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.

HIV R4P Conference Day 3 Snapshot

Welcome to Day 3 of the HIV R4P conference daily round-up! As we’ve been doing all week, this update offers a selective, whirlwind tour through some of the day’s sessions—all of which are available via webcast 24 hours after they took place. There’s lots more information and insight in the conference’s liveblog and the Twitter feed #HIVR4P.

Morning Plenaries 
This morning’s plenary session brought three presentations on mucosal immunology. Mucosa, including the linings of the vagina and the rectum, are the site of sexual transmission. But these locations—like sex itself—are simultaneously easy to talk about and difficult to describe with precision. While it’s clear HIV acquisition via sex starts at the mucosa, there are still lots of questions about how infection starts—in what cells—and how it progresses from the localized site(s) of entry to a disseminated infection in which virus is found in the blood and throughout the body. 

Jake Estes (Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research) provided a vivid look—complete with 3-D imaging—at the path of dissemination using a non-human primate model. Estes and his collaborators used viral inoculum that had been carefully selected for non-inflammatory studies. (Interesting fact for the lay person—the stuff other than the virus that is in a viral challenge can change the mucosa in an animal experiment.) His presentation maps what was found in different animals—a localized, genital tract infection that may move out into the body via the lymphatic system. 

Next, Jo-Ann Passmore (University of Cape Town, National Health Laboratory Service, and CAPRISA) presented on some of the factors in the genital tract that appear to make HIV infection more likely. Sexual transmission via vaginal sex is relatively inefficient—it doesn’t happen every time, or even most times a person is exposed. As Passmore noted, there are conditions, particularly inflammation, that can make a person more susceptible. If one thinks about local HIV exposure as a fire that either goes out—doesn’t result in infection—or spreads then, Passmore said, “Inflammatory signals are fuels that bring HIV-target cells into the genital tract. If you could block inflammation it would be a very effective way of limiting infection.” She identified several inflammatory markers or cytokines in the genital tract of women from the CAPRISA 004 microbicide trialwho acquired HIV. Her talk also touched on the different cytokine profiles found in the blood and concluded with a Venn diagram of inflammation, compartment (blood versus genital tract), inflammation and so on that is worth lingering on for what it suggests about measuring and addressing inflammation as part of HIV prevention. At the end of her talk, Passmore shifted gears from the scientific to the practical and made an important and passionate argument for policy change. “Young women have unacceptably high rates of asymptomatic STIs and bacterial vaginosis”—conditions linked to inflammation. Given the correlation between inflammation and HIV risk, and the high rates of HIV in young women, she called for “an urgent reevaluation of how appropriate our current STI surveillance and testing guidelines are for sub-Saharan Africa.” 

Finally, Omu Anzala (Kenya AIDS Vaccine Initiative) gave a thorough and accessible explanation of the importance of mucosal assays as part of HIV prevention trials—stressing the necessity of gathering information about immune responses in these tissues, as well as the feasibility of doing so in African settings. With a strong focus on Kenyan activity, he described a center of excellence for mucosal work that comprises several collaborating institutions, as well as early work to determine whether nasal sampling could provide relevant information—a potential way to address the cost and invasiveness of genital biopsies and other sampling. He concluded by raising the priority of looking for broadly neutralizing antibodies at mucosal sites—and of designing vaccines to induce such defenses.

Other Presentations We are family?: Babies, mothers, fathers and the ongoing challenges of “PMTCT”
This morning’s session [OA.23] on pregnancy intentions, safe conception and prevention of vertical transmission was, if not the first, then at least one of the early examples of a discussion that embraced both PrEP (pre-exposure prophylaxis) for the HIV-negative partner and traditional ART interventions for prevention of vertical transmission. This, in and of itself, is a thrilling development—since it moves the prevention conversation into a place of shared responsibility and choices for both the HIV-positive and -negative partners in the context of conception. Erika Aaron (Drexler University) [OA23.SY] provided a clear, comprehensive review of “PrEP-ception” decision-making as part of a discussion of the worldwide context of woman-centered PrEP implementation. (Perhaps, as PrEP enters the conversation, we will finally abandon “PMTCT”, which foregrounds the mother’s role in favor of more neutral terminology.) 

PrEP and Option B-plus (ART for life for pregnant and lactating women) are effective strategies, but they only work if they are taken as prescribed. Durban-based researcher Nzwakie Mosery (MatCH) described the role of depression, social support, stigma and structural barriers to care in adherence to ART among 200 HIV-positive women [OA23.02]. Twenty-four percent of women reported depression symptoms; and depression was correlated with adherence challenges, as measured by self report. The information on other barriers spoke volumes about the gaps in effective, accessible HIV and contraceptive services. Sixty percent of the women said that they did not want to be pregnant. One-third of the women attended the clinic on foot, and spent an average of a half an hour to get there—a barrier under any circumstances, but a tremendous consideration as pregnancy progresses. 

These and other presentations in this session complemented the Day 2 (Wednesday) roundtable “Prevention of Mother to Child Transmission Revisited” [RT2], which focused much more intensively on the strategies that could be directed towards the fetus, newborn and infant of an HIV-positive mother to help prevent infection or achieve a functional cure. In remarks from the floor at this session, Susan Allen (Rwanda-Zambia HIV Research Group—Emory University) presaged her talk at this afternoon’s session [RT04.05], which featured  an urgent call for integration of couples counseling into prevention trials and services—nicely summarized by its subtitle, “Most transmissions are in marriage, most pregnancies are not immaculate conceptions, and women aren’t just incubators.” 

Deep thoughts on viral variability
Deep sequencing is a technique that is a strategy for sensitively characterizing rapidly evolving viruses like HIV—including minor, hard-to-detect variants. Two talks at the morning session on viral transmission [OA.21] highlighted some of the subtle but potentially important distinctions in the virus that establishes infection (founder virus). Even if a person is exposed to several different genetic variants of HIV, infection usually involves a single variant. There is a bottleneck—still not understood—created by mucosal defenses that contributes to this phenomenon. Understanding the characteristics of the viruses that establish infection is key for informing vaccines and other strategies that aim to boost immunity in the genital tract. Damien Tully (Ragon Institute) described slight differences in the “genetic footprints” of founder viruses that establish infection in gay men and other men who have sex with men, compared to founder viruses in heterosexual transmission [OA21.05]. Specifically, he identified some site-specific differences in glycosolation—signature sites—that might confer some selective advantage on specific viruses that establish infection at the rectal mucosa. 

Gustavo Kijak [OA21.06LB] used deep sequencing to look closely at the genetics of founder viruses from people acutely infected with HIV in Thailand and South Africa. He focused his talk on four individuals and described how, although it looked like a single variant established infection, close analysis revealed a small population of a minor variant. This is called “cryptic multiple infection.” Soon after infection, the minor variant can very quickly become a larger proportion of the virus found in the blood. 

Understanding these fluctuations and the possibility of cryptic multiple infection is key to a working model of what happens during early infection. 

Building the best possible vaccine: More on selecting adjuvants and immunogens 
This session [OA.25] explored the critical role of adjuvants (immune boosting agents that are formulated as part of a vaccine) and immunogens (the precise elements of HIV selected to present to the immune system). This conference has included many talks related to follow-on work based on RV144, the successful Thai vaccine trial—and this session added to the conversation. Genoveffa Franchini (National Cancer Institute, USA) presented non-human primate data on a study of an RV144-like regimen formulated with the adjuvant used in the original trial in Thailand (alum) or the adjuvant planned for use in the RV144 follow-on trial (MF59) [OA25.01]. A new adjuvant has been selected in hopes of boosting immunogenicity and, therefore, protection in humans. 

Getting real about universal test and treat
Kwame Shanaube (ZAMBART Project, Zambia) presented preliminary lessons from the ongoing PopART trial that is designed to find out whether a “universal test and treat” (UTT) strategy can be delivered with high uptake and acceptability [OA28.03]. Her opening comments were a great reminder of the reasons why models can’t predict, with certainty, what the impact of this or any strategy will be. “They don’t take the complexities of real-life scale up” into account, Shanaube said. PopART is still underway so no data was presented, but Shanaube described the tremendous effort needed to recruit and train health workers to deliver home-based testing, and the discovery that in-home testing may not meet everyone’s needs. She said a “combination of community models” including work-based VCT and more should be explored—a relevant finding for ART programs, not just research projects. 

Is PrEP faster than a speeding tampon?
The discussion of what it will take to achieve real-world impact with existing and emerging strategies continued in the afternoon roundtable “Diffusion of Innovation” [RT3]. Presentations presented timelines and experiences for the introduction of various interventions—from the tampon to female condom to VMMC to PrEP. It can take decades for a product to “catch on”, and success is dependent on smart introduction and investment. The panel made clear that product introduction requires the same (and even more) commitment to strategy, resource and planning that product development receive–and questioned why invest in new product development if funders aren’t willing to commit to future product delivery. 

The work we do together
Eduard Sanders (KEMRI-Wellcome Trust Research Program, Kenya) presented on in-depth work at a coastal Kenyan research site that, over time, addressed community concerns, built trust among gay men and other MSM, as well as site staff skills and comfort in working with this population. Udom Likhitwonnawut (advocate and consultant in Thailand) presented on ongoing, community-led work to ensure implementation of the Good Participatory Practice Guidelines in a country that continues to play a key role in biomedical prevention research [RT4]. 

This is the last full day of the conference. Tomorrow, everything comes together in a final plenary–and then we return to our work in the real world. Stay tuned for a final update and don’t forget to save the date for ourpost-R4P webinar—Thursday, November 6—on the way forward! 

Arm advocates with the appropriate facts so that they can drive change in their own countries

This was originally published on the What’sUpHIV blog that provided live coverage during HIV R4P 2014.

Maureen Milanga, a staffer at Health GAP in Kenya and an alumna of the AVAC Advocacy Fellows program, presented a poster demonstrating how advocates from Kenya, Zimbabwe and Nigeria were able to influence their countries by strategically raising their voices to increase demand for key interventions. Their work has helped secure a number of significant changes—including global WHO guidelines that recommend early ART initiation for sero-discordant couples regardless of CD4 counts. Demand is also driving expanding attention to the need to deliver post exposure prophylaxis (PEP – ARVs given after a person suspects they have been exposed to HIV) for key populations like sex workers in Zimbabwe and South Africa. There has also been increased effective engagement of communities in trials.

However, a lot still needs to be done to scale up pre-exposure prophylaxis, or PrEP (programs that provide ARVs to HIV-negative people to reduce their risk of HIV infection). This includes additional research, demonstration projects and large scale roll out programs.

It is important to note that advocacy requires appropriate strategy for each country in order to create meaningful change. They need to be given basic facts about the research and the prevention/treatment options for them to influence policy makers. Advocates can then frame arguments that help the policy makers see themselves as beneficiaries of the action—whether by saving costs, lives or earning the respect and alliance of the key constituencies driving change.

PrEP for a New Era

This was originally published on the What’sUpHIV blog that provided live coverage during HIV R4P 2014.

It was an exciting morning for pre-exposure prophylaxis (PrEP) using daily oral TDF/FTC (brand-name Truvada). In the morning plenary session, Chris Beyrer, of Johns Hopkins University and president of the International AIDS Society, spoke about HIV prevention in sex workers, gay men and other men who have sex with men. Beyrer pointed out that there is only one country implementing PrEP—the United States—at a national level.

“I can’t wait until the PrEP era begins,” Beyrer said. “Hopefully it is going to be soon.” Beyrer is a staunch human rights advocate—founder and director of the Center for Health and Human Rights at Johns Hopkins—and it is good to hear support for PrEP in the context of a rights-based response. As he noted, there are many concerns in civil society about biomedical interventions like PrEP and ART for treatment and prevention, since the medical establishment is, often, linked with the state—eg governments that may be actively criminalizing and persecuting the very populations who are being targeted with new biomedical strategies. Beyrer’s embrace of both rights and biomedical interventions is exactly what’s needed—and it will be exciting when the PrEP era, as he defines it, begins.

Speaking of the PrEP era, it took a leap forward while the plenaries were taking place, as the French research agency ANRS released a press release announcing that its IPERGAY trial, which had been designed to evaluate intermittent PrEP use, had found evidence of efficacy and was going to end its randomized, placebo-controlled design.

Briefly, this trial was launched after the iPrEx trial of daily oral PrEP showed efficacy in gay men, other men who have sex with men and transgender women. It sought to test intermittent use and had a placebo arm—a design decision that raised ethics questions from the outset, given the evidence of efficacy from iPrEx. The investigators had explained that since PrEP was not available or evaluated in France, the design was warranted. Plenary speaker Brigid Haire, who gave a compelling, nuanced talk on trial ethics and biomedical prevention, mentioned these questions specific to IPERGAY—perhaps at the precise moment that the press release was being released announcing the changes in the trial. (Kudoes to Haire and indeed anyone who isn’t checking email compulsively during conferences…)

In a delicious turn of phrase, Haire referred to the “tantalizing whiff of data” from the UK PROUD study of PrEP in gay men and other MSM. This trial found compelling evidence of efficacy earlier this month—a finding that triggered a review of the IPERGAY protocol. It’s exciting when a field evolves in real time—let’s hope it keeps happening, as fast as Beyrer suggests it should.

HIV R4P Conference Day 2 Snapshot

Welcome to the Daily Snapshot for Day 2 of the HIV R4P prevention conference. As with our Day 1 coverage, this is a selective, whirlwind tour through some of the day’s sessions—all of which are available via webcast 24 hours after they took place. There’s lots more information and insight in the conference’s liveblog and the Twitter feed #HIVR4P. 

Morning Plenaries 
“Epidemiology has been called the basic science of prevention,” said Johns Hopkins researcher and President of the International AIDS Society, Chris Beyrer, at the outset of a comprehensive, eloquent look at the prevention needs for “key populations”, which he defined as populations with disproportionate burden of disease and lack of access to services. Beyrer, who dedicated his talk to health providers caring for Ebola patients, is a passionate advocate of both human rights and biomedical prevention, and his talk is a valuable contribution to the discourse that merges these sometimes siloed arenas. 

Beyrer also said that he “could not wait for the PrEP era to begin.” In fact, the era took a leap forward while the plenaries were taking place, as the French research agency ANRS released a press release announcing that its IPERGAY trial, which had been designed to evaluate intermittent PrEP use, had found evidence of efficacy and was going to end its randomized, placebo-controlled design and offer oral PrEP to all participants. 

Australian advocate, ethicist and researcher Bridget Haire was up next, with a talk that spanned a decade of biomedical prevention research—from the 2004 controversies regarding PrEP trials in Cambodian sex workers—through to the present day, when issues about post-trial access to strategies that show benefit is emerging as a key and sometimes thorny topic. 

Pontiano Kaleebu, leader of the Medical Research Council in Uganda, was the final speaker, providing a really concrete picture of ongoing work in Uganda designed to provide targeted, effective combination prevention—including immediate initiation of ART in sex workers and members of fishing communities. 

Other Presentations
Maturation, parallel paths, strange behavior—HIV and antibodies
B-cell immunity is a major focus of this conference, as noted in yesterday’s blog. Today’s morning antibody presentations continued the exploration of factors in HIV-positive individuals that affect the development of broadly-neutralizing antibodies (BNAbs)— antibodies that block the activity of multiple strains of HIV. In a Monday session [SY01.04], Garnett Kelsoe (Duke University) remarked on how “strange” these HIV-specific BNAbs are relative to other antibodies. One aspect of this strangeness is that the B-cells that produce broadly neutralizing antibodies against HIV have gone through many more rounds of somatic hypermutation than is typically seen in other infections. Somatic hypermutation is the process by which the B cell’s antibody-producing genetic code is progressively revised, potentially leading to an increase in the affinity of the antibody for its target. The steps of this revision are also called a hypermutation “pathway” that leads to mature, BNab-produce B cells. There isn’t one maturation pathway—there are many. And the conference is shedding light on what’s known about what influences these pathways for different BNAbs. Yesterday, Kelsoe gave a fascinating talk on the role of immune “tolerance” in shaping B-cell driven responses to HIV. Tolerance refers to one of the ways the immune system distinguishes self- (safe, not needing an immune response) from non-self (potential threat) substances in the body. Kelsoe explained that BNAb-producing B cells may be eliminated  at tolerance “checkpoints”–and that some of their unusual characteristics may reflect steps taken to overcome these checkpoints. Today, Jinal Bhiman (National Institute for Communicable Diseases, South Africa) [OA12.01] and Elise Landais (IAVI) [OA12.02] described how viral evolution in people with HIV affects the development of BNAbs in these same individuals. An afternoon session [SY06.02] included more exploration of the topic—including a look at “systems serology” which is getting better at predicting antibody efficacy.

RV144 Trial and Follow-on Activities Get a Boost
Several of today’s presentations gave a sense of the what’s happened since the 2009 announcement that the Thai vaccine trial known as RV144 provided modest efficacy in Thai volunteers. Rapid analysis of available samples identified immune factors associated with reduced risk among vaccine recipients including a non-neutralizing antibody. Since the end of the trial, some of the Thai vaccine recipients have been “reboosted”—meaning they received additional immunizations of one or both components of the regimen. Volunteers who received the regimen six years ago were reboosted in hopes of prompting antibodies to develop into BNAbs. (Antibody development and maturation is dependent on a highly-specialized interaction between the virus and the immune system–what parts of the virus are “seen” by the virus affect what antibodies evolve). Michael Anthony Moody (Duke University) presented data showing that this strategy did prompt a development of BNAbs providing insights into how the regimen might be improved (OA12.06 LB). Siriwat Akapirat (AFRIMS) reported on measurable immune responses in rectal secretions of re-boosted volunteers—mucosal immune responses weren’t measured in the original study [OA11.05LB]. Finally, Glenda Gray (Medical Research Council, South Africa) presented on the immunogenicity of the RV144 regimen in South African volunteers in the HVTN 097 trial [OA11.06LB]. Vaccines can have different effects depending on gender, body mass index and background immune activation—so vaccine-induced immune responses can and do vary by geography. The good news, as Gray described, is that the South African volunteers had responses that were as good—if not better—than RV144 volunteers, paving the way for the planned efficacy trials slated to start in 2016. 

Truth, lies and teapots
Anyone interested in adherence, trust-building between trial participants and trial staff, and the ways that participants decide what to disclose, and when, about product use should grab a cup of tea and watch the full session [OA15]. Tea is relevant because it’s the basis of an innovative, simple graphic used to explain the concept of pharmacokinetics (PK) (detection of blood drug levels) to VOICE trial participants in VOICE-D—a protocol that engaged participants after the trial found no evidence of benefit in any of the arms—to understand why that finding might have happened. Participants reported on their product use and then discussed it again, after receiving PK data. The findings are important and intriguing. 

Hormones and HIV
Do hormonal contraceptives, including Depo Provera, affect women’s risk of HIV? And if so, why? The data to date are mixed—some studies say yes, others say no. Today’s session [OA20] added more information to this uncertainty. A South African study suggested a five-fold increase in HIV risk associated with Depo use, perhaps because progestogen increases the number of HIV target cells in the cervix. (So does the natural form of the hormone, progesterone.) But this study wasn’t designed to answer the question directly, and other high-quality studies haven’t found the effect. What’s needed, said conference co-chair Helen Rees, in remarks from the floor, is the planned randomized trial known as ECHO, which would evaluate HIV acquisition in women using three different methods. Rees, who is one of the principal investigators on ECHO, said the trial “appeared” to be close to receiving full funding—a hopeful sign of progress towards certainty. 

Long-acting injectables and other new strategies
In a session [SY07] that provided overviews on a range of next-generation strategies (rings, gels, injectable ARVs), Ian McGowan (MTN) provided some initial data from pharmacokinetic and pharmacodynamics studies of long-acting injectables, including findings of different drug levels in vaginal and rectal tissue and secretions. 

Double-edged swords, competing priorities and a roadmap for communication
Today’s session on the Good Participatory Practice Guidelines for biomedical prevention research [OA19] featured compelling talks on how media engagement with LGBTs can help—or hinder—an effective human rights response; on a Kenyan model for joint priority-setting between LGBT groups and researchers; implementing GPP in the FACTS 001 microbicide trial; and more.  

Penis enthusiasts and other ways to reframe the reality of HIV prevention today
A tweet-friendly session provided both soundbites and deep discussion of what prevention needs to be truly effective. Advocate and leader of the International Rectal Microbicide Advocates, Jim Pickett, said that it was essential to change the discourse. Let’s stop stigma around sex and pleasure, he said. Instead of the term “whores”–which has been used to label gay men and other MSM in the US who choose to use PrEP–he suggested “penis enthusiasts.” 

There’s much more that hasn’t been described in this update—full sessions on prevention of mother-to-child transmission, mucosal immunity and more. We welcome your thoughts and questions—from at the conference or those following from afar. Be in touch! 

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.

First-ever conference devoted solely to HIV prevention R&D taking place in uncertain funding environment

In this post (first appearing on Breakthroughs, a blog from GHTC), Emily Donaldson—program coordinator at AVAC—and Tom Harmon—senior policy analyst at the International AIDS Vaccine Initiative (IAVI)—write about the state of HIV prevention research funding as the first-ever conference devoted solely to HIV prevention research and development (R&D) takes place in Cape Town, South Africa, this week.

Progress toward new tools to prevent HIV infection—including vaccines, microbicides, the use of antiretroviral treatment as HIV prevention, pre-exposure prophylaxis (PrEP) and a host of other options—is being presented and discussed at the inaugural HIV Research for Prevention Conference (HIVR4P) in Cape Town this week.

While much progress has been made over the last few years, a four percent decline in funding between 2012 and 2013 speaks to the uncertain nature of the global environment in which that research is taking place. Such cuts hinder the ability of the researchers in Cape Town and across the globe to continue their work and could delay progress toward efficacy trials and eventual rollout of new prevention options.

Investment data for almost every technology being discussed in Cape Town can be found in HIV Prevention Research & Development Investment in 2013: In a changing global development, economic, and human rights landscape—the most recent annual report by the HIV Vaccines and Microbicides Resource Tracking Working Group.

The data show that the US government continued to fund more than 70 percent of HIV prevention R&D efforts in 2013. The combination of recent funding cuts across all US government budgets and declines in European investment in HIV prevention R&D led to the overall decline in funding from the previous year. Relying on such a small number of very committed donors is problematic when one or more of those donors is forced to reduce their support.The report also highlights funding declines in nearly every category of HIV prevention R&D, underscoring an urgent need to sustain and diversify funding sources through partnerships between governments, philanthropies and the biopharmaceutical industry.

The 2013 data provoke a concern that HIV prevention R&D is increasingly becoming a lower priority for public agencies funding international development, as portfolios and priorities within those agencies shift. Global health and development negotiations such as those around developing successors to the United Nations’ Millennium Development Goals take place far from the context of most HIV prevention clinical trials, but such international commitment at the highest levels can keep HIV/AIDS a priority for development agencies that can bolster support for science, technology and innovation in endemic countries to end the epidemic.

The report also compiles the number of volunteers taking part in HIV prevention R&D trials, which totaled almost 670,000 people in 2013. Most of these individuals are based in sub-Saharan Africa where the epidemic has its most profound impact and where several large-scale treatment-as-prevention and voluntary medical male circumcision trials and projects are underway. However, that balance doesn’t cut across all new prevention technologies—80 percent of volunteers in vaccine and PrEP trials reside in the United States and Europe. Ensuring that new HIV prevention options are appropriate and acceptable means testing them in partnership with those regions and those communities that need them most.

Such communities are represented here at HIVR4P, and we’re excited by the opportunity to see them mingling with the experts working tirelessly to improve the state of HIV prevention R&D science and in turn hasten an end to the AIDS epidemic. However, they can’t do it without a diverse, committed investment base. Funding data show signals of vulnerability in support for HIV prevention R&D and support the need for policymakers and advocates to ensure that the state of the field remains a healthy one.

The HIV Vaccines and Microbicides Resource Tracking Working Group consists of AVAC, IAVI, and the Joint United Nations Programme on HIV/AIDS. The report and summary materials are available at www.hivresourcetracking.org.

HIV R4P Day 1 Snapshot

All this week AVAC is providing daily reports from Cape Town

Greetings from the first official day of the HIV R4P conference. With multiple sessions on a wide range of topics, it’s impossible to provide a complete overview of every day. The good news is that the conference is fully webcast with sessions up on the web 24 hours after they take place—and is also being live-tweeted by many participants, who are providing a sense of quotable quotes, key data and unanswered questions in real time. You can follow that at #HIVR4P.

For those who may want more than 140 characters and fewer than 32 hours of webcast video—the AVAC team and our partners will be providing a daily look at various selected highlights. Here’s a whirlwind tour of Day 1. Please note the webcasts are available 24 hours after they were presented—available here. Additional resources, including copies of selected speakers’ remarks are available at www.avac.org/HIVR4P.

Tuesday Plenary
Helen Rees, Conference Co-Chair and Executive Director of the Wits Reproductive Health and HIV Institute, opened the conference and set the stage very eloquently. She spoke of the synergies across the HIV prevention field that make this conference so exciting, and the reasons why South Africa is an ideal location with such remarkable research capacity, and intense need for additional prevention tools, particularly for women. She spoke about the parallels between Ebola and HIV (stigma, decisions based on politics not science, products not being tested). She also honored Joep Lange and the five other members of the AIDS community who died on the downed plan over Ukraine on the way to AIDS 2014. She reminded us he’d be frustrated we’re going too slowly and would tell us to push the barriers.

Naledi Pandor, South African Minister of Science and Technology, spoke engagingly about the successes in South Africa and what still remains to be done—including a strong pitch for combining behavioral and biomedical prevention into truly effective combination prevention.

Desmond Tutu’s daughter accepted the inaugural Desmond Tutu Award for HIV Prevention Research and Human Rights on behalf of her father.

From there, it was on to the scientific speakers. South African vaccine researcher Lynn Morris (National Institute for Communicable Diseases) walked through the state of B-cell research. This area—focused on the arm of the immune response that includes broadly-neutralizing antibodies against HIV—is covered in several sessions. While the topic is science-heavy, it’s of relevance to advocates and is generating a great deal of excitement. It is, as NIAID head Anthony Fauci described in his remarks, “changing every week.” AVAC will develop an “Antibodies in Plain Language” guide to this science in the coming weeks. Watch this space!

University of Washington researcher Jared Baeten spoke about ARV-based prevention and had five basic messages—plus a terrific picture of his daughter, who turned five today. The messages are below—and the talk is well worth viewing. They are:

  • When ARVs [for treatment or prevention] are taken, they work.
  • You don’t always have to be perfect to be good enough.
  • Barriers are real, and sometimes they are us.
  • PrEP is wanted, but it is not forever, it is not for everyone and it is not one-size-fits-all.
  • There are risks in doing but there are greater risks in not doing enough.

Finally, Dr. Fauci made his remarks by video—unable to attend due to the “epidemic of fear and concern” over Ebola in the United States. He focused on the full array of strategies needed for effective combination prevention.

Also at the Conference:

What we talk about when we talk about anal sex:
Advocates interested in why social science is important—and what “translation” means when it comes to clinical research—should make a beeline for the webcast of Zoe Duby’s (Desmond Tutu HIV Foundation) presentation on the language, terminology and understanding of anal sex in participants in the VOICE trial.
Abstract: OA02.05

Therapeutic vaccines are still a challenge: Harriet Robinson (GEOVAX, Inc) presented data from a therapeutic vaccine intervention in which people with HIV on ART received a DNA-MVA vaccine combination (GEOVAX-B11) and then underwent a treatment interruption. The good news: HIV-specific responses were on hand; the bad news—there was no evidence of control. Watch the presentation to see Dr. Robinson on what’s next for this strategy and cure research.

Abstract: OA05.03

Early ART initiation and HIV-specific immune responses: Early ART limits a person’s exposure to replicating HIV. Effective ART limits viral replication, which limits immune stimulation, which limits the development of HIV-specific immune responses. Alexandra Schuetz (AFRIMS, Henry M. Jackson Foundation) presented on immune responses in people starting treatment early, really really early, and during chronic infection. (The technical terms for “early and really, really early” are scores on something known as a Fiebig stage. Watch the presentation to see what happens.)
Abstract: OA05.04

History affects HIV prevention: Cheryl Louw (Madibeng Centre for Research, South Africa) worked with The Ring Study trial site close to the Marikana platinum mine that was the site of a strike-related massacre in 2012. After the massacre, women began reporting increased aggression from male partners, as well as resistance to the rings (tested in the study) and to trial participation. Louw described the successful steps taken to address the surge in trial discontinuation—but it’s a thought-provoking talk about how real events can put women (and men) at risk, even when they are using a strategy successfully.
Abstract: OA09.02

Tenofovir gel reduces HSV-2 risk: One of the added benefits of oral tenofovir-based PrEP is that it appears to reduce the risk of HSV-2 acquisition and/or ulcer-related adverse events. Today Jeanne Marrazzo (University of Washington) described a similar finding in women who used tenofovir gel in the VOICE trial.
Abstract: OA10.06LB

Treatment is prevention—so is prevention: The treatment as prevention symposium provided an overview of the range of large-scale implementation studies looking at the potential impact of treatment as prevention. It begs the question—asked in the session—of how to deal with delivery of other “primary” prevention options like condoms, VMMC, PrEP and behavior change. Want to find out the answer? Watch the session.
Session: SY03

Broadly neutralizing antibodies are giving up some secrets: The afternoon non-abstract driven session “Overcoming Barriers to Broadly Neutralizing Antibody Induction” featured a series of talks that unpacked the latest increments of progress—and the specific hurdles—in inducing these potent immune responses. Most accessible to advocates with a grounding in immunology, this session—along with Lynn Morris’s plenary, is a great way to get the current state of this field that is evolving as much as the immune responses that it is studying—which is to say, a lot.
Session: SY01

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If It Works, We Should Use It

This was originally published on the What’sUpHIV blog that provided live coverage during HIV R4P 2014.

While numbers and slogans are important in themselves, focus should also be given to interventions that are making positive impact,” that’s how Mitchell Warren, Executive Director of AVAC, opened the 2014 HIV R4P Advocates’ Pre-Conference Workshop.

In his talk, titled, HIV Prevention: Research, reality & context, Warren observed that, “method mix is needed by the community members and not the policy maker.” And so it is critical for civil society to push for access to the full range of biomedical interventions which research has proven efficacious, like PrEP (Pre-exposure prophylaxis) and VMMC (voluntary medical male circumcision). Such interventions have to be embraced by policy makers in Africa, if the quest to end the AIDS epidemic by 2030 is going to be achieved.

Warren summed up by saying that, “It is therefore incumbent upon us to ensure that all our efforts are aimed at rolling out interventions that would save more people from contracting HIV in our communities.” I couldn’t agree more.

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.