Disappointed But Not Defeated—Microbicides Advocates Considering the Future

Manju Chatani-Gadi is an AVAC staff member.

Disappointed but not defeated – reflected the mood of many microbicides advocates at the recently concluded AVAC 2015 Partners Forum. At CROI 2015, results were announced from the FACTS 001 study that involved over 2000 mostly young women in South Africa. It found no effect for vaginal tenofovir gel overall in the trial. A month later, at the Partners Forum, many long-time microbicides advocates were still smarting from the results – having put a lot of heart and work into preparing for the results and hoping for success. In that context, participants in a breakout session to discuss the dapivirine vaginal rings studies were a little cautious in discussing how to best prepare for the trial results.

Earlier discussions at the Forum focused on the importance of advocating for women’s access to oral PrEP as a proven intervention. However, the need for a wide array of tools and options for women remains important and the group gathered for this breakout were also interested in non-systemic options for women like vaginal microbicides.

At the breakout session, an IPM colleague shared updates on the ASPIRE (MTN 020) and the RING (IPM 027) studies, reviewed the timeline for study results and plans for follow on trials. Both trials are studying a vaginal ring containing the antiretroviral drug dapivirine that is designed to be inserted into the vagina and remain there for roughly a month. Together, the two ongoing efficacy trials have enrolled over 4500 participants in Malawi, South Africa, Uganda and Zimbabwe. Results are expected in late 2015 or early 2016.

The research teams are planning for success, actively engaging regulators in each country as well as at the global level to discuss the timeline and requirements for licensure, should the results be positive. There are also plans for open-label extension trials to provide former study participants access to the dapivirine ring while it is undergoing regulatory review.

The open-label trials are still research studies that would seek to understand more about the safety and women’s use of the ring, issues important for broader implementation of the ring should it be approved. IPM is also collaborating with key partners to help ensure the ring would then be made available to women in developing countries at a low cost and as soon as possible. The earliest possible regulatory decision would be in 2017 or 2018.

Some participants at the breakout session were interested to know what kinds of adherence measures were being used in the Ring studies. Previous microbicide and PrEP trials – including FACTS 001, VOICE and FEM-PrEP – reported difficulties in participants adhering to trial dosing regimens. They were curious if the Ring study teams were talking to other researchers to learn about how to address adherence issues found in earlier trials. Several participants were concerned on what it would mean for the field if the ring trials did not show positive results, and a few talked about fatigue to disappointing results.

There was animated discussion about whose role it was to prepare for results with policy makers, media and community groups. “Are we doing the work of the trial teams?” one participant asked, “Why aren’t they preparing better?”, “Are we giving false hope?”, and “What if it doesn’t work?” One view that helped to rally the room is that advocates need to be poised to respond to the results – if positive, to advocate for quick passage to licensure and then into the hands of those who most need prevention tools; and if not – to ensure the urgent need for more tools for women does not fall off the radar.

In discussing how to prepare for the ring results expected late 2015 or early 2016, many in the room pointed to existing platforms that could be built on: the in-country mechanisms through which groups prepared for the FACTS 001 results; the ad-hoc groups brought together for the Ring consultations conducted last year by IPM, MTN, AVAC and country partners; and AVAC’s materials and ongoing processes to help prepare advocates for results.

There was a clear call for early planning and for materials that were specific to each country’s context. The group called on the research teams and AVAC to help ensure that advocates had a good understanding of the research to be able to react, and to develop materials and messages. They also called for simple information on results from past trials to be able to refer to. Many advocates in the room committed to have meetings when they got back home to develop more detailed plans.

Cautiously optimistic, advocates and allies left the room still discussing what they learned and felt from FACTS 001 – and how to re-energize for the Ring results.

New Frontiers in HIV Prevention, Treatment and Cure

It’s time to take an active interest in “passive immunization”—a scientific term for an expanding area of research that’s highly relevant to treatment, prevention and cure work. There are trials in humans happening in many regions of the world—and data are beginning to come in that advocates need to understand, analyze and consider.

AVAC hosted a webinar, New Frontiers in HIV Prevention, Treatment and Cure—An advocate’s webinar on passive immunization with a presentation from Dr. Sarah Schlesinger of Rockefeller University. Dr. Schlesinger provided an overview of recent developments across the field including new published data.

Downloads: Slides (PDF) / Audio (MP3) / Animation (Flash)

This webinar was just one in our year-long series, HIV Prevention on the Line. View webinars from the full series here.

The term passive immunization refers to the administration of laboratory-generated antibodies to people. It’s different from vaccine strategies, which teach our bodies how to make antibodies for ourselves.

Dr. Schlesinger is one of the authors of a recent study on passive immunization of a broadly neutralizing antibody (bNAb) called 3BNC117 in both HIV-negative individuals and people living with HIV. This was the first trial in humans of this particular bNAB. At least three other bNABs are currently in early phase clinical trials in humans. This research pipeline is exploring how passive immunization might be used as a treatment (to control HIV in people living with the virus); as a cure (to help clear HIV from viral reservoirs in people living with HIV); and as prevention.

Dr. Schlesinger provided a basic introduction to bNAbs and the ways that they are being studied, and described the work that she and her colleagues have recently published.

Further Reading
The most potent antibodies against HIV are known as broadly neutralizing antibodies—immune responses generated by a handful of people living with HIV. Scientists have analyzed blood from many people living with HIV and in a few have been able to find these bNABs that can block the activity of wide range of strains of HIV. In recent years, scientists have isolated a range of these potent bNAbs and have worked to modify them to make them even more effective, reduce the size of the dose needed for impact, and ensure that they are delivered to the sites of exposure—e.g., the vagina and rectum in the case of sexual exposure—where protection is needed most. Click here to see AVAC’s “Passive Immunization for Busy Advocates” resource, and click here for a recent presentation from Dr. Penny Moore at AVAC’s Advocacy Partners’ Forum.

Passive immunization using bNAbs is one of several strategies that is being explored for both prevention in people who are HIV-negative as well as treatment and cure strategies for people living with HIV. Long-acting injectable ARVs are also being studied in both populations, as are traditional vaccines. Want to understand the differences and the pipelines? Check out the section on injectable prevention in the recently released AVAC Report—and keep an eye out for the next issue of Px Wire, which will feature an extensive discussion of this expanding arena. Also, Richard Jefferys of the Treatment Action Group just published An HIV Cure and a Vaccine within the Next 15 Years?, a terrific overview of key concepts.

New Issue of Px Wire: Action on Oral PrEP and Updates on Antibodies

The new issue of Px Wire, AVAC’s quarterly newsletter on HIV prevention research and implementation, is now available.

Click here to download.

In this issue, you’ll find:

  • Updates on how WHO is approaching broader guidance on oral PrEP—and what advocates think should happen next.
  • A closer look at passive immunization, an expanding area of research referring to the administration of laboratory-generated antibodies. Passive immunization is being explored in people living with HIV in attempts to help control viral replication and/or serve as part of a cure strategy. It is also being explored for HIV prevention.
  • And this issue’s centerspread provides a quick primer on passive immunization with HIV-specific antibodies, long-acting antiretroviral injectables, and preventive vaccines, including a new, informative table reviewing the pipelines in research and development for all three research avenues.

Pre-Exposure Prophylaxis Works—It’s Time to Deliver

A commentary from the leadership of the International AIDS Society on the urgency and relevance of implementing daily oral PrEP as an HIV prevention option for all people at risk of HIV. PrEP isn’t a magic bullet or a strategy that will be everything for everyone, but it’s a key choice to have at the right place at the right time for people in need. This new piece underscores the advocacy case laid out in AVAC’s call for increasing attention to PrEP.

Funding Opportunity: Innovation for HIV vaccine discovery

Purpose: to encourage innovative, high risk, high impact research to identify novel HIV vaccine concepts and targets and answer questions that will aid in the design and development of an effective immunogen to provide long-term safe protection from acquisition of or ongoing infection by HIV. Details at: http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-15-019.html#sthash.4…

Praise for Malawi’s New Focus on HIV Among LGBTI Community

This article first appeared in Erasing 76 Crimes.

Malawi plans to intensify its fight against AIDS in the country’s LGBTI community, winning praise from LGBTI activists for its efforts.

The southeast African country is seeking more than US $388,000 from the Global Fund for Tuberculosis, Malaria and HIV and AIDS for the program, which will provide testing, counseling, treatment, condoms, and advice on how to prevent risky behavior among Malawi’s LGBTI population, estimated to number more than 38,000 people. The intended beneficiaries are primarily men who have sex with men.

“We are commending the Government action to include [gays] in the Global fund proposal for funding,” said Gift Trapence, executive director of the LGBTI-friendly Centre for Development of the People (CEDEP), in an article in the Nyasa Times.

However, Trapence said, more needs to be done.

“It is now a high time to stop being… double faced. Some Government Ministers have been very homophobic by trying to demonise and ostricise sexual minorities while on the other hand the same Government is endorsing HIV policies and proposals to the [Global Fund], seeking funding that also include sexual minorities programmes,” he said.

He called for the repeal of Malawi’s law against same-sex intimacy, which is currently not being enforced while the High Court reviews whether it is constitutional.

“Malawi has progressive policies and on the other hand there are laws that acts as barriers in accessing services for sexual minorities,” Trapence said.

“It is government responsibility in making sure that all Malawians are able to enjoy the right to health [including gays]. That can only be achieved if all Malawians are able to receive non-discriminatory services regardless of race, religious background, region, age, gender, sexual orientation and other status. Hence the need to have laws that protect all people equally regardless of sexual orientation,” he said.

As the Nyasa Times article noted:

In 2009 a gay couple Tiwonge Chimbalanga and Steven Monjeza were arrested and convicted 14 years for publicly wedding.

But former president the late Bingu wa Mutharika pardoned them following an outcry from the international community.

Currently, the High Court reviewing the case of three men who were convicted in 2011 and are serving sentences ranging from 10 to 14 years for practicing homosexuality.

Fighting to Save My Younger Brother’s Life

This article first appeared in the Huffington Post.

Matthew Rose is an HIV and public health advocate based in Washington, DC. He is an adviser at the Young Black Gay Men’s Leadership Initiative and also a member of AVAC’s PxROAR program and Vaccine Advocacy Resource Group.

His life and love are what hold us together in stories and statics. I think of him as my younger brother. Though it is not blood relation, we are related nonetheless. By something more than just the color of our skin but the attraction we feel within. The desire to press our flesh to another men’s flesh in a shared experience, to join with them in a moment of passion and pleasure. This desire marks this younger man as one like me. A younger self that walks his own path but still must navigate the barriers I could not clear away. Having to be unaware of that the map I tried to leave him, the secrets are tried to share are still out of his view.

Research tells us that current rates of HIV infection among a cohort of Black young gay men who are uninfected at age 18 will lead to, approximately 41 percent of them being HIV seropositive by age 40. We need to change that estimation. We have to find a way to stem the tide before the wave crests. Otherwise what hope do we have for generations of young men who are still waking to their sexuality and sexual orientation? Will they too be sentenced to this reality? When will we stop acting as if young people aren’t able to make decisions about what to do with their bodies and decisions about how to protect their bodies?

The breakwater starts by giving them power, choices, knowledge, and access to life changing options.

No state expressly prohibits minors’ access to PrEP or other HIV prevention methods. All jurisdictions expressly allow some minors to consent to medical care for the diagnosis or treatment of STIs, but only eight jurisdictions allow consent to preventive or prophylactic services.

In denying access to PrEP, we are taking away their ability to make choices later. By doing so, we take away an effective option at a time of great need, undercutting their ability to thrive.

On April 10 National Youth HIV Awareness Day, I want folks to remember that in U.S. there was an estimated 21 percent increase in HIV incidence in people aged 13-29 from 2006 to 2009. This increase was driven by a 34 percent increase in HIV incidence in young MSM — the only group to experience a significant increase in incidence in this age range.

We know that youth and young adults are the heart of the today’s epidemic… We also know that youth and young adults can, with the right information, make health decisions about their bodies. We’ve seen what access to contraception for young women has done in terms of engagement in health care. When systems are built to support the efforts of young people, young people use them to make a difference in their lives.

It means we need to better support these young people with options. Making sure they know how to and are able to reach their health potential. Youth and young adults are rising up all over this country to take on the fight to end to this epidemic. Part of supporting that effort means not limiting their options. We need to offer access to a full array of prevention choices and educate our younger brothers. To be empowered to make decisions that will help to end this epidemic.

New Overview of Cure and Vaccine Research from TAG

Richard Jefferys of Treatment Action Group, whose incredibly clear and detailed updates on immunology, virology and pathogensis (a.k.a. what immune system does, how the virus evolves, and what the virus does to the immune system) can be found on the Michael Palm Basic Science Blog, has just published an overview of vaccine and cure research in the TAG newsletter. The piece is a great introduction and update to a critical topic—and to learn more register for an upcoming AVAC webinar.

And for more on cure research, visit our CUREiculum page.

Thailand National Community Advisory Board

Amidst the 80-plus participants at AVAC’s African Partners’ Forum, one face may have stood out more than any other. The one participant from Thailand, an AVAC partner of almost eight years, brought into the room a global perspective and a wealth of research advocacy expertise— that, despite his solitary role and his sometimes quiet demeanor, was palpable throughout the three days.

Udom is a consultant for AVAC working on community engagement in HIV research, and a consultant for the Retrovirology Department of Armed Forces Research Institute of Medical Sciences (AFRIMS) on CAB constitution since 2010. His work at AVAC is to promote community participation in HIV research and Good Participatory Practice (GPP) implementation in the country. Udom is also a member of the National Subcommittee on HIV Vaccine Development and the National Subcommittee on Biomedical HIV Prevention representing the Thai civil society involving in HIV/AIDS. One of the founders of Thailand National Community Advisory Boards (NCAB) on HIV research.

Through the Thai NGO Coalition on AIDS, he has championed the AVAC/UNAIDS Good Participatory Practices—both with research entities and national bodies—and has helped move the dial on stakeholders’ roles in the research process in Thailand. We asked him to share his experiences with the group, in particular development of a National Community Advisory Board. Here are some of his words:

Community participation in HIV research in Thailand can be divided roughly into two stages – before RV144 stage, and RV144 (and beyond) stage. RV144 was the world’s largest HIV vaccine efficacy trial and conducted in Thailand. In Thailand, the concept of community participation in HIV research was rarely mentioned before the RV144 vaccine trial. In the pre-RV144 era, almost all HIV studies in Thailand were treatment, and participants were AIDS patients of the hospitals that also contain research centers. Hence there was no need to engage others besides the patients and their families. Recruitment strategies of that time were word of mouth, banners posted around the hospitals, and pamphlets. For HIV prevention trials such as HIV vaccine, recruitment might involve one or two meetings with villagers of the target area and the local health officers.

Due to its sheer size and the resources that came with it, RV144 inadvertently changed all of these. A few Thai AIDS activists heard about the trial for the first time at an international AIDS conference and were upset for being left out. They thus demanded that the researchers discuss the plan of the trial with the communities living in the target area to prepare them. Attempting to pacify the NGOs, the researchers held several meetings to discuss the ways to move forward with them. Even though both sides agreed that community participation was necessary, they couldn’t agree on the approach or the definition of community. At the same time, the model of the community advisory board (CAB) had been used in the USA for quite some time. The Thai NGOs involved in the meetings seized on the idea of CAB because it allows laypersons to become involved in HIV research, and it was romantically linked to AIDS activism. From then on, CAB became popular among Thai NGOs. Later on, some institutes conducting HIV research in the country also adopted the CAB model to appease Thai AIDS activists (or agitators depending on viewpoint) and to fulfill requirement of the trials’ sponsors. As a result, several CABs were desultorily formed; a couple of CABs were formed even before the responsible research institutes had a study to consult them with.

Unfortunately only the name (of CAB) is adopted. Most CABs in Thailand are not clear about their roles and responsibilities. In the beginning, a couple of CABs existed in name only. There was no meeting, no activity. The selection (of CAB members) process was, and still is, not clearly defined. Criterion for CAB members is ambiguous; some CABs include researchers and members of research teams as bona fide members. In many cases, CAB members were selected based on their deferential attitude toward researchers and staff rather than their qualifications, experiences, or representativeness. The only CAB activity is bimonthly meetings that dedicated mainly to routine update of the trials with very little (or no time) for other discussion. CAB members are not consulted about the meeting agenda ahead of the meeting. The consultations sought from CAB members in the meeting are limited to informed consent forms and, occasionally, educational/communication materials. Most CABs, except one, have never seen protocols of the studies about which they are to give advice. A few CAB members think that the purpose of informed consent is to absolve the researchers from legal responsibility. Many CAB members think that CAB is an additional arm of the research team to recruit people for the trials.

In general CAB members receive no formal or structured training on relevant topics including clinical research and research ethics. Other activities that could improve CAB capability are also lacking such as orientation for new members, mentoring and coaching for new and old members who may benefit from such activities, or reading materials to improve their research knowledge. Regarding capacity building for CAB, the only exception is the youngest CAB formed about 3 years ago by a bio-ethicist working with a few AIDS activists who have CAB experience. This particular CAB has regular CAB training sessions built into their bimonthly CAB meetings as well as annual training workshop and orientation for new members.

The idea of the national CAB was born during the implementation of RV144. A few AIDS activists involved in community engagement of the trial wanted to create an autonomous coordinating CAB to promote cross-learning between existing CABs. After informal discussions with other NGO workers who were CAB members of various research institutes and a meeting to discuss the idea, the national CAB was formed in May 2014. The goal of the National CAB is to promote ethical HIV clinical research through meaningful community participation. The national CAB wants to focus on capacity building in HIV research and research ethics for existing CABs and relevant community members. Members of the national CAB are selected from six HIV CABs in the country. Notwithstanding the name, the national CAB receives no funding from government agency or research institutes.

Almost from the beginning all associated research institutes, except one, are supportive of the national CAB. Only one research institute reckons that the national CAB has to be linked to specific institute/s and formalized by a government body.The national CAB meets every 2 months to discuss various topics that are not specific to trials or institutes but related to wider issues such as the national guidelines on HIV prevention and treatment, ethics of HIV research on vulnerable populations, and the drafts of the national law on human subjects research. The national CAB also conducts activities including GPP training for CABs and community groups, annual NCAB workshop, and training on research ethics for CABs and community groups.

It is too early to gauge the impact of the national CAB. For Thailand, this kind of CAB, an independent and NGO-initiated CAB, is unprecedented. Presently key HIV research institutes and a few HIV-related national bodies are aware of the national CAB and have no object regarding its existence or function. A chairperson of a national sub-committee related to HIV wants the national CAB to serve as additional IRB in parallel with other IRBs in reviewing biomedical HIV prevention trials conducted in Thailand. This is an important challenge for the national CAB considering its tender age and the members’ combined experience. To fulfill the expectation, members of the national CAB have to significantly improve their knowledge on HIV science and research ethics. They also have to expand their involvement horizontally and vertically. It is naïve to expect that this will be easy or encounter no opposition or resistance from other stakeholders. In the end it is left to members of the national CAB to prove that they are relevant and capable of the responsibility.

Rectal Microbicides and Real World Preferences: Discussions at the Partners Forum

Cindra Feuer is an AVAC staff member.

The Partners’ Forum rectal microbicide breakout session could not have come at a more strategic time. By the latter part of this year, the first Phase II rectal microbicide gel study, MTN 017, will come to an end with results expected in early 2016. However, it doesn’t seem likely that this product—which is a reformulated, reduced-glycerin cousin of the 1% tenofovir vaginal gel evaluated in CAPRISA 004, VOICE and, most recently FACTS 001—will move into the Phase III efficacy trial that has been discussed as the next step after MTN 017.

There are many reasons why the Phase III may not happen. There has been anecdotal evidence from MTN-017 and community gel discussion that the gel is not really lube-like (the applicator used to apply the gel means that it ends up in a different part of the rectum than what is lubricated during anal sex). There has also been criticism of the pre-filled applicator (the same one used in the trials of vaginal gel), with some finding it uncomfortable and burdensome to carry around and use. MTN 017 was designed to gather this kind of feedback. These reports are part of what has caused the field to pause. The recent disappointment from the FACTS trial has added to this.

FACTS 001 found that, even though women used the gel about 50 percent of the time, this level of adherence wasn’t high enough to reduce risk of HIV. In the meantime, daily oral PrEP is available today for people at risk of HIV, including the same men and transwomen who might want a rectal microbicide; long-acting injectable ARVs for prevention and treatment are also on the horizon.

The breakout session on rectal microbicides at the AVAC Partners Forum deliberated on new directions, demands and next steps for the rectal microbicide field. Participants felt strongly that there was a need and desire for rectal microbicides even with the advent of oral PrEP. They declared strongly that research should continue.

The second key message took some serious consideration, weighing the urgency of the need and desire for a rectal microbicide against the realities of what is available today, and the promise of the longer-term pipeline. But in the end, the group decided that its recommendation was that anecdotal evidence from MTN 017 should be taken seriously and rectal tenofovir gel shouldn’t move into phase III because of lack of acceptability of the applicator and the fact that the gel does not function like a lubricant—meaning two products would still need to be used. The group heard a description of Microbicide Trials Network’s (MTN) proposed Phase II Adonis Study design comparing different strategies for delivering a rectal microbicide, looking beyond the current applicator.

The group also weighed in on longer-term efforts and agreed on the need to: Keep a robust pipeline moving through development, including dapivirine gel Phase I to start this year; douche microbicides; and preclinical compounds especially Griffithsin, a non-ARV microibicide.

And, of course, the group was all in favor of continuing rectal microbicide research in South Africa, one of the homes to MTN 017, the first rectal gel study on the continent.

There was recognition for a revived African advocates voice in support of these demands on the IRMA listserv, which is closely followed by a range of researchers and leaders in the field, including scientists at the MTN and NIH—as well as PrEP, vaccine and all-around prevention researcher Linda-Gail Bekker of the South African Desmond Tutu HIV Foundation who declared at the Forum, “If you aren’t following IRMA, you haven’t lived!”