HVTN Regional Meeting – A View from the Outside

This blog is the first in a series of reflections from AVAC staff and members of the Vaccine Advocacy Resource Group (VARG) on the regional meeting of the HIV Vaccine Trials Network (HVTN), which took place in Johannesburg from February 28 to 1 March 2017.

AMP. Licensure. Enrollment targets. Success.

These were a few of the buzz words from the HIV Vaccine Trials Network (HVTN) regional meeting last month. This meeting, the first of three the network will convene in 2017, was held in Johannesburg, highlighting the HVTN’s build out of programs in sub-Saharan Africa—and the significance of an HIV vaccine for this region.

As network meetings go, the audience for this meeting was largely internal; a chance for HVTN core staff and leadership to celebrate key milestones, particularly around the network’s two large efficacy studies—HVTN 702 and the Antibody Mediated Prevention Trials (AMP)—with their clinical site partners.

While advocates are not the primary audience, the HVTN allows us to attend plenaries and other open sessions. AVAC and civil society partners look to these meetings to hear updates, interact with research teams, and continue to build our research literacy and our translation and liaison roles in the HIV vaccine field.

To advocates—both from AVAC and the Vaccine Advocacy Resource Group (VARG), a global team of HIV prevention advocates—looking in from the outside, this meeting underscored the intensity of resources necessary to make clinical trials happen and allowed us to get a sense of how the vaccine field sees itself.

What follows are impressions from AVAC and a few VARG members from our times in meeting rooms—and in hallways.

AMP. The AMP trials are in an exciting place—exceeding enrollment targets across all sites, both in the Americas and Southern Africa, and maintaining high retention and adherence. While we are thrilled about the trials’ current success, and intrigued by passive immunization as a potential prevention strategy, we felt a gap in communication from the trial’s architects about how to situate it in the broader field. AMP is testing a 30-60 minute infusion of an antibody called VRC01 that is administered every two months for just under two years. While there was much discussion about this particular antibody and others in development, it’s not yet clear how researchers will build on the AMP results to deliver a feasible prevention option. We were left with questions about what will happen with VRC01 if the trial shows efficacy, as its dosing schedule makes it hard to imagine as a real world tool. There are also more powerful antibodies and easier methods of administering them that are being explored. We want to be sure that the goals and follow up steps of AMP are well articulated and understood. Watch this space—it is sure to evolve quickly!

HVTN 702. The first vaccine efficacy trial in seven years is now in its 22nd week of enrollment. As 702 sites continue to get started and data from the precursor trials, RV 144 and HVTN 100, continue to provide more clarity on mechanisms of improving immunogenicity, we note a need for cautious optimism. While 702 presents a possibility for moving toward a licensed vaccine, we were a bit concerned about the hopes being raised about this trial, and feel strongly that the messages should convey realistic expectations. Licensure is the ultimate goal, but we have to closely watch, and accurately translate, the data for ourselves and to our communities. If we’ve learned one thing from HIV vaccine research, it’s that we never know what to expect!

PrEP Access. Finally, let’s talk about oral PrEP—researchers certainly did at this meeting. Access to PrEP is (slowly) becoming a reality in trial communities all over the world—and the HVTN, and all trialists, are grappling with how to incorporate PrEP into trials, especially as this context evolves at national, community, and individual levels. As research advocates, we know that the trial context rarely reflects the real world. While we commend the AMP and 702 teams for exploring ways to connect trial participants to mechanisms for PrEP access, we see a necessity for a more rigorous and urgent commitment to link national and local PrEP programs to participants who need and want it.

Note: This is a crucial area that advocates are watching, and where they can and need to help research teams. Without taking PrEP into account and ensuring that communities have input, clinical trials run the risk of being viewed as skirting larger community needs as well as ethical and human rights obligations.

Now that the meeting is wrapped, and we’ve had a couple of weeks to reflect, we’re left with the feeling that the field appears too siloed. The conversations around antibodies and vaccine candidates seem to be happening in isolation from larger dynamism in the field and the very communities where trials are taking place. The rich and rapidly iterating prevention research environment needs an HIV vaccine—and an HIV vaccine needs this exciting environment.

What’s New on AVAC.org

We’ve posted several new resources on AVAC.org that you won’t want to miss.

1) The WHO’s recently released guidance on the use of hormonal contraceptives in women at risk of HIV has prompted a great deal of interest from advocates working in HIV prevention and women’s sexual and reproductive health and rights. We have several new resources that address this complex issue.

2) Advocates continue to work to understand the difference between the US CDC and WHO recommendations about the number of doses that new users of daily oral PrEP need to take to achieve reliable protection. In our webinar, Time to Protection for PrEP, pharmacologists take you through their data. Check out the recording as prelude to our upcoming webinar, Time to Protection Part 2, which follows up on this issue on Tuesday, April 4, 9am US ET / 3pm CET. Tune in to hear representatives from the CDC and WHO review current PrEP guidelines.

3) And on our blog, P-Values, don’t miss Micheal Ighodaro’s post, Building Solidarity Between African American Gay Men and African Gay Men Through PrEP.

Too Little Data and Old Strategy on Prevention for MSM in Africa: Time for change

Despite decades of advances in HIV prevention, HIV continues to burden gay and bisexual men disproportionately, especially younger gay men, and men who have sex with men. This is truly a global health issue—applying equally to the US and to Africa. Vulnerability to HIV exposure is propelled by key structural drivers: antigay stigma laws, poverty and inadequate understanding of how to prevent HIV.

One major difference between the epidemics among men who have sex with men (MSM) in the US vs Africa is the level of information available. In the US, HIV was first diagnosed in gay men and there are decades of data, including on racial disparities. Yet in every report that I read about gay men and HIV in Africa, there is always this disclaimer: “Data on men who have sex with men (MSM) is very limited for sub-Saharan Africa.” This famous line is getting boring!

I remember when I was preparing for my AIDS 2016 plenary presentation and was looking for the most up-to-date data on MSM on the continent. It felt like I was looking for a pin under the ocean! And of course, only a handful of people had information for me, including Chris Beyrer and Linda-Gail Bekker (the immediate past and current presidents of IAS) and Stefan Baral, who I like to call the data guru (Stefan is Associate Professor at John Hopkins) and friends at MSMGF. My good friend Brian Kanyemba (a former fellow of AVAC who now works with the Desmond Tutu HIV Center in South Africa and Advocacy for Prevention of HIV and AIDS-APHA) and I were moved to tears in Zimbabwe during the African AIDS Conference when MSM where not mentioned at all at the opening ceremony by one of our most important allies, Michel Sidibe who is the current Executive Director of UNAIDS.

The very few data that exist give us evidence of emerging HIV epidemics among MSM, often in settings marked by discrimination, homophobia and criminalization. MSM in Africa are understudied, tokenized and then often denied a more meaningful role in advocacy because they are told they lack adequate capacity! High HIV prevalence among MSM in Africa is evidence that prevention strategies are failing to reach this group. Real prevention—prevention that works—demands real engagement with MSM in Africa. This means counting our numbers and supporting the development of leadership among MSM advocates, and sustaining a comprehensive dialogue with the MSM community on the subject of prevention. It’s time to respect gay men in Africa.

What will HIV prevention mean for gay men and other MSM in Africa?

For many of them, that still means using condoms consistently with lubricant that is most times not available! But as we know around the world, HIV prevention has gone far beyond condoms and lubricant, so you might want to ask why Africa isn’t moving along with oral PrEP? In fact, Africa is making some hard-won progress. Activists on the continent are engaging in discussions about HIV prevention through AVAC’s PxROAR Program and more. PxROAR trains US, European and African partners in HIV prevention research and implementation advocacy through mentorship, peer support, networking opportunities and technical and financial assistance.

To go beyond condoms and lubricant, activists are getting involved and learning about prevention research, about PrEP, about cure, about vaccines and long-acting injectables. But is that enough? What else can we do?

It is time to go back the drawing board. We can build on some of the success we’ve had in the past and go further. PEPFAR now has funds directed to key populations (KP), groups such as gay men or sex workers who are considered vulnerable to HIV. These KP funds can be used to build and improve upon programs like PxROAR. We need a targeted effort to inform and work with Africa MSM beyond the known faces. We need to engage with a hidden generation, invite them to conferences like CROI, HIVR4P and IAS, provide direct funding to understand and overcome barriers to HIV prevention for KPs in Africa. If we really want to help, then MSM must participate directly in the design of that help. AVAC is creating new opportunities through the PxROAR Program and other initiatives to inform and work with Africa KP around HIV prevention research, would you join us?

Capsules from CROI 2017

The annual Conference on Retroviruses & Opportunistic Infections (CROI) took place in Seattle from February 13th-16th, offering a dizzying parade of new data. Access available here.

Research Academy for HIV cure investigators

Are you an early to mid-career HIV investigator or clinical scientist, affiliated with or working in collaboration with an institution or university in a resource-limited country? IAS invites you to apply for a fellowship to attend an interactive three-day workshop in South Africa on state-of-the-art HIV cure research, led by Nobel Laureate Françoise Barré-Sinoussi. The IAS Academy will award fellowships to 25-30 outstanding applicants to attend this workshop, with full travel support to participate. Applications deadline: 9 April 2017.

Community Perspectives Survey

Treatment Action Group (TAG) is conducting a survey of community perspectives on provision of Truvada for PrEP in clinical trials of biomedical HIV prevention interventions. We would be very grateful if you would consider completing the survey, which will be anonymous and is online at: http://www.treatmentactiongroup.org/content/community-survey-prep-and-biomedical-prevention-clinical-trials. Deadline: Monday, 20 March 2017, 5:00PM EST.

WHO Updates Guidance on Hormonal Contraception and HIV

Update: AVAC hosted a webinar discussing this topic in further depth. Click here to listen.

Today the World Health Organization issued an updated guidance statement on its recommendations for the use of hormonal contraception by women at high risk of HIV. The update changes the WHO classification of long-acting injectable contraceptives like DMPA (also known as Depo) and NET-EN. WHO states “there continues to be evidence of a possible increased risk of HIV among progestogen-only injectable users.” Based on this possibility and women’s right to informed choice, the WHO has changed the grade for both methods from “use without restriction” to “benefits outweigh theoretical or proven risks”. Click here for a plain language explanation of these grades and to register for a March 10 webinar on this topic. (Update: Recording now available.)

The new guidance is clear that the recommendations are based on women’s right to informed choice in health and that women should have information about this possibility as well as full access to the method of their choice, regardless of their HIV risk.

Here are links to key resources:

What happened?

Since 1996, the WHO has used a grading system for contraceptive methods. This system is called the Medical Eligibility Criteria or MEC. (AVAC has developed a background guide to “grades” and the MEC available here.) The MEC are used to make sure that family planning programs around the world use methods in the same way. Part of the MEC is a grading system that shows how safe each method is and who can use it. Today WHO changed the grade for DMPA and NET-EN.

Both methods are now in the category for which “the benefits outweigh the theoretical or actual risks.” Simply put, this means this method works well and women should feel free to use it, but they should also know about possible risks. In this case, the specific possible risk is that DMPA or NET-EN might increase risk of acquiring HIV. This risk isn’t proven yet and this classification makes it clear that DMPA and NET-EN should be freely available to all women, regardless of HIV risk.

The technical term for the category is MEC 2. A method that can be used without restriction is in the MEC 1 category. Previously DMPA had been classified a MEC 1*. This meant that it could be used safely by anyone but that there were key things for women and health care workers to think about. The MEC 1* classification for DMPA stated that women at high risk of HIV should be told about the uncertainty about this method and HIV risk, and counseled to use condoms.

For the past several years, advocates for women’s sexual and reproductive health and rights have urged action to ensure that all women receive clear information about possible risks and benefits of all contraceptive methods. In many settings, the 1* classification did not change counseling messages about DMPA. Today’s change to a 2 could help ensure that the right to information is fulfilled. As advocates have made clear, this must be in the context of free choice among a range of contraceptive and HIV prevention methods. (Background on this issue is available here.)

Why the change?

The change was recommended by an Expert Review Group convened by the WHO in December. The group looked at available data on the possible connection between the use of hormonal contraceptives and HIV risk in HIV-negative women. This group also looked at information on women’s values and preferences and discussed the ways that the MEC 1* classification had affected what women were told about DMPA and HIV risk. Based on this and other information, the ERG recommended a change to a “2.” The available information suggest a potential increased risk of risk of getting HIV among users of DMPA. The guidance notes that it is not clear whether this risk is real, but also signals that women should know about theoretical risks in their decision making. An independent WHO committee subsequently reviewed and approved the recommendation.

What does it mean?

The change is a strong affirmation of the sexual and reproductive health and rights of women and girls, including the right to information and informed choice. The guidance statement affirms that these rights were “at the core” of the process. It is a positive signal that all women should receive complete information about all of their family planning options. ICW Eastern Africa and other Africa-based civil society groups have documented that the MEC 1* classification did not substantively change the information most women received about Depo.

Women and adolescents need more choices for contraception and HIV prevention at the same clinic. The call for expanded “method mix” (having more contraceptive choices for women) and integration of HIV and sexual and reproductive health programs is not new. But this updated guidance must catalyze action in these key areas. Some women may not want to use DMPA or NET-EN after being counseled. Others may be motivated to take additional HIV prevention steps. Expanded access to a range of long-acting, discrete contraceptive methods is urgently needed, as is expanded access to male and female condoms and oral PrEP at family planning clinics.

Use of DMPA and NET-EN should not be restricted in any way. Any woman who wants to use DMPA or NET-EN should be able to do so, regardless of her HIV risk. Women are fully capable of weighing risks and benefits when given full information. Every woman should have the option she needs and wants and have access to the method as well as comprehensive information about the options.

This guidance affects specific contraceptives and is most relevant for specific parts of the world where injectable use and rates of HIV are both high. There are limited data on many contraceptives and their impact on HIV risk. The ongoing ECHO trial which is a randomized clinical trial designed to assess the impact of DMPA, the Jadelle implant and the copper intrauterine device on HIV risk, as well as pregnancy, side-effects, and long-term acceptability, will provide more information.

In response to the WHO’s revised guidance, ECHO is updating materials and counselling messages for the trial’s participants. ECHO leadership issued a statement reiterating their commitment to fill information gaps on contraceptive and HIV risk in the service of expanding women’s rights.

AVAC will be working with partners in the weeks and months to come to ensure the guidance is operationalized in ways that uphold women’s right to informed choice and access to a wider range of contraception and HIV prevention. We will also continue to work with other stakeholders in the field to understand how the change impacts ongoing research, including the ECHO trial. Please join us for the webinar next Friday, March 10 to learn more and discuss these issues with colleagues. (Recording now available.)

Please let us know your thoughts, questions and information needs and please join us on next week’s call.