Biomedical HIV Prevention Efficacy Trials, 2014–2016
UNAIDS Report has Bold Vision, Key Messages—But Needs More Precision on HIV Prevention
UNAIDS recently released Fast Track: Ending the AIDS Epidemic by 2030, its report for World AIDS Day (December 1, 2014). Coming nearly two weeks early, the launch was, itself, fast-tracked—and there’s plenty of “we can’t wait” urgency within the pages of the report, starting with the first page (that does more, typographically, with red ribbons than you might believe is possible). It reads:
“We have bent the trajectory of the AIDS epidemic. Now we have five years to break the epidemic or we risk the epidemic springing back even stronger.”
This is on target and a message to convey urgently and with clarity. UNAIDS has its work cut out as an agency that can provide leadership, mobilize resources and push for the shift to community-based service delivery that emerges as one of the core recommendations in the report.
In broad strokes, it’s the right message, with the right vision, at the right time.
But an effective response depends on strategy, details, milestones, resources and specifics—and these are still lacking. This is to be expected, as the UNAIDS Prevention and Non-Discrimination Targets are still in draft form.
The Fast Track World AIDS Day report is clear on what needs to happen to achieve the “90-90-90” goal that calls for 90 percent of people living with HIV to know their status, 90 percent of those to be on antiretroviral therapy (ART) and 90 percent of those to be virologically suppressed by 2020.
It also suggests the components of prevention programming that should also come on line—listing, in various places, male and female condoms, voluntary medical male circumcision, oral pre-exposure prophylaxis (PrEP) for sex workers, men who have sex with men, serodiscordant couples and adolescents, as well as cash transfers for young girls, harm reduction, structural interventions, mass media and behavior change. These prevention elements appear in different subsets throughout the document, leaving some confusion about what, exactly, is essential.
Everything that the UNAIDS report lists is important. But the details of what goes where—which packages, in which places—and what specific terms mean are missing. Cash transfers, for example, can be delivered in a range of ways, with different objectives and different outcomes.
There are also some elements that receive considerably less emphasis. Research and development of more potent ARVs for treatment and prevention, new prevention options for women and other key populations, vaccine and cure strategies, are fundamental to long-term success in “breaking the epidemic”. Within the five-year timeframe set by UNAIDS, there are short-term milestones to set and achieve in each of these areas, even though the ultimate goals may not be reached for many years.
The good news is that this is a solvable problem. We as advocates and activists must use our impatience and collective wisdom to fast-track a process to ensure that clear targets, resources and messages are developed with the same strategy, rigor and urgency as 90-90-90.
AVAC is working with many of our partners to inform this process. This new report adds urgency to this task and clarity to the questions we need to address. As the report stresses, we must all “hold one another accountable for results and make sure no one is left behind.”
In the coming days, AVAC will release “Prevention on the Line”—a briefing paper with core recommendations for effective target-setting across the research-to-rollout continuum. This will summarize core messages and analysis that will be expanded in AVAC Report 2014/15. To receive the Report and other updates in your inbox, please join our Advocates’ Network. Stay tuned—and stay in touch.
The Number of Microbicide Trials Currently Underway
This graphic from AVAC’s Microbicides by the Numbers one-pager shows the number of ongoing microbicide trials in each phase of study.
Why we young women had to resort to putting up the Visible Panty Line
This was originally published on the What’sUpHIV blog that provided live coverage during HIV R4P 2014.
Wednesday was the day we were finally going to be seen and heard: the day that young women from Burundi, South Africa Uganda and Kenya were going to make it all about us. While everyone was in plenary session, we young women plotted to get the most attention when researchers, policy makers and the conference elite walked out of the plenary. Well, we did succeed in catching their collective eye with our visible panty line (VPL)—a clothes line with colourful, sexy lingerie clipped to it. This attracted scores of conference-goers to our corner. But while everyone was curious, not everyone wanted to participate in the activity—which involved writing messages and clipping them to the line. Instead, I watched as the usual suspects wrote messages about issues affecting young women and a few wrote about strategy ideas to improve the young women’s agenda. I was secretly waiting for a researcher to prove me wrong. None did.
This was disappointing because we young women have a lot to say to researchers about the prevention options we want – if only they would listen. For instance, we know that PrEP works. We know young women between the ages 19-24 are most affected in many parts of the world. We also know this group hasn’t been a priority for demonstration projects of PrEP (pre-exposure prophylaxis).
I attended two oral poster presentations on PrEP and microbicides adherence in women. Speaker after speaker explained that they had gathered evidence about how women lie in about product use (aka adherence) trials. I wanted to say to them: “We do not lie as a choice but as a negotiation. Women lie to their partners, to their family, to their community and in trials because we prioritize other people and not themselves. Some of reasons given to explain that “the lies” were – “I did not use the gel because my partner does not like the slipperiness”, “My partner felt it and I had to remove it.” Women who didn’t use a PrEP or microbicide containing an ARV had their samples measured for detectable drug in the blood. They were told their pharmacokinetic levels that indicated no product use. “I beg you to forgive my PK levels,” was one of the responses I observed. Why do we do it?
After all these lies, I rush back to the Advocates Corner and our Visible Panty Line.
Phew, these young women, like our mothers, have submissively found their space on the floor. And then the old women came and the heterosexual man came: again they wanted to help young women. This is what they should do or shouldn’t do. But why don’t they want to listen to the women themselves?
I am livid: they are doing it again! They are gagging young women.
Young women influencing the agenda
This was originally published on the What’sUpHIV blog that provided live coverage during HIV R4P 2014.
In a session on Reproductive hormones and HIV risks, the data showed the need for the ECHO trial, which is a proposed trial that would evaluate three different contraceptive methods (DEPO-provera, the Jadelle implant and the copper IUD) in relation to HIV acquisition. There’s been a lot of debate and discussion about ECHO recently.
The presentation by Christine Wall on hormonal contraception use and the risk of female to male HIV transmission in a Zambian Cohort showed no HIV risk for men in discordant relationships. Elizabeth Byrne’s presentation showed there is some risk of HIV acquisition among injectable progestogen contraceptive (IPC) users in South Africa compared to women who were not using hormonal methods. Byrne also looked at why this might be. She looked at both the natural hormone, progestogen and progestin (the synthetic form of the hormone). Women who are not using hormonal contraceptive and are ‘cycling naturally’—getting their periods—have regular changes in levels of progestogen. IPC users have high levels of progestin due to the contraceptive. In both of these groups of women, elevated hormone was linked to elevated levels of HIV target cells in the cervix.
At the end of this session, Helen Rees, one of the principal investigators of the proposed ECHO trial spoke to the continued need for this trial. She remarked that the data—including presentations from this session—were confusing and/or contradictory, thus the need to get adequate and accurate answers from ECHO as to to whether hormonal contraception increases the risk of HIV. She spoke to the real possibility of the ECHO trial happening noting that it “appeared” it would move forward. This wasn’t a firm confirmation—an important clarification since the session chair suggested that it was certain.
In a lunch-time session at the Advocates Corner, young women advocates and researchers had a dialogue on young women’s access to HIV prevention: past, present and future. Young women from Uganda, Kenya, Burundi, South Africa, Zimbabwe and other regions, raised issues of lack of sexual and reproductive health (SRHR) access, including family planning and information. One participant noted that the young women want to use pre-exposure prophylaxis (PrEP) but it is not available. American advocate Anna Forbes stressed that the initial demonstration projects have not targeted young women even though they are more at risk for HIV infection. Plans are underway for demonstration studies for young women in South Africa and Kenya that will answer if PrEP is feasible among young women. There is therefore a need for young women to start influencing the agenda to address their specific needs.
During a presentation today on PrEP and Microbicides adherence in women, extensive evidence was presented on why some women were not using the products. There was evidence presented on why some women did not use the product. Reasons ranged from having non -supportive partners, fear of possible side effects to peer pressure. The researchers described the impact of discussing “PK” data with participants in VOICE. PK stands for pharmacokinetics, and in this case it refers to the presence of detectable drug in the women’s blood (both the gel and the oral pill in VOICE had tenofovir-based drugs). Adherence to the products was very low in all the VOICE arms—and there was no evidence of protection in any arms.
In a follow up protocol known as VOICE-D, study sites talked to women about their product use, and then also shared the PK data for individual women. Women who said they had adhered very well sometimes changed what they disclosed when their PK data was shared—showing that they had not It was exciting to hear that giving women P.K results initiated discussion on product use. One of the interesting points in the session seemed to be that there is a difference in how long it takes for PrEP to begin to provide protection in women versus men—we’d like to follow up and learn more. Very little was presented on why some women did use the microbicide products in the VOICE trial.
Workshopping Alternative Microbicide Trial Designs
Clinical trials can only achieve their goals if participants use the product. A trial looking at safety or efficacy can’t gather information or draw conclusions if the trial volunteers choose not to follow the protocol—whether it is taking a drug, using a gel or returning for a follow-up injection of a vaccine. When adherence is poor, a potentially effective intervention can be judged to be ineffective—simply because people didn’t use it. Pre-exposure prophylaxis (PrEP) and microbicide trials for HIV prevention have been challenged by low product use among participants.
Given this and the fact that it is becoming more difficult to support the high cost of new drug development, there is a clear need for cost-saving and efficient trial designs to test safety and efficacy. CONRAD, AVAC and the Forum for Collaborative HIV Research joined forces to explore the potential of alternative trial designs. On June 23, 2014, the groups convened a workshop on alternative trial designs for microbicides which generated lively discussion among more than 60 participants. The proceedings from this meeting are now available. Speaker slides are available here.
The workshop generated much lively discussion among its more than 60 participants. A number of possible designs were presented, as described in these proceedings. The meeting co-sponsors have convened a subgroup to look at these designs, with the goal of selecting, revising, and implementing a study design. A peer-reviewed publication summarizing the key points of discussion is also being prepared. AVAC will work with partners to translate these conversations into advocacy priorities and actions—contact us to learn more.
Px Wire July-September 2014, Vol. 7, No. 3
Px Wire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. This issue comes out on the eve of the International AIDS Conference in Melbourne, Australia—and we begin with “AVAC’s Take” on key messages and commitments to look for at and after the meeting. We also call for more PrEP demonstration projects and provide an update of the proposed ECHO trial.
Px Wire October-December 2014, Vol. 7, No. 4
Px Wire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. In this issue, we offer a selective “state of the union” update on various areas of the prevention field—highlighting key developments, messages and areas of work that warrant particular joint attention at the first HIV Research for Prevention (HIV R4P) conference and beyond.
Data and Uncertainty: Understanding updates on hormonal contraceptives and HIV
AIDS 2014 featured analyses of data on the potential relationship between hormonal contraceptives and risk of HIV infection. Researchers Charles Morrison (FHI 360) and Kristin Wall (Emory University), and Mary Lyn Gaffield from the WHO discussed the newest findings and guidance.
Microbicide Clinical Trials Timeline
This graphic from AVAC’s Microbicides by the Numbers one-pager tracks major ongoing and completed microbicide trials. It shows the trials that have provided the current evidence about tenofovir gel as well as planned gel and ring trials.