Does Sex Have Impact on HIV Prevention Research?

This post was written by Morenike Folayan, Coordinator of the New HIV Vaccine and Microbicide Advocacy Society and member of the CROI Community Liaison Subcommittee.

At the CROI meeting, I seem to be getting signals that sex significantly impacts HIV research design, data interpretation and data use.

First, I learned that availability of tenofovir, the drug used for pre-exposure prophylaxis (PrEP), is 10 to 100 times lower in the vagina tissues than the rectal tissues when taken orally. This therefore implies that the results of PrEP studies conducted to assess HIV transmission through anal sex cannot be automatically translated to imply the results would be pan out the same way when considering vaginal sex. Hmmmm.

Second, I also learned, through informal conversation with those who work in the field for ARV studies, that the reasons many HIV positive men decide to commence ARV use for HIV prevention (treatment as prevention, or TasP) differ from the reasons why women do commence TasP. More men commence TasP out of a sense of protection of their sexual partner—they have a higher sense of responsibility to protect their sexual partner from getting infected. Women on the other hand, commence the use of TasP simply because they are eligible to use the product. I found that very interesting. I think there may be cultural differences in this observation. I doubt if this is the case in Africa. However, like the lessons we learn from CROI, we need evidence. I would like to see a formal study evaluate this social context of TasP use by men and women in different cultural setting.

Third, the iPrEx OLE study showed increase uptake of, and adherence to, PrEP by MSM who were at high risk for HIV infection. In the VOICE study, we see less uptake and adherence by women who were at high risk of HIV infection. Hmmm. Are we starting to see differences in cultural perception of risk or is this truly a sex difference in risk perception?

(Editor’s note: In iPrEx OLE, participants knew that they were being offered an effective prevention tool—it was an open label study; in VOICE, women were counseled that they might be receiving a placebo and that none of the strategies were proven. Understanding how context—research site, clinic, public health program or community center—affects uptake and risk perception is also key.)

Reason for more studies on sex differences in PrEP and TasP use. Maybe conducting studies with transgenders may help address this question. Maybe.

AVAC Report 2014/15: HIV Prevention on the Line

In AVAC Report 2014/15: HIV Prevention on the Line, we take on the current state of global targets for the AIDS response, looking beyond pithy slogans to explore what’s in place and what’s not in terms of targets, resources and action to begin to end the AIDS epidemic. We also provide concise updates and calls to action on key prevention interventions including AIDS vaccines, voluntary medical male circumcision, microbicides, PrEP, and hormonal contraception use and HIV risk.

FACTS 001 and Me

This post was written by Morenike Folayan, Coordinator with the New HIV Vaccine and Microbicide Advocacy Society and member of the CROI Community Liaison Subcommittee. This is the third in a series of community voice posts from CROI 2015. Read the others here and here.

I sat in the meeting room today listening to the results of the FACTS 001 study. I am sure a number of you must have received mails about what the FACTS study was and what the result of the study is.

AVAC states that: FACTS 001 was a trial of a tenofovir-based vaginal microbicide gel to be used before and after sex among young women in South Africa. The study found no effect for vaginal tenofovir gel overall in the trial. While it appeared that most of the participants used the product at some point, there was not enough correct and consistent use in the trial to provide significant levels of protection. There was a trend of modest protection among the small proportion of women in the trial who appeared to have used the product consistently. This was similar to trends seen in previous studies of tenofovir gel among women, but not enough to change the overall outcome of the trial.

I felt extremely disappointed with the results. I ask myself, where do we go from here? How come the FACTS study has no similitude of efficacy? Why does the result of this study not show any complimentary to the CAPRISA 004 study? How can the IRR be 1.0? How can that be if the women used it even some of the time?

I still remain very unclear about the answers to these questions. I think the answers may come as we move into the future. I know some answers may never come also. I hear that repeatedly during this meeting that FACTS, VOICE and Fem-PrEP studies seem to tell us something. I no longer hear that CAPRISA 004 told us something.

As the researchers meet and think about the interpretation of the results, I have one question for them as someone concerned about ethics? Why were study participants recruited from only (that is what it seems to me) from the low socio-economic strata? The PI seem to imply that the study participants were majorly unemployed (she noted this in a response to a question doing the session) and live in shacks and so may have had challenges with using the gel discretely. Microbicides would be used by women from all socioeconomic strata if found effective. Why is it that the livelihood of the young girls recruited from the study a reason to explain poor adherence. Why are studies not designed to fit into the lives of people; rather we expect the lives of people to fit into our research? Why does the recruitment of study participants into these trials not respect the principle of justice?

More questions I guess. I hope to look for answers as I move forward today. I hope my search does not generate more questions also as I face FACTS.

Excitement and Disappointment at CROI as PrEP and Gel Data Break

In the moments leading up to the packed session where new PrEP and gel data were presented, longtime activist and Body editor Julie Davids tweeted that there was an “Oscar-like” atmosphere—referencing the buzz, hum and readiness of the film awards ceremony that completed on Sunday. Unlike the Oscars, which ran three hours and forty minutes, this session was brief—under two hours—and yet the news that it brought will almost certainly change the world. AVAC’s own press release is here. And below is a quick summary of this historic day.

The bottom line from Partners PrEP, PROUD and IPERGAY is that oral PrEP using TDF/FTC provides protection. We knew this already, but the new data add nuance.

  • The Partners Demonstration project among discordant heterosexual couples (where one partner is HIV-positive and one is not) in Kenya and Uganda showed that a program that delivers both PrEP for HIV-negative partners and/or antiretroviral treatment (ART) for HIV-positive partners reduced the risk of HIV infection by 96 percent. These results highlight the potential impact of combining PrEP and ARV treatment to slow the HIV epidemic.
  • The PROUD Study among high risk men who have sex with men (MSM) in the UK showed that daily oral PrEP reduced the risk of HIV infection by 86 percent when delivered in existing public health clinics.
  • IPERGAY, a French study, was the first to examine the efficacy of “event-driven” PrEP – in this case, a three-day dosing strategy involving four pills around the time of sex – among high risk MSM who reported frequent sex. Overall, PrEP reduced the risk of HIV infection by 86 percent in the trial. Based on reported pill use by men in the trial, the regimen that most participants took amounted to at least four doses a week. Previous studies of daily oral PrEP have shown that this may be enough to be protective. However, it is not clear how well the event.

There are a range of press statements, a statement from the US CDC and—starting on 2/25, the webcasts for the sessions will be available. You can find all of those links here.

The PrEP data are terrifically exciting findings insofar as they reinforce that this is a strategy that works when taken as prescribed. In gay men and other men who have sex with men, this means it even works when the instructions for use involve coitally-related dosing. It is really important to remember that the data so far about PrEP, protection and vaginal sex suggest that this type of strategy might not work as well for women. As we discussed in AVAC Report 2014/5, now is the time to invest in an oral PrEP-driven paradigm shift. We made this statement even before the data were out—and now we mean it more than ever.

If anything, emotions ran even higher as the FACTS 001 data were presented. Here, it was news everyone had hoped to avoid.

  • FACTS 001 was a trial of a tenofovir-based vaginal microbicide gel to be used before and after sex among young women in South Africa. FACTS 001 found no effect for 1% vaginal tenofovir gel overall in the trial. While it appeared that most of the participants used the product at some point, there was not enough correct and consistent use in the trial to provide significant levels of protection. There was a trend of modest protection among the small proportion of women in the trial who appeared to have used the product consistently. This was similar to trends seen in previous studies of tenofovir gel among women, but not enough to change the overall outcome of the trial.

Statements and facts sheets from the FACTS consortium, other microbicide stakeholders and CONRAD are all available here.

The world has far more work to do to find additional tools, above and beyond oral PrEP—which should be rolled out to all who want and could benefit from it—to reduce rates of HIV acquisition among women worldwide.

AVAC will be working with partners to convene webinars and in-country discussions in a range of locations to talk through the implications of all of these data. We will announce the schedule in the coming weeks. If you have a specific question or would like support in organizing around these data, please contact us.

Our recently-released AVAC Report: Prevention on the Line provides background and analysis that anticipates and contextualizes these developments.

Press Release

AVAC calls for rapid response to new ARV-based HIV prevention data presented at CROI, including expedited regulatory review, expanded rollout and updated research plans

Contacts

Mitchell Warren, mitchell@avac.org, +1-914-661-1536

Kay Marshall, kay@avac.org, +1-347-249-6375

Seattle, Washington — AVAC today called for a global action plan including targets, resources and research agendas to accelerate access to daily oral pre-exposure prophylaxis (PrEP), with a particular focus on those hardest hit and most underserved, in parallel with continued research to find new prevention options for those most at risk of HIV, especially young African women.

This call comes as new data from a range of antiretroviral (ARV)-based prevention trials provides strong new evidence for how well these prevention options can work. The studies were presented today at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

“Today’s results add to a powerful body of evidence that ARV-based prevention works when it is used correctly and consistently,” said Mitchell Warren, AVAC’s executive director. “But they’re also a reminder that with nearly every prevention option available today, from condoms to PrEP to HIV treatment, correct and consistent use is both critically important and a real challenge.”

“The evidence tells us that we need a two-pronged approach. We should develop ambitious programs to roll out existing, proven options, including daily oral PrEP, around the world to those who can use them. At the same time, we must continue to develop and test newer methods that others at risk will actually want, demand and use,” Warren added.

Three oral PrEP trials presented at CROI provided additional evidence for use of the pill Truvada (TDF/FTC) for prevention. All three trials had very high rates of consistent use and very high rates of protection against HIV infection, specifically:

  • The Partners Demonstration project among discordant heterosexual couples (where one partner is HIV-positive and one is not) in Kenya and Uganda showed that a program that delivers both PrEP for HIV-negative partners and/or antiretroviral treatment (ART) for HIV-positive partners reduced the risk of HIV infection by 96 percent. These results highlight the potential impact of combining PrEP and ARV treatment to slow the HIV epidemic.
  • The PROUD Study among high risk men who have sex with men (MSM) in the UK showed that daily oral PrEP reduced the risk of HIV infection by 86 percent when delivered in existing sexual health clinics.
  • IPERGAY, a French study, was the first to examine the efficacy of “event-driven” PrEP – in this case, a three-day dosing strategy involving four pills around the time of sex – among high risk MSM who reported frequent sex. Overall, PrEP reduced the risk of HIV infection by 86 percent in the trial. Based on reported pill use by men in the trial, the regimen that most participants took amounted to at least four doses a week. Previous studies of daily oral PrEP have shown that this may be enough to be protective. However, it is not clear how well the event-driven regimen would work for men who have less frequent sex than the men in the trial.

“There’s growing demand for daily oral PrEP, and the data suggest that there might be other ways to use this strategy that can provide benefit,” Warren said. “For the sake of clarity and impact, providers, advocates and end users need to work together to develop clear, consistent messages that explain what’s known and not known about levels of protection in the context of different types of sex and different patterns of use.”

Also at CROI, researchers presented results from a trial of a tenofovir-based vaginal microbicide gel to be used before and after sex among young women in South Africa. FACTS 001 found no effect for 1% vaginal tenofovir gel overall in the trial. While it appeared that most of the participants used the product at some point, there was not enough correct and consistent use in the trial to provide significant levels of protection. There was a trend of modest protection among the small proportion of women in the trial who appeared to have used the product consistently. This was similar to trends seen in previous studies of tenofovir gel among women, but not enough to change the overall outcome of the trial.

“The women in the FACTS 001 trial, one of the youngest groups to date in an ARV-based prevention trial, have contributed so much to our understanding of the challenges and complexities of HIV prevention,” Warren said. “The data suggest that these young women did want a product they could use to reduce their risk, but that this particular product did not fit into the realities of their daily lives.”

“Researchers, product developers, advocates and donors must keep working with young women at high risk of HIV to find products that will make sense in their lives. Just as in contraception, we know that we need a range of safe and effective HIV prevention options for different people at risk to choose from at different points in their lives. It is clear that no single option can possibly for work all people all of the time.”

Prior trials have shown that older participants and those in more stable relationships may be more able to use the ARV-based products and dosing regimens that have been tested to date. The median age in the PROUD and IPERGAY studies, for example, was over 30. Couples in the Partners Demonstration project averaged over age 30 and were all in stable relationships. In addition, women who were most able to use the product in previous tenofovir gel trials were older and more likely to be in stable relationships. In contrast, the median age in the FACTS trial was 23, and most participants lived with their parents and were not married.

“Young people may need different options than older women and men, but they cannot afford to wait for products from future trials. Daily oral PrEP can work, right now, for at least some women and men of all ages, and our immediate task is to better understand how to deliver it in a way that can be easily integrated into their lives. Funders should invest now in large-scale targeted implementation of PrEP, linked to national programs, and Gilead (which makes the proven PrEP drug), national regulatory authorities and health ministries should prioritize licensure and rollout,” Warren said.

At the same time, oral PrEP is not the right option for everyone, and continued research into other options is critical. Two efficacy trials of a monthly vaginal ring with a different ARV called dapivirine; phase II trials of two different injectable ARVs, used every two or three months; a phase II daily rectal microbicide gel for MSM and transgender women; ongoing HIV vaccine trials and new passive antibody studies may eventually provide additional options for young people and others at high risk of HIV.

“All of the data presented here at CROI demand action: we need sustained efforts to deliver proven prevention tools, demonstrate and roll out daily oral PrEP and develop long-term solutions such as other microbicides, long-acting ARV and antibody-based prevention, vaccines and cure strategies. Together, we must keep focused on HIV prevention that’s effective, available and meets the varying needs of men and women throughout their lives,” Warren said.

Prevention on the Line, the annual AVAC state of the field report, released last week, outlines many of the steps needed to move this agenda forward. The report in online at www.avac.org/report2014-15.

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About AVAC: Founded in 1995, AVAC is a non-profit organization that uses education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of AIDS vaccines, male circumcision, microbicides, PrEP and other emerging HIV prevention options as part of a comprehensive response to the pandemic.

Women’s Lives on the Line: AVAC’s new report takes on prevention, targets, research and results

AIDS terminology comes and goes. There are short-lived acronyms like MARP (Most-At-Risk Populations) and unpronounceable but universally recognized ones like GFATM. Right now, the way that much of the world is talking about women and girls and their risk of HIV acquisition is as treacherous a field of terms and euphemisms as advocates have seen. Women and their prevention needs are, due to fuzzy rhetoric, left hiding in plain sight.

All of this is going to matter a great deal as the world grapples with the data expected from this week’s Conference on Retroviruses and Opportunistic Infections, which will bring the release of new data on a range of HIV prevention tools including daily oral PrEP in gay men and other men who have sex with men (MSM), serodiscordant couples who were offered PrEP and also offered ART, and PrEP dosed around sex acts (different from the FDA-approved daily Truvada regimen). It will also bring the long-awaited data from the FACTS 001 microbicide trial, which tested a 1% tenofovir gel, applied before and after sex, in South African women.

We don’t know what the data are, but we do know what some of the pitfalls in discussing women’s prevention and treatment needs are. So here are a few points to keep in mind—each of which is expanded upon the recent AVAC Report: Prevention on the Line—as the week unfolds:

Daily oral PrEP is driving a paradigm shift that may mean different things for men and women. The body of evidence on daily oral PrEP shows that it works if taken correctly and consistently. Right now, there is more “real world” evidence of effectiveness in gay men and other MSM—and less is known about how PrEP could be delivered effectively in young women, particularly those who are not in stable partnerships. The data that do exist suggest that women may need to be more adherent to achieve protection against acquisition during vaginal sex, compared to anal sex. So any data on adherence and efficacy from studies in MSM needs to be contextualized—these data will apply to men whose risk is via anal sex and should not be presented as a global indication of what could work for all populations. Check out Part II in AVAC Report 2014/15 for discussion of these nuances and proposals of what global targets for daily oral PrEP could look like, including for young women and adolescent girls.

Many people aren’t saying what they mean when they say “key populations”. The term “key population” came on the scene as MARP shuffled off. It is used to mean many things, and included groups like gay men and other MSM, transgender women, people who inject drug, and sex workers. Sometimes it is used to mean under-served and over-burdened populations, and in this context that includes women and adolescents. Sometimes people say, “key populations and women”. CROI will certainly include information on prevention and treatment services for key populations. Check out our box in AVAC Report 2014/5 on what clarity should look like with this term. Watch closely as data are presented, and keep this question in mind: Where are the women?

Microbicide research is critical to the future of women’s prevention—but no single trial has all the answers. AVAC Report 2013 focused extensively on what recent trials have taught the field about women’s experiences in research. And the upcoming, highly anticipated data from FACTS 001 will provide even more information. Because women’s prevention needs are great, and the current range of available tools is small, each new finding carries enormous weight. Will an efficacy finding trigger a global change in prevention programming? No. Not right away. There are limited quantities of the gel available and much to understand about how it might work in the real world. Will a lack of efficacy signal the end of user-dependent methods? No. Not at all. Each trial has brought a trove of information about how and why women use specific products and how they relate to research, and it’s imperative to act on this information—to listen to women—whatever the outcomes.

Throughout the next few weeks, we’ll cover CROI developments and highlight relevant sections of our recent Report. Bookmark our CROI page and stay tuned!

AVAC Report: HIV Prevention on the Line

AVAC’s annual report of the field, the upcoming CROI meeting and why the coming year is the best and worst of times for HIV prevention

Next week, scientists, advocates and clinicians will gather in Seattle for the Conference on Retroviruses and Opportunistic Infections (CROI), a venerable HIV meeting that often triggers media coverage of the AIDS epidemic and the potential for curbing it and preserving health in people living with HIV.

A range of data is expected from CROI including “late-breaker” abstracts that will showcase data from IPERGAY and PROUD, two trials of oral PrEP using TDF/FTC in gay men and other men who have sex with men in Europe and Canada, and another trial of the microbicide 1% vaginal tenofovir gel in South African women. There will also be data from a PrEP “demonstration project” that provided the strategy in a real-life context for Kenyan and Ugandan couples with one HIV-positive and one HIV-negative partner.
We don’t know what the specific headlines will be, but we can say with confidence that one take-away must be this: The future of HIV prevention is on the line.

In our latest report, AVAC Report 2014/15: Prevention on the Line, we provide a clear agenda for what needs to happen, what’s missing, and why it matters now more than ever before.

Specifically, we argue that:

  • Ambitious prevention goals matter. They can galvanize new action, in part by expanding our sense of what’s possible.
  • But these goals will only work if they’re feasible, well-defined, measurable, and backed by adequate resources and political support. The prevention goals issued so far are inspiring but they don’t yet meet those requirements.
  • As the UNAIDS “Fast Track” for 2020 set aspirational goals, clear short-term targets are also urgently needed. We can’t wait for five years to see if the world is on track to end the AIDS epidemic.
  • The global AIDS response is running at a major financial deficit. New targets will not be met—and may even be irrelevant—if we fail to close a growing global funding gap.

Recent breakthroughs in HIV research have transformed the ability to curb new infections, making it possible to contemplate the end of the global AIDS epidemic. But prevention could be left behind if global leadership fails to make it a priority.

Recently, UNAIDS issued broad goals for HIV testing, ART provision and virologic suppression over the next five years. According to the agency, achieving these “90-90-90” goals would put the world on track to effectively end the AIDS epidemic by 2030.

On the prevention front, UNAIDS seeks to reduce new infections worldwide from 2.1 million in 2013 to 500,000 in 2020, and to eliminate stigma and discrimination. These are ambitious goals and worth aspiring to. But something important is missing from the picture—intervention-specific targets with the specificity, strategy and resources to match. The goal is great. What’s missing is how to get there.

In twenty years, we will have ample hindsight as to whether today’s targets mattered in the quest to end AIDS.

But right now, foresight and focus are urgently required. We’re concerned about whether the targets that have been set are the right ones, how much targets matter—particularly in the context of a global response running at a disastrous funding deficit—and where prevention targets other than those focused on the antiretrovirals in HIV-positive individuals—fit in. We’re also cognizant that targets can turn from audacious to absurd in the blink of an eye if financing, political will and community buy-in are missing.

AVAC works in coalitions in many of the countries hardest hit by the epidemic. Targets that are developed Geneva, Washington DC and other corridors of power can bear little resemblance to the realities of AIDS endemic countries and communities. Where there’s no reality, there’s no relevance. It’s essential that countries have the technical and financial resources to make global targets relevant to national context. Otherwise, the loftiest goals will be ignored.

As we argue in this Report, targets have played a critical role in changing the course of the epidemic. Likewise, a poorly-thought out target can have no impact at all. Right now, it’s critical that targets and tactics are matched to the lofty but achievable goal of bringing an end to AIDS. This is why we’ve devoted the first section of the Report to a look at why targets matter, what targets are missing, and how advocates for a comprehensive response need to work together to ensure smart, strategic targets across the spectrum of prevention options.

We also focus on issues that underpin (and, sometimes, undermine) the ability to meet these targets. We identify three specific areas for action:

  • Align high impact strategies with human rights and realities. Biomedical advances of the past eight years have made it scientifically plausible to talk about ending the epidemic. But plausible doesn’t mean possible. Today some scientists and public health professionals are focused on what can be achieved biomedically—without enough attention to the structural and social contexts in which treatment prevention are delivered. At the same time, some rights-focused partners speak of HIV as being exclusively pill-oriented, suggesting that there isn’t any dynamism or action on the rights-based fronts. It need not be a permanent rift—indeed it cannot be. If science does not get synched up with human rights then then there is little hope of bringing the epidemic to a conclusive end.
  • Invest in an oral PrEP-driven paradigm shift. The world is failing to deliver the most effective interventions with smart strategy and at scale. Daily oral PrEP for HIV prevention is just one example. Global targets for PrEP may be released in the coming months, but there aren’t any plans in place to meet them. Demonstration projects are small and disconnected, funding is limited and policy makers aren’t heeding the growing demand from men and women, including young women in Africa. Now is the time to spend and act to fill these gaps.
  • Demand short-term results on the path to long-term goals. It will be years before the world has an AIDS vaccine, cure strategies, long-acting injectable ARVs or multipurpose prevention technologies that reduce the risk of HIV acquisition and provide contraception. But there’s plenty of activity in clinical trials and basic science for these long-term goals. This activity needs to be aligned with short-term goals that can be used to measure progress and manage expectations.

As AVAC Report goes to press this week and as we prepare for CROI next week, the United States is grappling with profound questions about the ways that the lives of Black men and women are valued under the law. The world is trying to understand how the West African Ebola epidemics got out of control—and how to bring them to an end. And there is continued concern and vigilance over anti-homosexuality laws in Nigeria and the Gambia, and in hate-mongering environments and legislation that endanger LGBT individuals and many other marginalized groups around the world.

These events are not separate from the work that we do to fight AIDS. They embody the issues of racism, inequity, poverty and security that drive the epidemic that must be addressed to end it. In addition to the HIV-specific work laid out in these pages, it is essential to work towards fundamental, lasting and positive change in each of these areas. That will be history-making, indeed.

Press Release

With future of HIV prevention “on the line,” AVAC calls for sharper, bolder strategy to end the epidemic

Contacts

Mitchell Warren, mitchell@avac.org, +1-914-661-1536

Kay Marshall, kay@avac.org, +1-347-249-6375

New York — In a report issued today, AVAC warned that global HIV prevention efforts are in jeopardy due to an absence of strategic targets, resources and specific implementation plans to translate science, slogans and goals into action. The report calls for a robust set of global HIV prevention targets tailored to specific interventions and demands action in several key areas of the global AIDS response, including expanded rollout of daily oral pre-exposure prophylaxis, or PrEP, and alignment of science and human rights-based agendas.

“We’re at a make-or-break moment and the future of HIV prevention is on the line,” said Mitchell Warren, AVAC’s executive director. “Advances in HIV treatment and prevention research have made it possible to contemplate ending the AIDS epidemic in our lifetimes, but that will only happen with smarter planning, increased resources and greater accountability.”

The report was released ahead of the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle (Feb. 23-26), where researchers are expected to present data from several major HIV prevention trials, including studies that could help drive global implementation of PrEP, as well as a key study of a tenofovir-based vaginal gel for women.

Report calls for smart, realistic goals and targets for HIV prevention

Today’s report, entitled Prevention on the Line, takes a close look at global goals for HIV prevention and what it will take to make them a reality. UNAIDS recently adopted the broad goals of reducing new HIV infections worldwide from 2.1 million in 2013 to 500,000 and eliminating stigma and discrimination, both by the year 2020.

Drawing upon lessons from WHO’s “3 x 5” HIV treatment initiative and other case studies, the AVAC Report concludes that ambitious prevention goals are critical – but that they will only work if they’re feasible, well-defined, measurable and supported with adequate resources and political commitment. In the case of the new UNAIDS prevention goals, the report points to a critical need for more specific, interim targets that can be tracked between now and 2020; for better data and monitoring approaches; and for resource allocations that are directly tied to achieving those targets.

“The UNAIDS prevention goals for 2020 are ambitious and inspiring,” said Warren. “But something important is missing from this picture: how to get there. We need a clear path forward, including short-term targets, so we don’t wait five years to see if the world is on track. And new targets won’t be met – and may even be irrelevant – if we fail to close the growing global funding gap for HIV prevention.”

Bold action needed to advance AVAC’s agenda to end AIDS

The report also recommends key actions to advance AVAC’s three-part agenda to end AIDS. First issued in 2011, the agenda calls for sustained efforts to deliver proven prevention tools, demonstrate and roll out new options such as PrEP and develop long-term solutions such as long-acting ARV-based prevention, vaccines and cure strategies.

Key recommendations for 2015 include:

1. Align high-impact HIV prevention with human rights and realities. Research has demonstrated the potential of high-impact prevention strategies, including biomedical approaches like HIV treatment for people living with HIV and voluntary medical male circumcision (VMMC). But these strategies won’t succeed in the real world if we give short shrift to human rights concerns, or if we fail to involve affected communities in designing and implementing prevention programs. Recent experience with treatment and VMMC, in particular, has shown that community buy-in is an essential ingredient of successful rollout and scale-up.

2. Invest now to scale up access to PrEP. Landmark trials have shown that daily oral PrEP is a powerful HIV prevention tool, and studies at next week’s CROI meeting could provide additional support. But the pace of rollout remains far too slow. Demonstration projects are small and disconnected, funding is limited and policy makers are not yet heeding growing demands for access. Funders should invest now in large-scale targeted implementation of PrEP, linked to national programs. National regulatory authorities and health ministries should prioritize licensure and rollout.

3. Accelerate research into long-term solutions. We must sustain and accelerate research on solutions such as an effective AIDS vaccine, long-acting antiretroviral prevention and treatment and a cure. Just like the rest of the AIDS response, this research needs its own short-term targets, aligned to long-term goals.

The new report and related resources, including downloadable graphics, are available now at www.avac.org/report2014-15.

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About AVAC: Founded in 1995, AVAC is a non-profit organization that uses education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of AIDS vaccines, male circumcision, microbicides, PrEP and other emerging HIV prevention options as part of a comprehensive response to the pandemic.

What’s next for HIV Prevention for Women: VOICE-ing the need for FACTS

Today the Microbicide Trials Network (MTN) research team published the final VOICE trial results in the New England Journal of Medicine with findings that add urgency, and perhaps optimism, to the women’s HIV prevention field as it counts the days until the late-February release of data from the FACTS 001 trial of the 1% tenofovir microbicide gel. (There is also a journal commentary entitled Preventing HIV in Women — Still Trying to Find Their VOICE.)

How does a publication of a trial that reported its results two years ago (and ended gel randomization and placebo control three years ago) raise the stakes today? To answer that question, it helps to look back at VOICE’s design and findings to date.

The VOICE trial was a five arm study designed to evaluate daily oral PrEP using TDF/FTC or TDF and vaginal 1% tenofovir gel as HIV prevention tools for women. The randomized, placebo-controlled components of the trial have been done for some time, and the bottom line from the trial was that there was no evidence of efficacy for any of the three interventions tested. Subsequent analyses of samples from participants showed that, even though the majority of women reported high levels of product use, actual adherence was very low. In AVAC Report 2013, we delved in-depth into what this finding meant—and how lack of efficacy in the context of low adherence is a finding that may say as much or more about how women feel about research and health systems as they do about how they feel about the products themselves.

The trial also found that all of the products were well tolerated and safe (to the extent that they were used) and that young women below the age of 25—who were most likely to acquire HIV—were also most likely not to use the products as prescribed.

VOICE D, a protocol launched after the original trial ended, has gathered a wealth of information about motivations for trial participation, misunderstandings in translation and terminology, and other issues that underpinned these findings. AVAC summarized some of these data in our updates from the recent HIV R4P conference.

VOICE is, in many ways, the richest source of information about why women-controlled products weren’t used, and therefore didn’t work, that the field has ever had.

This new publication adds a wrinkle and a glimmer of hope to this version of the VOICE story. A small subset of women provided blood samples that were analyzed for presence of the active ingredients in the experimental arm. Within that subset, an even smaller number had detectable drug in their blood. Researchers compared risk of HIV acquisition between women assigned to the tenfovoir gel arm who had detectable drug at their first quarterly visit (at month three visit) with women assigned to the tenofovir gel arm who had no detectable drug at their first quarterly visit. They found that women who received the gel and used it—per the sample at the three month visit—were 66 percent less likely to acquire HIV than women who did not. This finding was statistically significant. There was no association in similar analyses of women assigned to either the oral TDF or oral TDF/FTC arms.

What does this all mean? Conclusions can’t be drawn from small numbers. But this hint of efficacy sets the stage for the highly-anticipated release of data from the FACTS 001 microbicide trial which tested tenofovir gel in South African women. FACTS 001 used a different dosing regimen than the one used in VOICE, which asked women to use the gel on a daily basis. FACTS 001 asked women to use the gel before and after sex but no more than twice in 24 hours, the same “BAT 24” regimen used in the CAPRISA 004 trial that reported results in 2010 of modest HIV risk reduction across the whole trial, but—like this new data from VOICE—higher effectiveness among those women who used the gel (as determined by presence of tenofovir in blood samples).

As we await these data, advocates can use this new information to help as they continue to think through and prepare messages for a range of scenarios—including the possibility that FACTS 001 might have a finding like VOICE, or that it might not.

Does this type of finding support further evaluations of the same product? Does it suggest moving forward with methods that are less user-dependent? Or does it warrant piloting of the gel as is, to understand whether adherence improves once women know that the product works? It certainly puts all prevention advocates on alert for the FACTS 001 results expected in a few weeks—and adds to the evidence that we will need to put together to map the way forward.

These are just some of the questions that AVAC has been working with partners in several African countries to articulate and prepare to answer in the coming weeks and months. We’ve developed a range of materials and resources to help think through and explain these issues—and look forward to sharing them, thinking aloud and then acting on the data in the coming weeks.

Whatever the outcome from FACTS 001, the VOICE trial—with its almost 6 percent HIV incidence rate—is a reminder of the bottom line for us all: women need prevention tools they can and will use, and the research to find these tools must continue.

New Px Wire: Top Ten Things to Watch in 2015

Welcome to the New Year! Wondering where to put your attention and advocacy energy for the next 12 months? We don’t presume to have all the answers, but our new issue of Px Wire includes a highly selective list of ten issues, events and developments to hold attention and spark actions in 2015 — and beyond.

Want to see the bigger picture? Check out our updated timeline of biomedical HIV prevention research in the centerspread!

Download the latest issue of Px Wire here.