing people to get sick earlier than they otherwise would have".

The most sensitive tests can find residual HIV in almost everyone infected, including people on effective combination therapy and elite controllers who suppress the virus naturally. "There is no such thing as an undetectable viral load," Lewin added.

The main barriers to curing HIV, are latently infected T-cells, residual viral replication, and anatomical reservoirs (such as the brain, gut and genital tract) that harbour hidden virus.

Most T-cells in the body are resting. HIV mostly infects active CD4 T-cells, which produce new virus but then soon die. In resting cells, by contrast, HIV genetic material is integrated into the host cell's genome where it can remain dormant for a long time, but can "wake up" at any point and reignite viral replication.

Scientists do not fully understand how HIV evades the immune response and establishes latency in resting cells, but a variety of signalling molecules and transcription factors appear to play a role, and thus offer potential targets for intervention.

Intensification of antiretroviral therapy by adding more drugs has not been able to eradicate HIV in multiple studies to date. A more promising approach uses agents such as interleukin 7 (IL-7) to activate resting cells and flush HIV out of hiding. Another strategy uses compounds called histone deacetylase (HDAC) inhibitors to turn on HIV genes.

The experience of one man in Germany, dubbed the 'Berlin patient', offers proof-of-concept that this may be possible. Gero Hütter, who treated the patient, described the case at the IAS pre-conference meeting. The man underwent chemotherapy for leukaemia that destroyed his own immune cells and received bone marrow stem cell transplants from a donor who carried the protective CCR5-delta32 mutation, which makes cells resistance to HIV infection. Within two months after his first transplant the man showed no measurable HIV, despite stopping antiretroviral therapy. Three years later, he still shows no signs of infection.

While widespread bone marrow transplants are not realistic, Lewin acknowledged, this patient tells us that getting rid of latently infected cells and living without antiretroviral treatment is possible, and we need to learn why. Researchers are now pursuing a related approach, using gene therapy to make cells HIV-resistant.

"The international conference in Vienna will not be the conference where we announce a cure," Lewin concluded, "but it will mark the beginning of a future where we seriously prioritise finding a cure."  

For the full report and references, visit: http://www.aidsmap.com/page/1447784

 

NHVMAS statement on CAPRISA 004

Hope on the horizon for HIV prevention in women using topical ARV gels

July 19th 2010, 900pm - The results of the CAPRISA 004 brings so much joy and hope for the many women and advocates in Nigeria and for us at the New HIV Vaccine and Microbicide Advocacy Society: a coalition that has invested years in working towards gingering public support for New HIV Prevention Technology Research and Development in Nigeria. The study showed the ARV containing microbicide gel was 39% effective in reducing a woman’s risk of becoming infected with HIV during sex and 51% effective in preventing genital herpes infections in the women participating in the trial.
The CAPRISA 004 study was conducted in Africa. It was a study of 1% tenofovir - an antiretroviral drug widely used in the treatment of HIV – put in a gel and applied in the vagina 12 hours before and 12 hours after sex. The gel was not expected to be used more than twice in 24 hours. The study recruited 889 women from South Africa. Overall, 98 women out of the 889 became HIV positive during the trial—with 38 in the tenofovir gel group and 60 in the placebo gel group. The study was conducted with high scientific and ethical integrity with evidence of extensive community and national stakeholders engagement and support.
While this study is only a proof of concept study (only shows that ARV based microbicides can indeed prevent sexual transmission of HIV infection), this scientific breakthrough gives us much hope about the VOICE study.
We congratulate the entire CAPRISA team, who worked so hard to make this grounbraking reasearch a success story. We equally appreciate the trial participants, communities, The South African Government and the many other stakeholders around the world for helping to see to the successful conclusion of this important trial.
NHVMAS looks forward to the results of the VOICE study that will tell us more about the efficacy of this ARV based microbicides. We also look forward to hearing about the much needed work with regulatory agencies, product manufacturers and all other stakeholders that need to be mobilised now so as to ensure this product is in the hands of people who most need it in the shortest possible time IF and WHEN the VOICE study confirms this wonderful result.

NHVMAS statement on MDP 301 result:

The result of the MDP 301 announced today was a disappointment for many of us in the New HIV Vaccine and Microbicide Advocacy Society: a coalition that has invested years in working towards gingering public support for New HIV Prevention Technology Research and Development in Nigeria. We had looked forward to the MDP 301 results hoping it will confirm speculations of an effective microbicide following the HPTN 035 results.

 

While the MDP 301 results do show conclusively that 0.5% Pro 2000 does not prevent HIV transmission through vaginal sex, this result have not in anyway diminished the need and importance of microbicide as a possible HIV prevention tool for sexual transmission of HIV infection: the very reason NHVMAS had worked to promote community support for biomedical HIV prevention research.

 

The MDP 301 study is the largest international clinical trial to date and it studied the effectiveness of a preventative HIV gel. Results show no evidence that the vaginal microbicide, PRO 2000, reduces the risk of HIV infection in women as announced by scientists today.

 

This placebo-controlled trial involved 9,385 women at six research centres in four African countries. The study found that the risk of HIV infection in women who were supplied with PRO 2000 gel was not significantly different than in women supplied with placebo gel. Although ineffective in providing protection, PRO 2000 gel itself was safe to use.

 

The report of the trial also shows that trial participants liked the gel and used the gel. Our studies in Nigeria also showed that women engaged in past CS3 and SAVVY trials like the gel. This points to the possibility of women using a gel as a microbicide WHEN a product is finally developed.

 

The results of the MDP 301 study does not reduce in anyway, the need for a product to prevent HIV infection either through anal or vaginal sex. Continuing research into developing a microbicide to be applied topically to prevent sexual transmission of HIV is needed. Development of a product that a woman can control, buy off the counter without prescription, and equally increases sexual pleasure should continue as a research global agenda.

 

We congratulate the MDP team for a successfully conducted trial. We equally appreciate the trial participants, communities and stakeholders in the various countries where these trials were conducted for helping to see to the successful conclusion of this important trial.

 

NHVMAS looks forward to the results of the CAPRISA 004 and the MTN 003 studies that will tell us more about the efficacy of ARV based microbicides. We also look forward to the conduct of future non ARV based microbicide studies while we globally push for universal access for existing and effective HIV prevention tools.

 

NHVMAS celebrates its 7th Anniversary with funfare!!!!

nhvmas celebrated its 7th anniverary on the 4th of June 2010. The celebration also conincided with the opening of its secretariat office located at 51/52 Ijaye Road Ogba, Ikeja Lagos. The ceremony provided a platform to bring together friends and advocates of NHVMAS within and outside Lagos State. It also gave partners and friends an opportunity to familiarize themselves with the vision and mission of the organisation.

NHVMAS was nurtured and hosted for the first seven years of its existence by Journalist Against AIDS (JAAIDS) Nigeria. This was because late Omolou Falobi was a co founding visioneer of the organisation.

The NHVMAS Co-Coordinator, Ms Olayide Akanni gave an account of the seven years of stewardship of the organisation and an assessment of the impact it has made in the field. These include:

l  Integration of NPT advocacy issues into ongoing HIV/AIDS activities

l  Increased community awareness about NPT research and development efforts

l  Increased national visibility of NPT issues in national discussions and HIV/AIDS programming

l  Increased capacity of national IRBs and relevant authorities to review NPT protocols and provide monitoring oversight 

l  Development of a National Standard of Care document

l  Strengthened capacity of Nigerian NPT advocates and researchers.

l  Strengthened collaboration with policymakers and increased focus on NPTs within the national strategic framework

l   NHVMAS serving as a community watchdog

l  Dissemination of NPT clinical trial results

l  Increased collaboration with national, regional and international organizations

l  Facilitating information sharing between stakeholders 

Goodwill messages received from friends and partners from far and near were shared.

A Brief History of New HIV Prevention Research

Early in the epidemic, it was well recognised that the best long-
term hopes for controlling AIDS is the development and widespread
distribution of a safe, effective and affordable vaccine, which
prevents primary infections. Over the last 10 years, funding for HIV
vaccine research has grown astronomically. The 2006 funding for AIDS vaccine development neared the US$1 billion mark, coming in at an estimated US$949 million. This figure reflects a 25 percent increase from 2005. The funders in the field have been The International AIDS Vaccine Initiative (IAVI), Bill & Melinda Gates Foundation, NIH, Europrise. Other players in the field include the Center for HIV- AIDS Vaccine Immunology (CHAVI) and the Gates-funded Collaboration for AIDS Vaccine Discovery (CAVD) which unite major players in the field with unique agreements on data- and sample-sharing, all with the goal of overcoming some of the toughest scientific challenges. For more about the HIV vaccine research field and community related work, visit www.avac.org and read the AVAC Report 2007: Re-Setting the Clock. In the HIV vaccine field there has been one completed phase III trial in Thailand. The product was found not to be able to provide enough protection from HIV infection. Recently, another HIV vaccine trial (Step and Phambili studies which were testing Merck's candidate) was stopped because data from the studies were not showing any promises of the vaccine providing protection for trial participants. There are other HIV vaccine candidates been tested around the world including India, China and South Africa While there is advancement with HIV Vaccine research and development, there is also equal efforts at developing a safe,
effective and affordable microbicides which will allow women – who
most bear the brunt of the epidemic – power to protect themselves
from infection. There types of candidate microbicide that went
through phase III trials (trials that involve 1000s of persons to
test of the product or drug can do what it is expected to do when
used in conditions less than ideal) – Nonoxynol 9, SAVVY, Cellulose
sulphate – were not found to be effective. Results of the Carraguard
studies, another candidate microbicide that underwent phase III
trials in South Africa, would be out in February 2008. We still
await results of the Pro 2000 and Pro2000/Buffer gel studies. We
should hopefully have these by 2008. There are also a lot of new
studies at phase I (studies to show products are safe) and phase II
(studies to show products can do what they are meant to do under
ideal conditions). These new studies are evaluating antiretrovirals
as possible microbicides.

In an effort to ensure that HIV prevention is comprehensive (read
attached slides), many studies are been undertaken to develop more prevention strategies. These include:

• The possible use of antiretrovirals to prevent HIV infection. This
is known as HIV pre exposure prophylaxis. The concept is borrowed
from other pre-exposure prohylaxis like malaria and TB prophylaxis
where the same drugs used for treatment can be used to prevent
infection
• Adult male circumcision which three large scales studies have
shown to help reduce the incidence of HIV infection
• Cervical barriers. However recent studies using the diaphragm
shows that this does not reduce the risk for HIV infection
• Herpes Simplex virus infection treatment
• Evaluation of newer HIV treatment drugs so as to ensure effective
HIV infection management and reduce the rate of transmission of
infection. Currently, 3 new antiretrovirals have been approved for
use by the FDA in the USA.

Any questions?
Moderator

NHVMAS at ICASA 2008

On the 2nd of December 2008, SIDACTION organised a meeting of all its partners engaged in the field of HIV research ethics. Present were organisations from Cameroon, Burkina Faso (3), Cote D'Ivoire,
Republic of Benin, Senegal and Nigeria (2).

During the various presentations of group work and activities, it was
clear that there are some critical gaps in the field: Communities
were increasingly interested in the ethics of conduct of HIV
treatment (ARV and herbal) and prevention research. Yet capacity to
engage in the field was effectively lacking. Also, there was very
little engagement and training of the media in responsible reporting
about HIV (a medium that could be actively engage with research
literacy); and little or nothing was done in most countries on New
HIV Prevention technology issues.

Needs identiifed that should be addressed in the coming months
include:
- capacity building for organisations on ethics
- increasing networking so as to share best practices and lessons
- need to share materials - factsheet and training tools
- training of journalists
- addressing claims and researches on herbal cures for HIV infection
- need for community to serve as 'monitors' of clinical trials in the
field There was a consensus that the region needed to have a network for AIDS service organisations engaged with the ethics of HIV Research. NHVMAS volunteered to host this network and nurture its birth and evolution over the next one year

Morenike Ukpong

New HIV Prevention Technology research: the Nigeria story

Nigeria had in some good ways contributed to the global efforts on
New HIV prevention technology research.

1. Phase I CS3 study: Between the 16th of December 2001 and 4th July
2003, the Centre for Research and Reproductive Realth (CRRH),
Sagamu, Nigeria conducted a phase I (safety and acceptability) study on 6% cellulose sulphate trial as a possible microbicide product. This was part of a multicentre study involving 66 women aged 19 to44. the study noted that the product appear to be safe and well tolerated

2. Acceptability study of Nonoxynol 9: In the late `90s Nigeria,
through the University of Port Harcourt, was engaged in an
acceptability study of nonoxynol 9. The study evaluated the
acceptability of Nonoxynol 9 (N9) foam and film. The study was
aborted abruptly following the results of the UNAIDS multi-centre
effectiveness study that showed that N9 increased the risk of HIV
infection. The wealth of information from that data was not shared

3. Lime juice use as microbicide: A feasibility study on the
possible use of lime as a microbicide was conducted in Nigeria in
October 2003. an expanded study was planned following the outcome of
the Nigerian study. However, strong global evidence pointed to the
potential for lime juice to increase risk of HIV infection and thus
plans for the expanded study was aborted.

4. Phase III SAVVY trial: Nigeria was also engaged in the phase III
SAVVY trial – the testing of a potential microbicide to see if it
was effective. The study was conducted in University College
Hospital, Ibadan and the National Institute of Medical Research,
Lagos between 2004 and 2007. 2140 HIV negative women were enrolled into the study. The research was not able to demonstrate that the product was effective in preventing HIV infection

5. Phase III CS3 trial: Phase III CS3 trials were also conducted in
the Lagos University Teaching Hospital, Lagos and the University of
Port Harcourt between 2004 and 2007. 2160 women were to be enorolled into the study. The study was terminated when the conterpart study conducted in South Africa showed that the product had a potential to increase HIV infection in those that used them

6. Phase IIb oral prophylactic use of tenofovir: Nigeria was also
engaged with the study of the possible use of an antiretroviral
(tenofovir) as a possible drug to prevent HIV infection. Past
studies have shown that this concept – the use of a treatment drug
to prevent infection – is feasible as demonstrated with malaria,
tuberculosis and even with the prevention of mother to child
transmission of HIV. The study in Nigeria was however, halted very
early as the study site could not maintain good clinical practice
standards that was satisfactory.

7. TMC 120 microbicide study: A study was conducted in Nassarawa to measure cross- sectional seroincidence (this means doing a research on a number of HIV-infected people you gather together through some recruitment strategies at a single point in time to estimate how many of these people are newly HIV infected every year). This study conducted with IPM has come to an end. The data has been analysed by the investigator and there may be some interesting information to share with the Nigerian populace that we can learn from. Such information may be pointers to the rate of new HIV infection in some populations in Nassarawa State. IPM would however not go into the next phase of research with the site in Nassarawa State. For IPM, the next stage would be to do a prospective sero-incidence study (this is a study in which people who are not infected are followed up for about a year and you determine how many get HIV infection within that period). IPM has decided to concentrate its work in Southern and Eastern African countries for now. Although IPM is not supporting further incidence studies, there is such a study going on currently in Nigeria through HVTN support for future HIV vaccine studies in Nigeria. IPM may consider doing other forms of study in the country, including possible acceptability studies. Currently, potential difficulties in delivering study products in Nigeria through the custom agency is a considerable barrier that the country needs to address to facilitate study efforts.

8. HIV Vaccine studies: There are also indications that there may be
some new HIV Vaccine related studies that would be conducted in the
near future in Nigeria. The Military Hospital is gearing up for
this. There was a sero-incidence study conducted in Asokoro
Hospital, Abuja for this same reason Nigeria has contributed in so many significant ways to the development of New HIV Prevention Technology. We look forward to the country hosting more studies in the future as this may help answer a few peculiar West African related differences in the global epidemiology of HIV infection.

Update on the aborted HIV Vaccine trial -

On November 13th, Merck & Co. and the HIV Vaccine Trials Network
(HVTN) issued a statement confirming that trial participants in the
STEP trial would be "unblinded" meaning that all volunteers will
learn whether they received the vaccine or the placebo. Study staff
will also learn who received the vaccine and who received the
placebo. The release also stated that volunteers will be urged to
continue with study visits for ongoing risk-reduction counseling and
study-related tests.

The results of the trial showed that there were more infections
among male vaccine recipients than male placebo recipients the
majority of whom were men who have sex with men. (There was one
infection in a heterosexual man enrolled in the trial.) There were
roughly 1100 women enrolled in the trial. There was only one
infection among the women trial participants; this was in the
placebo arm. This is however, not an indication that the vaccine
protected women, since the rates of new infections in women were
very, very low in both arms.

Also, the data from male trial participants showed that new HIV
infection was more pronounced in the group of men whose bodies have
shown some reaction to adenovirus in the past (adenovirus was used
in the development of this tested vaccine). No behavioral or other
factors have been identified to explain the observed difference in
infection rates in vaccine versus placebo groups.

In view of this, it is important and critical for the trial
participants to continue visiting the trial sites so enable the
researchers collect more information. This could provide additional
information about whether those who got infected when using the
tested vaccine was due to the vaccine, to another factor, or simply
to chance.

NHVMAG would continue to bring youb updates as more information
unfolds on the Merck's HIV vaccine trial

Adapted from the Advocates' network report titled 'STEP trial
unblinding: An update'

Future access to Microbicides

The Global Campaign for Microbicides (GCM) - along with others
players in the field of microbicide research and development - is
dedicated not only to accelerating microbicide product development
but also to facilitating the widespread access and use of these
products, once they become available.

Currently, microbicide researchers and advocates are collaborating
with regulatory authorities in some countries to determine what
regulatory requirements a microbicide will have to meet to be
approved for public distribution. These regulatory bodies are
responsible for ensuring that medicines and products are safe,
effective, high quality, and manufactured and stored appropriately;
that health professionals and individuals have appropriate
information; and that promotion and advertising is fair and
balanced. The World Health Organization has convened a series of
regional workshops in Africa and Asia to help educate national
regulatory authorities about microbicide science, product
development and clinical trials. Countries with strong national
regulatory authorities like South Africa and India may be able to
develop regulatory guidance that will be helpful to other countries
with less capacity in the area of evaluating new products.

While all these efforts are ongoing, it is important for all of us
to make sure that public expectations are not raised to unrealistic
levels. The first Microbicides will only be moderately effective and
even these first products may still be several years away from being
approved for use anywhere. The first microbicide will not be
launched in every country simultaneously, or even nationwide in
those countries that are first adopters (most likely countries in
southern Africa).

When, where, how and to whom new drugs become available depends on a number of factors, including the adequacy of the health infrastructure in a country; the political will within the
government and the willingness of the population generally to demand access to the new drugs. NHVMAG is one of the many partner and ally organizations that GCM is working with – in many countries -- on efforts to educate governmental officials and build the public awareness required to make an effective demand on decision-makers to start planning now for how microbicide roll-out will occur and how it will be funded when the first successful products become available.

Scaling up manufacturing capacity to produce a large volume of
microbicides is also critical to ensuring access. It can take 18
months to three years to scale up manufacturing capacity
sufficiently to produce enough of a product for commercial
distribution. So it is important that this process begins early,
possibly even before the clinical trial of the candidate microbicide
is complete because if scale-up doesn't happen, there is a risk of
delaying availability of an effective product. Product developers
and others in the field have begun to develop specific plans to
accelerate access by identifying manufacturers and planning for
manufacturing scale-up now.

Cost, of course, is also a key factor. At least one candidate
microbicide has already been stopped from going into human testing
because it was both too difficult and too expensive to produce. The
researchers decided that it didn't matter whether the product worked
or not because it would be too expensive to be made widely available in poorer parts of the world. So they abandoned work on it.

Even products that are cheap to produce may still not be affordable
to many people who need them. For this reason, work is underway to
develop mechanisms to enable donors and/or governments to subsidize both product purchase and the programs required to deliver them.
Microbicides will be delivered through some mix of public, private,
and social marketing systems. This means that significant
investment also has to be made in strengthening commodity systems for delivering other public health goods, and that the microbicides field will be building on these efforts.

We all know that, historically, most new drugs are introduced first
in developed countries where people and health systems can afford to pay for them. It can often take a decade or more for products
to "trickle down" to developing country markets, and many new drugs and other health innovations never reach people in developing
countries. But advocates and researcher are determined that access to microbicides will follow a different pattern and we have a good
reasons to believe that this is possible. The reason is that
microbicides, unlike most drugs and prevention products, are not
being developed by pharmaceutical companies. The pharmaceutical
companies are driven primarily by the need to make profits. But
most of the organizations working to develop microbicides are not-
for-profit or academic institutions, and are supported by
philanthropic or government funding. So they can afford to be
concerned more with the public health goal of preventing HIV
infection, rather than profit.

The microbicide field, therefore, is primarily focused on ensuring
access to microbicides at an affordable price. Several donor and
product developer require in their contracts that a product can be
made available at low cost in resource poor settings. Microbicide
advocates have already started working with regulators,
manufacturers, governments, health care providers, donors and other civil society actors to do what needs to be done to make sure that people who want to use microbicides – especially those at highest risk of HIV infection -- are able to get them consistently, at a convenient place, at an affordable price, and use them in their
daily lives.

 

Anna Forbes
Deputy Director
Global Campaign for Microbicides
1800 K Street NW, Suite 800
Washington DC , 20006
USA

Advocates in Nigeria disappointed with the Carraguard study result and advocates for continued research efforts on Microbicide

Researchers and Community advocates under the aegis of the New HIV Vaccines and Microbicide Advocacy Society (alias NHVMAG) have expressed disappointment over recently released results that showed that Carraguard, a microbicide candidate undergoing Phase 3 trials   failed to effectively protect women against the risk of HIV infection.Population Council, an international non-profit research institution had tested Carraguard, (a microbicide candidate developed as an odorless, clear gel made from carrageenan, a derivative of seaweed for its) effectiveness in a study conducted between 2004-2007. The study enrolled 6,202 women participants in South Africa. Trial results showed that the product was safe and acceptable to women, but did not reduce their risk of acquiring HIV.Coordinator of NHVMAS, Dr Morenike Ukpong noted that result of the Carraguard study comes as a disappointment to the Nigerian advocates who have continued to wait for good news from the field

We applaud the efforts of the researchers at completing the first large-scale effectiveness microbicide trial. We also appreciate the efforts the researchers are making in ensuring transparent communication with trial participants and with African stakeholders about the trial. We also are aware of the hard work of the trial site staff at ensuring effective community participation in the Carraguard study and this we find exemplary. 

NHVMAS and the community of Nigerian advocates continue to applaud the current partnership observed between researchers and the community: Dr Bode-Law Faleyimu of NHVMAG noted that “this is truly an effort at true stakeholders involvement and teamwork. If this mutual respect, sharing and involvement continues, we believe we will see less futile research and more successful trials in the future

 Ukpong however noted that the disappointment on the part of the advocates only reinforces the need to invest expediently in future microbicide researches.. Quoting Lori Heise of the Global Campaign for Microbicides a leading US based Microbicides Advocacy Organization,  New drug development is always a long term struggle and typically hundreds of product leads fail for every one that succeeds, but discouragement is a luxury we can't afford. Ukpong noted  that “Our  responsibility now is to learn as much as possible from this trial to inform and guide future research, improve future trials, better predict efficacy and understand how best to partner with communities and improve the standard of care offered to participants.

Nigeria had hosted two phase III microbicide trials in the immediate past (SAVVY and CS3). The disappointing results from the two studies has however not dampened the , enthusiasm of researchers and advocates  who are hopeful that other ongoing global  research efforts will yield positive results for a safe, effective and affordable microbicide in the not too distant future . 

 Though the HIV prevalence in Nigeria is decreasing based on the 2001, 2003 and antenatal clinic Sentinel Survey results from the Federal Ministry of Health, the statistics still indicate that women are worse affected by the epidemic.

 Vaginal microbicides which are being developed as a female-initiated method for reducing male-to-female transmission of HIV and possibly other sexually transmitted infections (STI) when used during sex, would therefore be a welcome intervention that will boost the quality of currently existing HIV prevention tools in Nigeria

 The New HIV Vaccine and Microbicide Advocacy Society (alias NHVMAG) is a coalition of stakeholders (advocates, researchers, policy makers, media persons, academia and ethicists) engaged directly and indirectly with New HIV Prevention Technology Research and Development in Nigeria

www.nhv-mag.org

Contact: Morenike Ukpong,

+ 234 803 2459 256;

toyinukpong@yahoo..co.uk

Roundtable proffers ways of respecting the rights of participants in

The state of clinical trials in developing countries came under
scrutiny recently.And the crux of the matter was the right of
volunteers to leave any critical trial without any undue harrassment
or loss of priviledges.

Africa like most developing parts of the world has been the centre
of most clinical trials expecially by western drug
companies.Clinical trials are organised testing of a drug
compound,vaccines or medical device in humans to ensure that the
drug is efficacious and safe.

Volunteerism in clinical trials depicts freedom to leave without any
strings attached.Do clinical trials conducted in developing
countries actually allow such freedoms?

At a media roundtable organized by Journalists Against AIDS (JAAIDS) Nigeria in collaboration with the Nigeria HIV Vaccine & Microbicides Advocacy Group (NHVMAG),Dr. Morenike Ukpong, NHVMAG Coordinator,Ms. Marrie De Cernival of SIDACTION,France and Mr. Azubuike Nwagbogu of the Clinical Trial Unit the National Agency for Foods and Drugs Administration and Control (NAFDAC) bared their minds on various forms of unethical practices with regards to clinical trials.Some of these, according to the speakers, include the poor performance of regulatory bodies tasked with such responsibilities like NAFDAC and the seeming negligence of institutional review boards who are supposed to also monitor trials and other researches being conducted in tertiary institutions across the country. In her presentation, Dr. Ukpong said the freedom to participate in a trial or to opt out of should be part of the fundamental rights of trial participant. She added that participants must also be given full briefing on the trial processes and procedures and comprehension must be assessed before seeking for signing of consent forms.But she lamented that this is oftentimes not so. She tasked the media to be alert and help correct these anomalies. "Just like the media coverage of the court proceedings on the controversies surrounding the Pfizer trials, the media must play its role as an effective watchdog so that government agencies and companies can do what is right." Ms. De Cernival identified poverty in developing countries as a factor that forces participants to remain in trials because they can't afford to pay for such treatments themselves. `In developing countries like Nigeria, participants involved in a clinical trial don't often have the same reasons for participating as that of researchers as many participate primarily because of the free benefits that will accrue to them." This is not the case in developed countries where most trial participants are not interested in free medical care since they can easily access that as provided by the government health plans for citizens.

"In the western world, participants often volunteer for trials
because they are interested in the questions the research aims to
answer. Some also do it because of the benefits the results could
bring to humanity."

Mr. Nwagbogu of NAFDAC, said the agency is working to ensure that
all trials going on in the country are registered with it and are
appropriately approved. He said when applications for approval to
conduct clinical trials are submitted to NAFDAC, its clinical trial
unit first studies the research protocols being presented by the
proponents before making a final judgment on whether to approve or not. He agreed with the other speakers on the significance of informed consent of participants in any research effort, and their freedom to opt out anytime they choose without any backlash from the researchers.

`Overall, before approving any research whatsoever, we make sure the subject of research is something that is important to the nation, is for the greater good of the society and that the interests and
welfare of all trial participants are protected".

The NAFDAC officer admitted that some researches still go on in the
country without NAFDAC's approval.However, such efforts are illegal
while the research findings, no matter how laudable, also wear the
cloak of illegality. He warned that the unscrupulous masterminds
behind such illegalities are also liable to criminal prosecution.

O'Femi Kolawole
Email:ofemi@nigeria-aids.org

No associations between the use of Lemon Juice douching and other STI

Prevalence of HIV and other sexually transmissible infections in relation to lemon or lime juice douching among female sex workers in Jos, Nigeria

Godwin Imade A , G , Atiene Sagay A , Daniel Egah B , Viola Onwuliri C , Matthew Grigg E , Christopher Egbodo A , Tom Thacher D , Malcolm Potts F and Roger Short E

Corresponding author. Email: ereimade@yahoo. co.uk

Abstract

Background: The rates of sexually transmissible infections (STI), including HIV, are high among female sex workers (FSW) in Nigeria and the use of various local vaginal cleansing agents to prevent infection is a common practice. The present study was aimed at determining whether any association exists between current lime or lemon douching and the prevalence of STI and HIV infections among FSW in Jos, Nigeria.

Methods: Consenting FSW who were users of lemon or lime (UL) or non-users (NUL) were recruited for the study between May and September 2006. A structured questionnaire was administered by trained counsellors. Pre-HIV test counselling was done. Participant' s blood samples were tested for HIV and syphilis. Genital examination was done and high vaginal and endocervical samples were collected. The samples obtained were processed for STI using standard laboratory procedures. FSW found with treatable STI received free drugs. HIV results were disclosed after post-test counselling and positive FSW were referred to a HIV/AIDS facility for care, support and antiretroviral therapy.

Results:

A total of 398 FSW (86 UL and 312 NUL) participated in the study. Their mean age was 27.6 ± 7.0 years (range 16 -63 years). HIV prevalence was high for both UL and NUL: 48.8 and 48.2%, respectively (odds ratio 1.0; 95% confidence interval 0.6 -1.2, P = 0.9427). The rates of bacterial vaginosis were not significantly higher in UL (UL 55.8%, NUL 44.0%, odds ratio 1.59, 95% confidence interval 0.96–2.65, P = 0.06). There were no associations between the use of citrus douching and other STI.

Conclusion: There were no significant associations between the prevalence of STI and HIV and lime or lemon juice usage.
 
Sexual Health 5(1) 55-60. Published: 22 February 2008
Full text DOI: 10.1071/SH07047. © CSIRO 2008

Different types of Microbicides

There are different types of microbicides being tested. An analogy is
the detergent. Detergents are meant for laundry, yet there are
differnt types: omo, surf, klin, elephant etc. So is it with
microbicides. There are different microbicides with different names
and different modes of actions.

Below, we would quickly go through what the types of microbicides are
and how they work
Moderator
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Curently there are five groups of Microbicides

1. Detergents also known Surfactants

2. PH modifier also known as body enhancer

3. Polyanions also known as fusion/entry inhibitors

4. ARV based microbicides

5. Unknown mechanisms

1. Examples of detergents
a. Nonoxynol-9 (N9): a detergent present in spermicides and some
vaginal lubricants. Regular and frequent use of the product destroys
the vaginal epithelium

b. SAVVY: Though a surfactant, was found safe but not effective
in preventing HIV infection due to the low HIV incidence in the
regions of study for efficacy to be established

2. Polyanions
a.CS3 also called Ushercell. Found associated with an increased
rate of infection at some of the clinical sites through unknown
mechanisms.

b. Pro 2000 which is a ulphonated polymer. Its inhibits the
attachment of the virus to cells. They are charged polymers. Studies
being conducted by MDP and HPTN use these products. Concentrations of
0.5% is currently being studied in 2 trials

c. Carraguard: Contains Carrageanan which is a product from
seaweed. It binds to the body cells or disease causing organisim
before they can invade and attach. Studies show the product is safe
but not effective in preventing HIV infection. If also does not
prevent pregnancy

3. PH modifier or body defence enhancer
a. Buffer gel: This is a broad spectrum microbicide. Buffer gel
works by keeping the vagina at a low pH (the normal PH) during and
after sex. HIV prefers a basic environment that is, an environment
with a high pH. Studies have shown that HIV is inactivated at a PH
below 4 to 5.8. Buffer gel thus works by boosting the natural body
defence mechanism: increases lactobacilli or rapidly acidifies the
ejaculate

4. ARV Based Microbicide
This group of microbicide are currently being studied. They ARV based
microbicide would not be able to prevent the vagina cells from being
infected BUT should prevent HIV from replicating within the infected
cells. There are a lot of current studies going on at preclinical and
clinical phases. As you follow Microbicide research, you would read
and hear about PMPA (tenofovir based microbicide), UC-781, TMC 120
and MIV 150.

5. Unknown action
Currently, India is studying a herbal preparation for use as
microbicide called Praneem. Its possible mechanism of action is not
known.

Glossary of terms used in microbicides research

Arms: the group in a clinical trial, usually known as the control
group and intervention group. Comparing results from the different
groups enables researchers to determine whether and how well a new
intervention (treatment, vaccine, prevention method, or what ever
is being tested) works. Some studies are designed to test more than
one treatment; these would have more than two arms/group.

Cellulose sulfate (CS) - a gel that was tested as a possible topical
microbicide but in 2007 was found not to be effective. Researchers
thought that CS could potentially block HIV infection (and possibly
other STI infections) by creating a barrier between the virus and
the woman's cells in the vagina, which the virus targets for
infection. This would make it more difficult for the virus to enter
the woman's cells.

Cohort- a defined group of people who are followed over a period of
time during a trial to see if anything changes in their situation
(e.g. a group of HIV negative women could be treated as a cohort).

Coital act - sex involving the penetration of a penis into a vagina.

Control group- the comparison group in a clinical trial. This is the
group of trial participants who do NOT receive the intervention that
is being tested. Depending on the intervention being tested, they
usually either receive no treatment at all, a placebo, or current
treatment in use.

Diaphragm- a small latex silicone dome/cup that covers the cervix
(the lower part of the uterus, or womb, that connects to the
vagina). A diaphragm prevents pregnancy by covering the cervix and
blocking sperm from entering the uterus. It also blocks viruses and
bacteria from entering. Trails have shown that the diaphragms DO NOT prevent women from HIV infection.

Double blind- in a double-blind trial, neither the participants nor
the researchers know which participants are in the control group and
which are the intervention group. This is done to reduce bias
from both researchers and participants. An independent group of
experts who are not researchers in the trial, the Data Safety
Monitoring Board, look at the different points in the trial.

DSMB (Data Safety Monitoring Board)- an independent panel of experts who are not researchers associated with the clinical trial, but who have responsibility to look at the results at different points
during a trial to make sure that it is not ethically necessary
to stop the trial either because the intervention causes greater
risk or is overwhelmingly successful.

Efficacy versus Effectiveness- Efficacy refers to how well an
intervention works under controlled situations (such as in a trial).
Effectiveness refers to how well an intervention works in real life
settings.

Epithelium- layer of cells lining the vagina, the cervix, uterus(and
other body cavities).

Fusion inhibitor- a microbicide that would work by preventing HIV
from attaching to a woman's cells.

Interim data analysis- conducted by the DSMB. Data from the control
and intervention groups of a trial are examined and analysed during
the trial at different points, not just at the end when all the
data is completely collected and the trial is finished. These
interim data analyses are used to make sure that the trial does not
need to be stopped early for safety reasons, or because the
intervention being tested is either causing harm or is shown to be
effective.

Intervention groups- the group of participants receiving the
intervention (e.g. new treatment, vaccine, prevention method) in a
clinical trial.

Microbicide- any compound or substance that can be used to reduce
the ability of a virus or bacteria to infect cells. The microbicide
candidates being developed and tested now for HIV prevention are all topical gels or creams that are inserted into the vagina (or anus),
and that coat the cells lining the reproductive tract.

Second and third generation microbicides- first generation
candidates were the first possible microbicides that were tested but
proven not effective. Second and third generation candidates are
those more recently developed that use and build on the results
obtained from the candidates that didn't work, as well as the new
information and knowledge about HIV. Some of these more recent
microbicide candidates are ARV- based.

Mode of action- how a treatment works. There are several possible
modes of action for microbicides. Some acts as physical barriers,
blocking the virus from entering a woman's cells, others prevent HIV
from entering and infecting the woman's cells, while others
preventing the virus from making copies of it self.

N-9( (nonoxynol-9)- a spermicide (kills sperms to prevent pregnancy) that was tested as a microbicide to prevent HIV infection. It was NOT affective, and its regular use increase women's risk of HIV infection. N-9 works as a surfactant, by breaking up the membrane (outer layer) of the virus, but its regular use also causes
irritation and lesions in the vagina, which made it easier for HIV
to enter the woman's cells.

Oral prophylaxis- taking anti-retroviral pills, either before
sexual exposure (pre-exposure prophylaxis) or after sexual exposure (post-exposure prophylaxis) to HIV.

Pap test (also known as a pap smear)- a medical screening test,
where calls are taken from the cervix and looked at under a
microscope to see if there are any cells that look abnormal. The pap
smear is a way to screen women for early signs of cervical cancer.

Phase 3 clinical trials- randomized clinical/controlled trials on
large groups of participants to look at the efficacy of a new
intervention. Phase 3 trials are begun only after phase 1 and phase
2 trials (which are smaller studies that look at safety, at doses,
and at efficacy) are successfully completed.

Placebo- in a blind or double-blind clinical trial, the control
group receives a placebo. This is not the treatment being tested,
but it looks exactly like the treatment. For typical microbicide
trials, the control group received a gel that looked and was used
the same as the gel given to the intervention group, except that it
did not contain the microbicide. Placebos are used in blinded
clinical trials so that participants and researchers do not know
which participants are in the control group and which are in the
intervention group.

Post- exposure prophylaxis (PEP)- taking oral anti-retroviral
medication for a short period of time after exposure (such as an
accidental needlestick for a health care worker), or possible
exposure to HIV (as in the case of rape). PEP should begin 2-24 hours after the exposure to HIV, and no later than 72 hours. There is evidence that PEP can lower tha risk of HIV infection after exposure.

Pre-exposure prophylaxis (PEP)- taking oral anti-retroviral
medication before HIV exposures. Currently, clinical trials are
being done to determine the efficacy and effectiveness of PEP for HIV prevention.

Randomized clinical/controlled trial- a study to determine whether
and how well a medical intervention (e.g. a drug treatment, a
vaccine, a prevention method, etc.) works. Usually, there are two
groups (also called arms), the control group and the intervention
group. The control group either gets no treatment, the current
standard treatment, or a placebo. The intervention group gets the new intervention. Results from both groups are compared to see whether and how well the intervention works. Participants are placed into the groups randomly (by chance, without knowing which groups they are placed in). There are stages of trials. The first stages test
with small numbers of participants to make sure the intervention is
safe. Later stages enroll more people ad test the intervention's
efficacy.

Sero-conversion- becoming infected with HIV. In clinical trials,
this term is used to refer to people who were HIV negative when they
enrolled in the trial, who became infected during the trial.

STI- sexually transmitted infections.

Surfactant microbicide- a microbicide that works by disrupting or
breaking up the membrane (outer surface) of the HIV virus.

Target cells- type of cell that HIV, or another virus or bacteria,
infects.

Tenofavir - an antiretroviral (ARV) that is currently being tested
in gel format as a possible topical microbicide to prevent HIV
infection.

HIV vaccine- a vaccine that would prevent HIV infection. There is
no effective HIV vaccine at present, but there are several possible
vaccines being developed and tested.

Vaginal lesions- small scrapes of tear in the vaginal, which may be
cellular entry points from HIV.

Kingsley Obom-Egbulem, Delhi.
Nigeria-AIDS.org
February 28,2008

M2008:Do you understand the language of Microbicides research

Cohort. Candidate. Fusion inhibitors. Placebo. Double blind. HPTN
035. Randomization. Surfactant. "Wait a minute! Sounds like some
words coming out of a science fiction movie.

But this is not about science fiction or even a movie. It was the
2008 Microbicides Conference held in New Delhi, India and these were definitely the major language spoken at the conference .You are sure to hear them at any of the sessions for which you had to sit in. Navigating through the microbicides conference was indeed an
interesting process. It's even a challenging process especially for
someone like us who must capture most of the crucial moments and
report all the track A, B and C sessions to a mixed audience of
journalists, PLWH, scientists and even other lay men. Was it
difficult?

Well, to some extent, yes. But when you try to catch up and seems
this researcher or principal investigator (PI) is beginning to speak
in tongues again, you simply switch off, fiddle with your blackberry
and send an sms or email, or take your leave. Some delegates are
even inconsiderate -they just sleep and snore on loudly and care
less what is being presented.

And as soon the speaker is done…they join every one in the usual
round of applaud that greets each presentation no matter
how "senseless" or "boring" it must have been.

While it is right to state that there are some people who had no
business being at the microbicides conference, some of the speakers especially scientist needed to be schooled in the art of
communication. Specifically, the task here is how
to "communicate"(not present) study findings to a mixed audience.

Well Drs. Sharon Hiller and John Mellors actually stood out among
the crowd here. They communicated during their presentations. They
simply spoke in "is and was; A, B and C". Dr. Hillier's presentation
on the Tenofovir study by the Microbicides Trial Network (MTN) and
Dr. Mellor's role play illustrating the science of ARV treatment and
drug resistance was a classic.

I don't know if it's a Pittsburgh tradition (since they are both
from Pittsburgh) but they gave more sense to Judge Edwin Cameron's postulations at M2006 in Cape Town that "Science is useless if it has no social relevance". One can take that further to say that research is useless if it can't be simply communicated to those who would benefit from it.

The microbicides conference is fast becoming a prestigious
conference that enjoys global following and efforts should be made
to attract advocates and supporters who can really discuss the
issues with a lay audience. Understanding the language is therefore
a major step in this direction Just in case one is forced to think that the microbicides conference is not an avenue for laymen to acquire research education, even some doctors I spoke with who were attending the conference for the first time heard Greek and Russian during some of the sessions. Well...for those who believe in self-development and really want to make progress as advocates or communicators who must educate people as we hope for a breakthrough in microbicices research development efforts, here is a glossary of terms used in microbicides research graciously developed by Gender AIDS Forum, South Africa.
www.gaf.org.za

New lessons on HIV infection route

For long, the one way we think that the virus makes iys way through
the vagina soft tissues into the blood stream is though cuts or
lacerations on the wall of the vagina. The cut or laceratiosn create
a path for the virus to move into underlying tissues where it
attaches to CD4 containing cells. However, reports presented by Dr T Hope during the Microbicide 2008
conference showed that even in the absence of cuts, bruises or
lacerations, the virus can move through the cells of the vagina to
deeper tissues through a process called difusion: The virus diffuses
through the layer of cells in the vagina into deeper tissues and
eventually gets attached to CD4 containing cells to establish
infection. Therefore in the absence of bruises, cuts and lacerations
in the vagina, HIV infection can still occur.

The difusion process is easier at the cervix - where there is only a
single layer of cell - compared to the vagina that has several layers
of cells. When there are processes that reduces the thickness of the
cell layer, the time for HIV diffusion into deeper tissues and then
getting attached to CD4 containing cells is shorter.

Also, Dr T Hope showed through laboratory studies that the mucous
produced by the vagina was of great advantage as this traps the virus and reduces the virus ability to move freely. In the presence of
semen however, the vagina PH increases from 4 (an acidic environment) to 7 (an alkaline environment). When the PH of the vagina changes to being alkaline, the mobility of the virus also increases significantly.

For more information, visit the M2008 website

The diaphragm: A Female-initiated barrier methods

Despite the overwhelming need for improved options for devices that can protect a woman from both pregnancy and STIs and the proven
effectiveness of a condom to address this, the female condom is still
poor availability 14 years after product approval. This is chiefly due
to price: in 2006 it was estimated to cost 27 times more than the male condom. This has limited its access even where there is a demand

To achieve a very significant price reduction, use needs to raise the
current uptake from 14 million in 2005 to at least 300 million
worldwide . Current efforts at facilitating a price reduction and
increasing possible uptake includes the development and producting of latex female condoms. India is a known production site for latex female condoms

A number of country programmes are expanding access to female condoms.
A good example is India with the Government proactively engaged with piloting programmes that would increase use and female condom uptake. UNFPA is also developing large-scale projects with a number of partners. Further uptake could be facilitate through NPT clincial trial sights especially those conducting studies on female initiated barriers and microbicide studies. Phase III Microbicide trials engage over 4,000 women in their studies and indirectly have contact with over twice that number. Including female condoms in the prevention package and empowering women to use this condom (appropriate site demonstration of female condom insertion) would help further in its uptake. There has also been interest in the adaptation of the diaphragm (a family planning device which covers the upper part of the vagina known as the cervix) and other cervical barriers for HIV prevention. The cervix is known to have a lot of CD4 cells and thus an active point for HIV ifnection. Protecting the cervix from HIV infection may therefore possibly reduce women's rate of HIV infection However the first major study of the diaphragm failed to show benefit. This was known as the MIRA study which engaged about 5,000 women to use a diaphragm and lubricant, or lubricant alone. The study found no significant difference in HIV incidence between the study arms (those that used the diaphragm and lubricant and those that used lubricant alone). A study of the effectiveness of the diaphragm in preventing sexually transmitted infections (STIs) is however still underway in Madagascar. we do know that STIs increase vulnerability to HIV infection because it causes ulcerations in the skin, vaginal lining or lining of the wrine tract in male thereby creating a route through which the virus could get into the body.

However, not all diaphragms are of the same design, and different
devices may have differing acceptability. A range of products are now
being developed, some designed to be used with a microbicide:

•BufferGel Duet: the Duet is a sombrero-shaped diaphragm which, when lubricated with microbicide, should ensure coverage of the
microbicide in the cervix and the vagina .

•SILCS diaphragm (PATH) is a single-size cervical barrier, designed
to provide the same effectiveness as standard diaphragm, while being easier to supply and provide. Extensive input from women in developed and developing countries ensures the design is comfortable, easy to use, and sleek.

HSV-2 suppression: efforts at preventing HIV infection

HSV-2 infection (HSV-2 infection causes a form of herpes infection)
appears to double or triple the risk of HIV infection by creating
lesions through which the virus can easily enter the body. It also
increases the ability of a person who is infected with the HIV and
HSV-2 to infect others.

About 80-90% of HIV-positive individuals and 50% of HIV-negative
women are HSV-2 infected. Because of the link between HSV 2 infection and HIV infection there has been considerable interest in testing whether HSV-2 suppressive treatment (treatment that would reduce the ability of HSV-2 to multiply in the body) in HIV-negative individuals can reduce their risk of HIV acquisition. Studies are also looking at the possibility of the use of HSV-2 suppressive therapy reducing the ability of HIV positive individuals to infect their sexual partners. Results to date have been disappointing. Two large studies failed to find any protective effect of daily HSV suppression therapy in HIV- negative women or men who have sex with men. A third study HIV- discordant partnerships (one partner is HIV negative and another is HIV positive) where the HIV-positive partner is coinfected with HSV- 2, is ongoing in sub-Saharan Africa and expected to report in February 2009.

Post exposure Prophylaxis (PeP)

Post-exposure prophylaxis (PEP) is a course of anti-HIV medication
that may prevent HIV infection after exposure. It can take HIV
between one and five days to become established in the CD4 T-cells
and lymph nodes after exposure. It is thought that a course of PEP
can act during this time to prevent the virus from taking hold, thus
preventing seroconversion in the person who was exposed.

Currently, the focal emphasis in the use of PEP is amongst health
workers who may be exposed to HIV infection due to needle pricks or other exposures to infected blood and blood products during patient management. There are however, renewed interest in preventing possible HIV infection through rape by the use of PeP. In South Africa, for example, where the incidence of rape is the highest in the world, it has been estimated that more than one million women are raped each year. Rape therefore constitutes a possible HIV infection risk route (when raped by someone who is HIV infected, not only is the semen loaded with HIV virus but the tears from forced penetration also further helps the entry of the virus into the body).

Evidence from studies show that very few cases of HIV transmission
have occurred after PEP, with only six reported transmissions
worldwide in healthcare workers since 1997. Studies of PEP after
sexual exposure have also been promising. For example, a Brazilian
study of gay men found that fewer men became infected after sexual exposure if they took a course of PEP than did a similar group who chose not to take it . A second Brazilian study found no
seroconversions in victims of sexual assault who took PEP within 72
hours of exposure. Similarly, only one of 500 sexual assault victims
in South Africa who were treated within 72 hours of the assault
subsequently developed HIV infection .

Despite this evidence, there are drawbacks to PeP. This include low
uptake due to a number of factors including lack of awareness, and
poor adherence, chiefly due to drug side-effects.

New HIV Prevention technology pipelines - ARV treatment of index partners

There is strong evidence to suggest that antiretroviral treatment
reduces HIV transmission by lowering viral load. Evidence from at
least one study show that current efforts to expand access to
treatment in sub-Saharan have probably resulted in a major reduction in HIV transmission. A three year study in Uganda of antiretroviral treatment coupled with intensive adherence support, behavioural counselling and partner testing led to an estimated 90% reduction in onward HIV transmission, CDC researchers calculated.

An ongoing study, is trying to determine if earlier treatment in
individuals with CD4 counts between 300 and 500 is more likely to
reduce HIV transmission in serodiscordant couples than treatment
initiated according to standard guidelines (the standard guideline
recommendation is that ARV treatment should start when the CD4 count is 200 or less). The study is recruiting in Brazil, India, Thailand, Malawi and Zimbabwe, and expected to report by 2013.

The world awaits the result of this study!

New HIV prevention technology pipelines - the story of PreP

Pre-exposure prophylaxis (PrEP) is the use of antiretrovirals prior
to exposure to HIV to prevent infection. PrEP is intended for use by
people who may be at frequent risk for HIV. This includes people who engage in high-risk behaviour groups such as sex workers, injecting drug users, and people who have unsafe sex with a multiple partners (or whose partners have multiple partners). Currently, no
antiretroviral is yet approved or in use as PrEP. Serodiscordant
couples (sexual stable relationships where a partner is infected
with HIV and the other is not) could also benefit from PreP use.

Much of the data on PrEP result from research conducted in monkeys.
In general though not clearly so, these studies have demonstrated
that PrEP can decrease the risk of infection to varying degree.
these studies have also used different models for testing, making
comparisons of results across studies difficult.

The only human data to date, from a Family Health International
study of tenofovir PrEP in which recruitment was abandoned at two
sites due to a controversy over post-trial care, show no serious
safety concerns during an average of nine months' follow-up.

Four PrEP studies are ongoing and three others are planned for
rollout as of february 2008. The ongoing studies are:
• An efficacy study tenofovir among injection drug users in
Thailand, sponsored by the United States Centers for Disease Control and Prevention (CDC) – expected to report efficacy results in 2009.

• A safety study of tenofovir among men who have sex with men in the United States, also sponsored by the CDC – expected to report safety results 2009.

•An efficacy study of Truvada among heterosexuals in Botswana, also sponsored by the CDC – expected to report efficacy data in 2010.

• An efficacy study of Truvada among men who sex with men in Peru
and Ecuador sponsored by the NIH – expected results in 2010.

The risk of HIV transmission is influenced by a number of biological
and environmental factors, including stage of disease, number of
exposures, viral load in blood and semen, as well as the presence of
other sexually transmitted infections. In addition, studies have
shown that most transmission occurs during the acute stage of
infection or at the late stage of disease, when viral loads are
high. According to studies from serodiscordant couples conducted in
Africa, HIV-positive individuals in the acute stage of infection
were responsible for 43% of all HIV transmissions. Knowing this. HIV
control strategy must be multiprong with a wide range of use options
for all persons affected by epidemic.

New HIV Prevention Technologies - HIV Vaccines

The promise of an effective HIV vaccine has always been just over the horizon, but more than 20 years after the identification of HIV,
vaccines remain far from implementation.

The two large HIV vaccine studies till date have shown no protective
effect.The latest is the Merck's trial which not only showed that the
tested vaccine could not prevent HIV infection but also highlighted
some other findings:

1) The trial participants who received the vaccine showed the highest
risk of HIV infection in individuals who had had adenovirus infection
in the past. Adenoviruses most commonly cause respiratory illness.
they could also cause various other illnesses such as infection of
the GIT, eyes and skin depending on the type. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia and bronchitis

2)the trial also showed that the trial participants who had signs of
adenovirus infection, and were uncircumcised were at four times
greater risk of HIV infection if they received the vaccine compared
to circumcised men who had the adenovirus infection and were in the
placebo group. A vaccine study is still ongoing in Thailand and should be concluded in June 2009. A phase IIb HIV vaccine study known as the PAVE 100 study is still being planned to begin in 2008. While we have dissapintment in the field, more studies are still needed in order to improve understanding of the strengths and limitations of various HIV vaccines designs.

For the future, vaccine approaches would focus more on basic research without precluding clinical research. Currently, investment in
vaccine research comes overwhelmingly from the public sector and
foundations. Only one private company (Merck) has invested more than $10 million annually in vaccine research. Companies cite the current scientific uncertainty and the lack of incentives for conducting
phase II studies and investigating process development as barriers to entry to the field

Prevention of Mother to Child Transmission (PMTCT)

Mother to child transmission remains a major means of HIV
transmission. HIv can be transmitted from the mother to the child
through 3 routes:

1. During pregnancy when the mother goes through trauma that may
cause a tear in the placenta and allow direct contact between the
mother and the child's blood. This should not happen normally. This
route of transmission for HIV infection from mother to child is quite
low

2. At delivery. When delivery is not taken carefully and the child is
exposed to contact with the mother's vaginal fluid which is infected
with the virus, or the mother's blood.ideally, HIV infected pregant
mothers should be slated for caserean section so as to further reduce this possibility

3. After birth through breast milk. This is the most common route of
infection. The breastmilk contains HIV virus. the virus could infect
the child through the gut. the gut contains a lot of CD4 cells and
therefore HIV infection can easily occur in the gut when exposed to
the virus. Often times, HIV infected mothers are advised not to
breastfeed. When they opt too for a number of different reasons, they are advised to breastfeed exclusively (breastfeed the child strictly on breastmilk only) before weaning off the child. Exclusive
breastfeeding is however recommended where replacement infant feeding is not acceptable, feasible, affordable, sustainable and safe

The use of prophylactic Amtiretroviral regimen to reduce the rate of
HIV transmission from mother to child has improved over the past ten years. Current WHO guidelines recommend a short-course regimen ideally consisting of AZT for the mother from week 28 of pregnancy, single dose nevirapine at the onset of labour, and AZT/3TC for 7 days after delivery. The infant should also receive a single dose of nevirapine at delivery, and AZT/3TC for 7 days. Mothers with CD4 cell counts below 350 should be considered for antiretroviral therapy. Despite the proven effectiveness of ARV to reduce rate of Mother to child transmission of HIV infection, mirage of logistic problems prevent the effective use of this innovation include the ineffectiveness of health systems. Less complex regimens are recommended where the health system cannot deliver this level of care, but even the delivery of single-dose nevirapine – the least effective regimen - has posed significant problems for health systems in sub-Saharan Africa. Detailed analysis of programme delivery in Zambia, for example, has shown that only one in three women diagnosed HIV-positive actually took nevirapine at delivery. But then only 30% of woment actually take an HIV test!

No recent analysis of potential technological improvements to PMTCT
programs has been carried out . Ongoing studies are investigating the efficacy of HAART (a ARV treatment regimen consisting of at least 3 drugs) and the safety and efficacy of tenofovir (a type of ARV).

Interpreting the results of HIV prevention trials (2)

Clinical Trial Results Are Valuable. This is because:
1. They can tell us which products are not studying anymore

2. They can point to the kinds of changes that could be made to
improve other clinical trial design

3. They may yield beneficial information about behavioral and
cultural practices that affect HIV transmission and the results we
get from clinical trials; and

4. They provide valuable information about how prevention trials can
be better managed.

Understanding Clinical Trial Results:
Prior to a clinical trial, studies of the product to be tested are
done in the lab and in animals. Small size, medium size and large
size animals are used when testing the product. the right animal is
also used. For example, when testing microbicides, the rabbit
vaginal is used because this is the most sensitive vaginal and if it
does not harm the rabbit vaginal, it may not harm the human vagina.
Doing a microbicide animal study using a donkey may therefore be
wrong.

After animal studies, there are also other phases of studies:
1. Phase I which looks at the safety of the product or drug in very
few people

2. Phase II which looks at the safety of the drug and also tries to
test if the drug can do what it is meant to do in an ideal
condition. This is known as an 'efficacy' study

3. Phase III which looks at the safety of the drug and also tries to
see if the drug or product can do what it is meant to do under
normal conditions

Eg - Ampicillin is an antibiotics that went through animal, phase I,
II and III clinical trials. It was found to be able to treat similar
human infections in animals. It was found safe in phase I studies.
In phase II studies, It was shown to produce good results when taken
every 6 hours for 7 days. In phase III studies, it was shown that if
people miss the every 6 hours once in a while, or use it for less
than 7 days (for 3-5 days) it can still be effective. For this
reasons, the drug went throuh further development.

What is a successful clinical trial:
A clinical trial could end in any of the phases. A phase III trial
could be end because:

1. There is proof that the product can work to prevent HIV infection
e.g. male circumcision

2. That there is no proof that th drug is working e.g. carraguard

3. That the product or drug is causing harm eg making people very
sick or causing more HIV infectione.g. N9

4. When the results are not clear and there is no evidence that it
would be clearer with ontinued study e.g. SAVVY

An HIv prevention Clinical Trial would be considerd Successful if:

1. The research plan is conducted as stated in the study protocol.

2. The study is done using the right method

3. The trial provides further information to the HIV prevention field

4. Trial participants are informed and educated about HIV, the
purpose and outcome of the study.

5. The health of participants is protected

6. Trial is continuously monitored at defined intervals by the right
persons who know what they should be looking out for

7. Participants and the community are engaged with the research
process in an ethical, respectful and efficient manner.

8. The trial participants did not abscond from the trial and so at
least 85% of those that started the trial stayed till the end. This
reduces bias

9. The study results are communicated to participants, their
communities and other stakeholders.

10. A plan to ensure trial participants and or the study community
has access to study products in the case of a positive result.

Interpreting the results of HIV prevention trials (3) - So far so...

In the lats two years, the world had received the results of a
number of HIV prevention trials. Specifically, the following trials
have produced no evidence of effect, or a trend towards harm:

• CONRAD phase III study of cellulose sulphate (UsherCell)
microbicide halted after interim analysis showed higher rate of HIV
infection in UsherCell group (the Family Health International study
of cellulose sulphate, a trial also conducted in Nigeria - was also
halted not because there was harm but due to the fact that the
CONRAD study was stopped).

• MIRA female diaphragm and lubricant study completed, but no
evidence of protective effect.

•HSV-2 suppression therapy which were completed but no evidence of protective effect.

•Population Council phase III study of Carraguard microbicide
completed, but no evidence of protective effect.

•The 0.5% concentration PRO 2000 arm abandoned in the MDP
(Microbicides Development Program) phase III study due to futility

•STEP proof of concept study of Merck's Ad5 HIV vaccine halted after
interim analysis showed lack of protective effect. There was a
tendency towards more harm

Although these studies have not provided a prevention technology for further development, they have demonstrated the ability of multiple sponsors to run large trials of prevention technologies, and
generated important information that will contribute to the design
of future studies.

The only positive results in the past two years from HIV prevention
phase III trials have come from adult male circumcision studies
which shows that circumcision reduces the rate of HIV infection IF
and WHEN the study site heals at least 6 weeks before commensing
sex. The need and importance of healing was evident from the results of a negative signal observed a study of male circumcision in HIV- positive men which showed a trend towards a higher rate of HIV
infection in sexual partners of circumcised men when compared to
partners of men who were not circumcised.

Has the field failed so far?
In the field of drug development, there are evidence to show that
when 10,000 potential drugs are found to possibly work in the
laboratory, it takes an average of 6.5years for ONLY 250 of these
compounds to show that it can actually do something in animals. Of
the 250 compunds, only 5 makes it through to phase III over a 7 year period. And of the five, only 1 makes it for drug approval after a 1.5year period. On the whole, it takes about 15 years to develop a
product even WHEN all the needed information is available.

The HIV prevention field has so far not deviated from the norm of
drug development even moreso in the light of the many unknown that plaques the research field. All trials have informed the planning
and implementation of the next trial in such a way as to improve the
care and protection of trial participants. The field is also more
responsive to community concern.

Has the field failed so far? The moderator lookd forward to your
sharing your views and perception on this. Happy discussion.

Could vaginal microbicides protect men more so than women?

In the July 15, 2008 issue of the Proceedings of the National Academy of Sciences (http://www.pnas.org), Dr. Sally Blower and her colleagues report that mathematical models of real-world use of ARV-based vaginal microbicides predict that men may actually derive greater long-term protection against HIV infection than women. There are a lot of assumptions and unknowns in these models, including questions of microbicide efficacy and adherence, condom use, and drug resistance. But even if ARV-based microbicides turn out to be only partially effective, these models predict that large numbers of at-risk men and women will be protected if these products are widely available and used.
 
One question that remains unanswered, however, is whether the widespread use of an ARV-based microbicide could select for drug resistant strains of HIV. The women enrolled in current or planned trials of ARV-based candidate microbicides likely are at low risk of developing drug resistance. Trial participants will be screened monthly for HIV infection, and will stop using a candidate microbicide immediately if they become infected. These women will be tested frequently to see if they develop drug-resistant virus, and arrangements will be made to ensure they have access to effective drugs. However, as the Blower model suggests, even if an ARV-based candidate microbicide does not seem to select for drug resistant virus during phase II and phase III safety and effectiveness trials, drug resistance could be a long-term problem once the product is widely available and used by women who undergo much more infrequent HIVcounselling and testing. Thus, it will be important to couple the widespread introduction of ARV-based microbicides with increased counselling, education, HIV testing, and drug resistance monitoring for at-risk individuals.
 
To learn more about ARV-based microbicides and HIV drug resistance, see the GCM fact sheets entitled "ARV-based Microbicides: The Promise and The Puzzle" and "Understanding HIV Drug Resistance." These and other basic GCM fact sheets and materials are available for free download at http://www.global-campaign.org/download.htm.

HSV-2 treatment does not reduce the risk of HIV infection.

As we first reported in the April 18, 2008 issue of GC News, although number of studies have shown that herpes simplex virus type 2 (HSV-2) infection is associated with an increased likelihood of acquiring HIV, treating people who have HSV-2 doesn't reduce their risk of HIV infection. In the June 21st issue of the Lancet, Dr. Connie Celum and her colleagues at the University of Washington present the results from the second large-scale clinical trial designed to test whether treating HSV-2 can help prevent HIV infection among high-risk individuals. They found no evidence of a protective effect.
 
In the accompanying editorial, Drs. Ronald Gray and Maria Wawer of Johns Hopkins University argue that these findings call into question current prevention policies that focus on control of sexually transmitted diseases to lower transmission of HIV, stating: "It is time to reassess [this] hypothesis and to adjust prevention policy accordingly."

 

Identified risk factor for HIV infection in women

In a set of recently published articles, Depovera, a hormonal
contracepptive, has been found to increase the risk for HIV
infection in women in real life in women in Kenya, Lesotho, Malawi
an Zimbabwe. The study noted that injectable contraception was
associated with a minor increase in risk of HIV infection. The
reasons are yet to be defined.

The issue for the continued use of Depovera is and individual
woman's issues: a woman has to be able to define her risk for
contracting HIV. If her partner is infected with HIV, she should be
using condoms. The use of hormonal contraception should be in
conjunction with the use of condom (dual protection).

Past studies have also indicated that hormonal contraceptives have
impact on the viral with the viral load being significantly higher
at the early infection period in persons who seroconvert and are
using hormonal contraceptives than those who have established HIV
infection and are using hormonal contraceptive.

Depovera is still legitimately recommended for use in women who are not exposed to HIV, and assuming that the injections used for giving the contraceptive are safe (clean and sterile). However, in
countries where the HIV incidence/prevalence is high, careful
considerations may need to be given to the use of Depovera (and
possibly other Hormonal contraceptives) as a contraception.

References

1. Hormonal contraeption and HIV prevalence in four African
countries: Pauline M. Leclerc, Nicolas Dubois-Colas, Michel Garenne.
Contraception 77 (2008) 371 -376

2. Natural History and Risk Factors Associated with Early and
Established HIV Type 1 Infection among Reproductive-Age Women in Malawi. Johnstone J. Kumwenda, Bonus Makanani, Frank Taulo, Chiwawa Nkhoma, George Kafulafula, Qing Li, Newton Kumwenda, and Taha E. Taha. HIV/AIDS CID 2008:46 (15 June) • 1913

When microbicide clinical trials end: lessons learnt and role of advocates

 Recent experiences with clinical trials closures (either scheduled or unexpected, due to unforeseen circumstances) have elicited a broad range of reactions from civil society groups and the media. When negative, these reactions can have a damaging impact on the conduct of concurrent and future trials.
 
At a Microbicides 2008 workshop, participants examined recent trial closure experiences to determine what supports would help people understand trial closures and their significance at the community level more clearly. They also explored the roles that advocates can play in helping to prevent rumor and mis-communication about trial results and research findings.

The participants at the session agreed that closure of a microbicide trial ahead of schedule is not, in itself, a failure. All past trials had contributed immensely to progress in the field. A balanced public view of trial results can be facilitated by: increasing the sense of community ownership of a trial; highlighting the importance of thorough safety trials for all potential candidates; assuring early and frequent reviews of unblinded trial data by Data Safety and Monitoring Boards (DSMBs); developing effective mechanisms for disseminating the DSMB recommendations within communities; and cultivating transparent and effective stakeholder engagement in the research process. The need to develop a true universal placebo for microbicide trials was also discussed.
 
Advocates have played significant roles in helping to address issues as the trials close. The international, regional and national advocacy communities have helped to assure continued interest in microbicide research, despite setbacks and seemingly negative news from the field. However, their ability to play this role could be greatly strengthened by building advocates’ scientific literacy and capacity. This would better prepared them to: serve as effective CAB members; engage actively with protocol development; and make targeted inputs into decisions about secondary trial endpoints and the standard of care provided at trial sites. The need for a dedicated funding windows to give smaller NGOs much-needed access to funding for capacity-building and other relevant relevant community work was also discussed, as was the need for independent community-level monitors (distinct from DSMBs), to assure transparency.
 
Advocates agrred that they are well situated to identify the steps needed to prevent misinformation which can erode community trust in the research enterprise because they are part of the communities they serve. They can also help to build trust between researchers and civil society stakeholders. Microbicide clinical trials can harness this potential by engaging community advocates early in the various clinical trial design and implementation
 
Morenike Ukpong and Anna Forbes

SAVVY trial result dissemination efforts in Lagos, Nigeria

The SAVVY trial was a phase 3 randomised controlled trail of 1% C31G Microbicides gel. The trial was to assess the effectiness of the gel to prevent HIV infection in women with high risk behaviour. The
trial was conducted in two sites in Nigeria - Lagos and Ibadan. It
The study commenced in 2005 and was concluded in 2007.

The Lagos team organised a trial result dissemination exercise in
two phase. The first effort was to inform stakeholders about the
result of the trial. This meeting held on the 18th of September,
2008. On the 25th of September, 2008, a second meeting was held with trial participants. In all there were

1. 7 stakeholders present representing the State Ministry of Health,
Lagos State Action Committee on AIDS Control and NHVMAS, drug and regulatory agency, the institutional review Board

2. Aproximately 200 past trial participants

Result of study: 2153 were enrolled both in the Lagos and Ibadan arm of the study. 2082 were found eligible for effectiveness of the gel evaluation. 2088 were evaluated for gel safety. 286 of the
participants did not complete the study due to study termination as
a result of the DSMB declaring study futility. 65 participants
discontinued for other reasons. There were seroconversion: 22 in the
SAVVY group and 11 in the Placebo group. No notable safety concerns resulted from the use of SAVVY gel by high risk, HIV negative participants for up to 12 months. No significant differences in frequencies of adverse events were soon between treatment groups. No serious adverse was attributed to product use. No death was related to product use. Two participants discontinued from study due to medical reasons. Also all participants that seroconvert were given adequate counseling and referred for HIV care support service ands ensured future access to ARV through the PEPFAR programme in the institution. There was a 100% registration of all seroconverters on the PEPFAR treatment programme. There was also intensified follow-up those participants referred to PEPFAR to ensure drug use compliance and continuous counseling. The gel was not found effective in preventing HIV infection though many participants reported reduction in STI incidence while using the gel. Condom use was also reported to be high during the study Community Concerns were:

1.  Why were trial participant seperated from other stakeholders
   during result dissemination?
2. Why were other community leaders and gatekeepers not invited for
   the dissmeination exercises moreso they were reached when then research commenced? 
3. After this result, what next? 
4. The PI was requested to conduct post trial analysis of the past trial participants who reported reduced STI incidence due to gel use. An assessment of condom use and STI incidence before, during and after the trial should be studied and reported back to the stakeholder 
5. NAFDAC requested that the PI conduct a proper disposal and
   destruction of all trial samples like the drugs, placebo and condom. 
6. Future trials should incorporate programmes that facilitate
   skills acquisition and poverty reduction intervention. 
7. Other PIs were requested to conduct a result dissemination
   meeting for their stakeholders and trial participants.

Trial participants questions were:

1. The Gel was also associated with allergic reaction like rash
   where ever the gel contacted her skin
2. Any future microbicide studies being planned? 
3. How were they to continue accessing regular HIV testing?
4. How do you address possible HIV infection when a HIV negative person has sex with a HIV positive individual and the condom breaks?
5. Is it true that HIV status cannot be detected before 21days and above?
6. Is it possible to have sex with someone who is HIV positive and you will not be infected? 
7. What is the difference between placebo and SAVVY?
8. What next after this trial? 
9. How can they still have access to condoms? 
10. How are the skills of the trained staff being used post trial? 
11.  Is the SAVVY gel no longer good for use?

All participants left satisfied with NAFDAC noting that the SAVVY study was the first study to ever report protocol violation to their office. This was impressive the official noted.

Reported compiled from reports sent in by Dr Adeiga (PI of the study), Mr
Chibuke Ameachi (NHVMAS collaborator), Ms Augustina Amumuziam (NHVMAS programme officer) and Mr Tubosun Obileye (NHVMAS associate).

NHVMAS members make it to the IRMA Board

Two NHVMAS members made it into the the IRMA SC after an exhaustive process which took several months. The process resulted in the selection of 13 new members bringing the IRMA SC membership to 23.NHVMAS has a long history of  advocating for rectal microbicide research and development knoing very well the high prevalence of unprotected anal sex amongst heterosexuals men and women and MSM. Unprotected anal intercourse is 5 to 80 times more likely to result in HIV transmission compared to unprotected vaginal intercourse. It is imperative that a safe, effective and acceptable rectal microbicides for women and men is developed for use commented Jim Pickett, Chair of IRMA 

We congatulate Kadiri Audu and Lanre Onigbogi on their nominations.

The thrill about the HPTN 035 study

The results of the HPTN 035 provide the first indication that a microbicide gel can at least partially reduce women's risk of HIV. This study represents an important step forward for HIV prevention research. Very briefly, these results are summarized as follows [as described by Sharon Hillier, the MTN PI]:

 

1. PRO 2000 gel (0.5%) was found to be 30 percent effective in preventing HIV infection. While encouraging, this result is not statistically significant. 

 

2. BufferGel was found to have no detectable effect on preventing HIV infection.

 

3. Both gels were found to be safe. This results provides the first signal of the possibility that the microbicide as a concept is feasibile and a topical application of a product in the vagina could actually prevent HIV infection. This is a signal of hope for the field 

As for PRO 2000, more evidence will be needed before we can determine more conclusively its effectiveness. We will eagerly await the results of the MDP 301 trial, which are due by the end of the year. 

 

What would the face of HIV control be in the next 25 years?

• Over the next 25years, there would be increased emphasis on
harnessing host factor to prevent or control HIV infection. Current approaches focus on interfering with viral attachment or
replication. Future efforts would seek to harness anti-viral factors and co-factors to stop or reduce HIV infection. This would provide a pipeline of novel targets for drug development with reduced possibility of resistance. But because HIV attacks innate factors in your body, there may be an increased risk of untoward effects and cellular toxicity with this approach.

• HIV infection has been associated with premature aging. Efforts would be directed at investigating links between aging and HIV.
HIV disease including its impact on premature aging in multiple body systems. Perhaps the HIV field can harness the global interest in prolonging youthfulness to revitalize the global HIV research infrastructure.

• Efforts shall be directed at developing simple test to identify
acute HIV infection. Probably half of all transmission occurs in
the "window period" before people develop antibodies that show up on today's rapid HIV tests. It should be possible to develop a test that has 3 windows: one that indicates no infection, acute infection and seroconvertion. Such a test would allow the world to identify pockets of high transmission and thereby help plan and target prevention efforts better, conduct routine surveillance of incidence rather than prevalence, and counsel people at high risk of transmitting virus to their sexual partners. This appears "doable" but needs to be prioritized.

• There is increasing interest in the possibility of developing
certain ARVs only for prevention. There are currently other
efforts in disease prevention fields where certain drugs are
reserved for prevention versus treatment eg in tuberculosis
management This may possibly be explored for PreP when proven effective