HIV R4P – HIV Research for Prevention

October 28, 2014

Dear Advocates,

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 isfully 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:

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 ASPIRE 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

Best,
AVAC

HIV R4P Day 2 Snapshot

October 29, 2014

Dear Advocates,

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-producing 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 inVOICE-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!

Best,
AVAC

HIV R4P Day 3 Snapshot

October 30, 2014

Dear Advocates,

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 liveblogand 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!

Best,
AVAC

HIV R4P Day 4 Snapshot

October 31, 2014

Dear Advocates,

Greetings from the fourth and final day of the HIV R4P conference in Cape Town. As with the previous days’ summaries—all of which can be found atwww.avac.org/hivr4p—this is a selective, whirlwind tour through some of the highlights of a meeting that reflected tremendous momentum, energy and excitement across the HIV prevention research spectrum. Webcasts of all the sessions are available 24 hours after they take place. The live blog,What’sUpHIV, has nearly 50 posts from advocates, African journalists and researchers. It is definitely worth taking a look. And Twitter, at #HIVR4P, has great images of many sessions describe below—and much more.

Although the conference ended today, the work together is just beginning. We hope you’ll register nowfor a webinar next Thursday, November 6, that will look at key themes and action items emerging from this meeting.

Morning Sessions
No such thing as a failed trial
This, for many years, has been a mantra in the biomedical prevention field. If the trial recruited and retained participants, and got a clear answer about a product—then it could in no way be called a failure. But what about when participants don’t use the product often enough to get a clear answer—what do you call that trial? One of the themes throughout the week has been how much the prevention research field has learned from VOICE—which had low rates of adherence across oral and gel tenofovir prevention arms. It was not the outcome anyone would have wished for. But the wealth of insight into the gaps in communication, context and motivation that can exist between women and research is incredibly rich—and might not have emerged, had VOICE not provided a “wake-up call” to look closely at difficult issues.

Two talks in the session Challenges of Biomedical HIV Prevention Trials [SY10], reflected on lessons learned from trials that didn’t go as hoped or planned. Jeanne Marrazzo (University of Washington) [SY10.01] reviewed many of the challenges—“life is messy,” she said—and showed a really useful slide summarizing the ways that the VOICE result had changed the model for future trials. She ended her talk with a quote from Winston Churchill, “Success is not final. Failure is not fatal. It is the courage to continue that counts.”

“The trial becomes the protagonist in a story about its life,” said Jonathan Stadler (Wits Reproductive Health & HIV Institute, South Africa) [SY10.04] in a presentation that delved into the ways that myths and rumors about the trial and its experimental products can circulate in waiting rooms and outside the clinic, impacting on womens’ decisions to use the products while in the trial.

Meeting women’s many needs
A session on multi-purpose prevention technologies [RT05] provided a glimpse of the future, as multiple presenters discussed the pipeline, regulatory considerations and potential study designs forcombination prevention tools that would provide contraception as well as protection against HIV and/or other STIs.

Beyond basic science—antibodies enter the clinic
Differential use of Antibodies in Prevention [SY12] continued the discussion of the possible ways that broadly neutralizing antibodies could be harnessed and induced as HIV prevention tools—another key theme of the conference. Barney Graham (NIH Vaccine Research Center) [SY11.01] provided an update on clinical development of VRC01, a broadly neutralizing antibody developed by the VRC, describing two ongoing studies to establish the safety of this product. One is taking place in people with HIV, the other is enrolling HIV-negative individuals. He reviewed the slate of future trials planned to explore different doses, routes and schedules—a sequence that could eventually lead to efficacy evaluations of VRC01 as a prevention tool for HIV-negative infants and high-risk adults. Even as VRC01 moves through clinical trials, there are efforts underway to engineer the BNAb to be even more potent. Neal Padte (Aaron Diamond AIDS Research Center) [SY12.02] described work, in collaboration with David Ho, also designed to engineer potent BNAbs—including clinical trials with one candidate and several more that are in preclinical development, with the goal of selecting one to bring into human evaluations. While all of these concepts are still in their early phases, the session—and the conference as whole—gave a sense of the concrete, if incremental, steps that are moving this critical field forward.

Closing Plenary Session
Getting it right
Douglas Shaffer (US Office of the US Global AIDS Coordinator) continued the theme of safeguarding human rights as part of an effective HIV response in a talk that also highlighted the evidence—from models—that combination prevention incorporating ART, VMMC, condoms, PrEP and other strategies is key to achieving an end to the AIDS epidemic. Continuing with a “status quo” response won’t achieve these results. To frame its work and change the paradigm, the US PEPFAR program has adopted a “Right Things, Right Places, Right Time” approach to guide spending and program design, which he presented in a slide at the end of his talk.

P-Values
A p-value is a statistical term used to indicate the probability that a research result is a coincidence, rather than an actual finding. There was plenty of actual truth—and an alliterative festival with the letter “P”—in the talk by Alex Coutinho (Founding Director of the Infectious Disease Institute, Uganda) about what’s needed to scale up HIV prevention science from the laboratory to the village. In the move from policy to practice, Coutinho highlighted the need for “Partnerships; planning and processes; pesa, pula, pound and pennies; push and pull approaches; providers’ perspectives; population preferences; and pressure from activities.” (This was just the one of the “P”-value laden slides…watch the webcast for more.) “We are far more credible when we combine science with activism,” he said—a refrain that has been echoing through this conference, and that will be exciting to reevaluate at HIV R4P 2016. (Wondering where it will be? Read on!)

Walk the walk
Glenda Gray (Perinatal HIV Research Unit, South Africa) used her talk on antiretrovirals for prevention to highlight the compelling science supporting their efficacy and the considerable challenges to translating that efficacy into clinical benefit. She said that much of the billions of dollars spent on research has been wasted due to failures in dissemination. “All breakthrough and no follow-through,” in a succinct formulation that she borrowed from a colleague. This isn’t for lack of cost-effectiveness, either. PrEP, Gray showed, can be cost effective when targeted to the highest risk populations. Lest this seem improbable, consider that the early results from demonstration projects show that individuals at highest risk are selecting PrEP and using it consistently—suggesting that, when provided with the right information and unbiased access, will make the choices that are best for them. The issue of bias and stigma is another huge issue in health care settings—and a major obstacle. Gray made a strong case for how the health and legal systems have failed sex workers, citing astronomical rates of abuse, violence and discrimination reported at the hands of both the police and health providers. She cited a systematic review showing that decriminalization of sex work could avert roughly 30-45 percent of new HIV infections worldwide over the next ten years. Biomedical prevention doesn’t often engage with legislative issues—but, combining Shaffer’s, Gray’s and Coutinho’s messages, it’s clear that this community needs to find and harness its activist energy and challenge the laws that undermine public health.

Honoring heroes lost too soon
Manju Chatani-Gada (AVAC) presented the Omololu Falobi Award, a biennial honor given in memory of a tireless activist, organizer and journalist who, “lived life in a hurry as a young visionary leader.” Falobi co-founded NHVMAS, the Nigerian HIV Vaccine Microbicide Advocacy Society, as well as helping to lead the Nigerian group Journalists Against AIDS, before his untimely death in 2006. Chatani-Gada explained that this year the award recipient was another Nigerian activist and hero who shared many similarities with Falobi, including a tragic, untimely death earlier this year. Oyelakin Taiwo Oladayo, known as “Taiwo”, was killed in a car accident just six days after his wedding. His life was remarkable for its bravery, commitment and action. Chatani-Gada said, “Taiwo was a passionate advocate for the rights of young people living with and affected by HIV and AIDS with a special focus on the rights and dignity of those who are most marginalized. He was a true son of Africa—championing other African advocates and developing a mentorship program to nurture others. While he focused his efforts in Nigeria, he was also part of the global community of activists who aspired to end the epidemic. As a young person living with HIV himself, he never let that—or anything—get in his way. He had many dreams and many aspirations for the future, as an international activist, as a photo documentarian, as a politician…. Like Omololu, he lived his life in a hurry. And like him, he left his mark on all those who met him.”

Deliver, Demonstrate, Develop—Tools to end the epidemic 
The Honourable Minister of Health for South Africa, Aaron Motsoaledi, received a warm welcome from conference co-chair Helen Rees, and provided a galvanizing vote of confidence in the role of HIV prevention research in ending the epidemic. He highlighted South Africa’s role in HIV prevention research, including its ongoing leadership in trials of microbicide gels and rings and vaccines that build on the positive results of the RV144 trial. He also looked beyond the continent, hailing the results of the PROUD and IPERGAY trials of PrEP in MSM—both trials stopped early after overwhelming evidence of benefit—and said that South Africa needed to expand PrEP access, particularly in female sex workers, young women and MSM. He also highlighted the need to address human rights issues as part of an effective AIDS response—a key theme for the meeting, and a great issue for a South African leader to raise from the podium. Amandla!

Optimism and obstacles
Conference co-chair Robin Shattock (Imperial College, London) gave closing remarks, on behalf of his colleagues, that summed up the key themes and great sense of shared purpose at the meeting. Shattock spoke of the optimism that the meeting had generated. “Why optimistic? Because the science is outstanding and this is a key moment of change in the field.” He spoke of the “new and achievable” goals across interventions—from broadly neutralizing antibodies to microbicides to PrEP—and of the exciting engagement of new young researchers, the “lifeblood” of the field. But, he noted, it is both the best and the worst of times, as research funding is falling (see the most recent trends from a report from the HIV Vaccines and Microbicides Resource Tracking Working Group) at the moment when significant change is possible, and breakthroughs within reach.

From the “Mother City” to the “Windy City” 
HIV R4P 2016 will be held in Chicago, US—which is nicknamed the Windy City, just as Cape Town is known as the Mother City. Nelly Mugo (University of Nairobi) accepted the hand-over as one of the four conference co-chairs for that meeting—which will take place in a country with hot-spot epidemics among MSM that are equivalent, in incidence and prevalence, to the most severe in sub-Saharan Africa. The other co-chairs for the 2016 meeting are Thomas Hope (Northwestern University, US), Lynn Morris (National Institute for Communicable Diseases, South Africa) and Jeanne Marrazzo (University of Washington).

All of us on the AVAC team want to thank you! It’s been energizing and exciting to work with so many partners in Cape Town, and to hear from so many more who’ve followed R4P from abroad. We will see you in Chicago in 2016 and many times before, we hope, as we continue to plan, prioritize and act for effective change. Don’t forget to register for the post-R4P webinar to continue this work.

Best,
AVAC