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.

 

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

 

  1. 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