On Thursday last week, the HIVR4P conference ended in Madrid. As delegates returned to virtually every corner of the globe, events unfolded that are, by, now, all too familiar: a slew of pipe bombs and a massacre at synagogue in America; an extremist victory in Brazil’s election; continued consternation over the Ugandan president’s public remarks, made earlier in the week, that voluntary medical male circumcision does not reduce HIV risk. Disparate events, but linked nevertheless. Violence exists on a continuum. Slaughter is a shocking extreme; but it is connected to speech, and these days the distance between the two feels far too small. And so, as the conference recedes and real lives demand attention, this final update explores the question: how do we carry on?

Boldly
Kudos to the HIVR4P organizers for including an action at the closing plenary ceremony by young African women as a stand-alone webcast. This is a record of the transformational presence of activists at HIVR4P, as is the essential plenary talk delivered by Maureen Luba on a multipurpose prevention revolution. We carry on by drawing strength from our comrades. There are no finer ones than these.

Inclusively
We cannot afford to be divided, whether we are in a privileged category of race, gender, nationality or sexual identity, or one that is under attack. HIVR4P provided unprecedented levels of research on prevention for transgender individuals. In our previous update, we covered UCLA’s Raphy Landovitz’s research on the “tail” of injectable cabotegravir as PrEP, but neglected to highlight that this analysis from HPTN 077 included six transgender men and one transgender woman in the study. Landovitz rightly highlighted these participants in his talk; understanding how PrEP in all forms works in the context of gender-affirming hormone therapy is essential. We are grateful for the research and for the chance to get it right.

Craig Hendrix (Johns Hopkins University) presented data on the interaction between tenofovir-based oral PrEP and gender-affirming hormone therapy in transgender women; he reported that there was a reduction in the concentration of TDF-FTC in blood and colorectal tissue but that daily oral PrEP would still be protective in transgender women provided it was taken daily. Based on this small study, it appears that all women, whether cis or trans, should use a daily oral PrEP dosing schedule, versus the intermittent or “on-demand” approach that is also protective in cis-gender men having anal sex.

Honestly
There are no easy solutions these days. But often the way through the most difficult moments or problems is via an acknowledgment of human reality: the things we know about ourselves and our communities that we forget when we put on our professional hats, or feel we have to hide some part of ourselves for respect, credibility or safety. This intuition—about what people need and why—is also the source of connection and common purpose. And it may also be the source of combination prevention that works.

“One of the barriers that we have is that we are often delivering our interventions in siloes…from the other life priorities of individuals,” said closing plenary speaker Diane Havlir, who described the SEARCH trial, an innovative study that looked at the impact of a multi-disease health “fair” approach on HIV incidence and virologic suppression in rural East African communities. As Havlir (from the University of California-San Francisco) explained, SEARCH used this approach because of the thesis that HIV needs to be integrated into other priorities, including universal health coverage—an emerging priority for many African governments as well as development funders—as well as individual needs, like sexual and reproductive health, or care for chronic conditions. SEARCH data were also presented at AIDS 2018, so the findings—that incidence dropped in both intervention and control communities—weren’t new. But Havlir’s description of the resistance to the trial from in-country stakeholders was illuminating. She described how people were worried that the trial would flood overwhelmed ART centers with new clients and add costs to struggling health centers and staff. Understanding where resistance arises from—and engaging these concerns at the outset—is part of true stakeholder engagement in research and implementation.

The theme of forthright communication was also in play in Wednesday sessions that focused on the antiretroviral dolutegravir (DTG) and the continued question of whether hormonal contraception, particularly the progestin found in Depo Provera (DMPA) increase women’s risk of HIV. DTG is a potent, well-tolerated antiretroviral that was poised to become standard first-line treatment across sub-Saharan Africa (it has already been adopted in many parts of the world), when a study from Botswana identified the possibility that pregnant women using DTG-containing regimens had a higher risk of fetal abnormalities known as neural tube defects. A review of the data from that cohort to date by Elaine Abrams (ICAP at Columbia University) showed that the finding had not disappeared; that continued follow up was ongoing, with the next analysis scheduled for 31 March 2019. She described how a very small development—a single additional occurrence of NTD in the DTG group—or no additional occurrences in women using DTG group could shift the statistical precision of the estimate of possible DTG-related risk calculated based on the Botswana data.

Sharon Hillier (University of Pittsburgh) delivered a talk, in the same session, about explaining and working with possible risk should, if the world is fair and just, become a viral video for its simplicity, thoroughness and honest grappling with messy uncertainty. She concluded that there was overall a “fair and balanced response” to the DTG finding from the Botswana study, but also excoriated a field that has long neglected pregnancy registries and routine data collection on outcomes among women, including those taking ART while pregnant.

There was more grappling in the session on contraception and HIV, with some familiar dueling data sets: ex-vitro lab-based studies such as the one presented by Janet Hapgood (University of Cape Town) suggest that the progestin in DMPA affects cells and tissues in a way that could increase susceptibility to HIV risk; an observational study in women presented in the same session found no increased risk among DMPA users. The honest answer is: we don’t know if DMPA or any other method increases HIV risk, and we don’t need to know to start offering a wider mix of contraceptive options and HIV prevention tools in integrated programs, and in ART programs for women living with HIV.

Imaginatively
What could prevention options look like in this world? An oral abstract session (OA20 – Into the Future With Delivery Technologies) provided data on tenofovir douche for PrEP—a so-called behaviorally congruent option that could add HIV prevention to something many gay men already use before sex (a douche) (OA20.03 – Tenofovir Douche for PrEP: On-demand, Behaviorally-congruent Douche Rapidly Achieves Colon Tissue Concentration from Ethel Weld, Johns Hopkins University.) A study of 18 men in the US found that a TFV rectal douche is safe, acceptable and tenofovir concentrations above steady-state concentrations associated with efficacy. This same session looked at implants, fast-dissolve tablets and also the use of a 3-D printer for making vaginal rings, ones that might be able to look/feel/dispense various molecules in a faster way than using injectable mold (OA20.05 – Innovative 3D Printed Intravaginal Rings: Reengineering Multipurpose Intravaginal Rings for Prevention of HIV and Unintended Pregnancy from S. Rahima Benhabbour, University of North Carolina). These tools are just the beginning of what we need to imagine, though. We survive by putting one foot in front of the other; we thrive by sustaining hope, and often that comes from imagining a different world: one in which women’s bodies and minds are celebrated, not castigated; one in which everyone can love whomever they choose, health care is a universally-realized human right and no human, anywhere, is illegal.

With Clarity
The final plenary – which began with activism and calls for a comprehensive, integrated and sustained response from both a leading researcher (Diane Havlir) and a leading activist (Maureen Luba) – ended with the NIH Vaccine Research Center’s John Mascola outlining a path forward for HIV vaccines. Rarely has a scientist articulated the complexity of HIV vaccines and broadly neutralizing antibodies with such clarity for a diverse audience. No matter what one’s discipline or prevention option focus, the ability to understand each other’s work and see where it fits into the collective mission of ending the epidemic is essential.

Every member of the AVAC team in Madrid was moved and motivated by the Madrid conference. We know the work is not easy, nor is the world. We will do this together.

Greetings from Madrid! Some meetings are a series of presentations, coffee breaks and cocktails. Others are these things plus something else—a sense of movement towards a consensus, a new commitment. As this HIV R4P conference enters its final day, we feel like it’s safe to say that this conference heralded an energized, nuanced commitment to choice.

In This Update:

• Young women should run the world and if they did, there would be choices and much less shame about bodies and their coverings.
• People really do want different things; use can influence preference.
• Injectables have promise, based on user preferences and trial data, but also real-world challenges, including “the tail.”
• The choice of a vaccine in the future is key—and possible, provided funding remains.
• Choice has many champions—including activist scientists!
• Biomedical tools must live in programs that address structural issues
• We all need to choose our words carefully, and take actions to match

As it happens, AVAC highlighted choice in our annual report, No Prevention No End, released last week ahead of the conference. We noted how politicized the world has become, and how essential it is to reclaim it in speech and more importantly in actions. HIV R4P did this in extraordinary ways. Here are a few takeaways and the sessions that brought this home:

Young women should run the world and if they did, there would be choices and much less shame about bodies and their coverings.
Throughout the conference, the Advocates Corner has been the site of vibrant, spirited engagement, much of it led by young African women attending the conference from Uganda, Tanzania, Malawi, South Africa and many other countries. Over the course of the week, they’ve engaged with researchers, challenged the audience in a powerful opening action, and articulated their needs and desires in creative ways. This included a “panty line”—a powerful, visual uncovering of the hopes, priorities and demands that women are supposed to keep hidden—like our desires. The hotel’s demand that fabric panties be removed from the line, conveyed by the conference staff, prompted strong feelings and swift action. In the closing plenary, these young women took to the stage with signs, panties and pride, to great applause and a strong statement of support from the Conference chairs.

People really do want different things; use can influence preference.
In a Tuesday session called If I Choose, Will I Use, researchers from the Quatro study and from a collaborative between RTI International and the Desmond Tutu HIV Foundation (DTHF) in Cape Town presented results from two different inquiries into what people who may someday use products want in those products. This seemingly logical step is not always taken in the context of HIV prevention—or product development writ large—so products don’t always match people’s preferences. In the next era of choice, if these presentations are any indication, they will. Here are some highlights:

• As Elizabeth Montgomery (RTI International) explained (QA05.04), Quatro was designed to assess the acceptability, preferences, user experience and effect on sexual behavior of four different vaginal microbicide or multi-purpose technology (MPT) delivery forms, using placebo products in roughly 200 18- to 30-year-old African women. All of the women got to use four products: rapidly disintegrating vaginal insert, intravaginal ring (IVR), film and gel. In the first four months of the study, women were asked to use each of the four products in turn either once a week (for the insert, film and gel) or for a month (the ring). They were then asked to choose one preferred product to use as directed for the final month. The study found that preferences varied before and after use and by country—that there was no dominant favorite. Importantly, given the potential regulatory opinion on the dapivirine ring, the ring’s popularity increased the most—it was also the most “polarized” option, insofar as women either really liked it, or did not.

• Quatro tested formulations of real-world products; the DTHF-RTI study (QA05.05) took on preferences at an even earlier stage, involving about 600 young South African men and women in a project that asked them to choose between hypothetical products with a range of qualities, or attributes, including duration of protection, site where the product would be delivered, mode of delivery and pain or discomfort associated with use. As Alexandra Minnis (RTI International) explained, the project was set up in such a way that people could weigh the importance of different qualities in different combinations. Again, there was evidence that people weigh trade-offs: the people in the study prioritized long-acting products with low levels of discomfort associated with use, and favored injections over implants. But every quality or attribute of the product impacted decisions.

• A presentation of qualitative research from the Ring Study (QA05.02) was a reminder of how much can be learned from efficacy trials besides whether a product works or not. Cecilia Mitford (MatCH Research Unit, University of Witwatersrand, South Africa) explained the different factors influencing women’s use of the ring, based on in-depth interviews with trial participants across the study’s six research centers. Factors influencing use included ring efficacy and partner perceptions.

Injectables have promise, based on user preferences and trial data, but also real-world challenges, including “the tail.”

• A leading next generation PrEP product candidate is an injectable formulation of cabotegravir given every eight weeks via an injection in the buttocks. Betsy Tolley (FHI 360) presented data on the acceptability of this approach gleaned from trial participants in HPTN 077—who by and large reported that the injections were acceptable—with embrace of the method increasing from the beginning to the end of the study. That’s the good news…

• …a cautionary note, also from HPTN 077, was delivered by Raphy Landovitz (UCLA Center for AIDS Research and Education) who presented on the duration of drug , after the last injection in the bodies of a subset of 177 people from the trial. By 18 months after final injection, 87 percent of the men (n=60) were below the limit of quantitation (25nanongrams/ml), while 13 percent still had detectable levels of drug in the blood. In women (n=117), 58 percent were undetectable at 18 months; 42 percent of women still had detectable CAB. Sex was an important predictor of the half-life of the product; in this analysis, the half-life of the drug was 45 percent longer in women (all of whom were cis-gender) than men (ditto). BMI was also an independent predictor. The drug that’s left in the body after a final injection is known as “the tail”—and the tail matters because at some point, the drug is still in the body but not at a level that will protect against HIV. When this happens, people are at risk of both HIV and drug resistance. So injectable use will likely require a period of oral PrEP use for anyone who wishes to stop. How long would you need to be on daily oral PrEP to cover the tail? Landovitz calculated that the median time for each sex group to fall below the limit of quantitation—undetectable—for male was 42.7wks (20-134wks) and females, 66.3wks (18-182wks). Trial participants in ongoing efficacy trials of CAB-LA PrEP receive 48 weeks of oral PrEP after discontinuation. These data suggest that this might need to be revisited.

• This same drug is being evaluated, in combination with another ARV, rilpivirine, for antiretroviral treatment. In It Only Hurts a Little Bit satellite session (SA13), Santiago Moreno reported, in moving terms, the transformative impact that injectable ART had on young people who said that, for the weeks between injections, they forgot they were ill, or felt truly healthy for the first time. Around the world, young people are less likely to be virologically suppressed and linked to treatment, so their preferences and experiences are of profound importance. Panelists noted a coming conundrum: injectable ART is only being considered for people who have taken oral ART and achieved virologic suppression for six months, yet the people who may need it the most may not be able to meet these criteria.

The choice of a vaccine in the future is key—and possible, provided funding remains.
While the field awaits results in 2021 or so from the two efficacy vaccine trials in the field, R4P included a number of presentations on experimental vaccine approaches to creating broadly neutralizing antibodies (bNAbs). The goal of this work is to develop products that teach the human immune system to create antibodies like those being given, in pre-made form, to participants in passive immunization studies, such as the AMP trial.

There are three approaches being considered for early human trials from data now mostly in mice:

1. Lineage based vaccine design, or basically retracing the steps a known bNAb has taken to become a bNAb.
2. Germline targeting vaccine design, which finds the scarce “precursor” B-cells that later could become bNAbs and stimulating them to become protective.
3. Immune-focusing vaccine design which focuses all immune responses on one key part of the virus like the fusion peptide at the base of the HIV spike or the V1/2 loop linked to the immune response in RV144. Immune-focusing attempts to get around the problem that the immune system often prefers to create off-target non-protective antibodies. All of these approaches are considering new immunogens like the SOSIP trimer which is designed to look as much like the HIV spike as possible to spur greater immune responses.

On the heels of the Resource Tracking Working Group report presented at the conference declining resources for HIV vaccine research, Robin Shattock (Imperial College London) and his colleagues presented on research from the 5-year €23 million EAVI2020 project. Working with a modest budget in the HIV vaccine world, EAVI2020 plans to design, test and manufacture multiple vaccine candidates, a model perhaps for more financially constrained times.

Finally, so much is going on in vaccine research that Julie McElrath from HVTN noted we “drowning in a sea of data.”” The rise of bioinformatics has highlighted the need coordinate across networks to make data useable. Uniform assays and ultimately common criteria for down selection for clinical trials for efficacy trials are needed to conserve resources and ensure the most promising candidates move forward.

Choice has many champions—including activist scientists!

In Wednesday’s plenary presentation, Raphy Landovitz and Craig Hendrix (Johns Hopkins University) embodied activist principles of naming issues and calling on specific actors to respond to concerns. Hendrix used a toolbox metaphor to take the audience through a “thought experiment” about what they’d like to have in their bedside drawer for a safe sexual life. Did people want the equivalent of a handyperson’s special—drill, hammer, wrench, pliers and so on—or did they just want a hammer, in other words a single option. “Not everything,” Hendrix remarked, “is a nail.” The most important slide was his final one, in which he laid out core tasks for a range of stakeholders with power over the future of HIV prevention research. We find it so relevant and powerful that we have reproduced it here.

Biomedical tools must live in programs that address structural issues
In an oral abstract session (OA10) titled Key to the Response: Populations, Partners and Prevention, researchers reviewed a range of familiar and essential realities: marginalized populations carry a high HIV burden, need biomedical interventions and culturally competent care along with strengthened communities and changes in criminalization laws. Studies from Brazil, Indonesia, Kenya, South Africa, the Ukraine, the US, and Viet Nam all highlighted the degrees of violence by the state, families and societies that impact adolescent girls and young women, sex workers, transgender people, and drug users—as well as the resilience of these groups, and their essential role in designing and delivering solutions that fit into their lives.

We all need to choose our words carefully, and take actions to match
In our first update, we noted that both words and silences matter a great deal at this moment in history—in the world and in our field specifically. In that update, the quote attributed to Dr. Mike Cohen regarding PrEP in women did not include the full text as presented on the slide, which stated, “Concerns about potential limitations of TDF/FTC prevention in women have been noted, and will likely be clarified through ongoing studies (e.g. HPTN 082) and observational data.” We should have used the precise language from the slide, and we apologize for shortening the text as every individual should be heard in the words they choose.

The concerns AVAC has raised, including at length in our AVAC Report 2017: Mixed Messages and How to Untangle Them and at a range of consultations, about the ways that daily oral PrEP is described with respect to relevance for women remain. Daily oral PrEP is less forgiving in women; close to perfect adherence is likely required for protection. This is a limitation faced by many drugs that require diligent use for efficacy. We feel that it is essential that limitations related to PrEP for women be framed as problems to solve via innovative program designs, and that suggestions that a WHO-endorsed strategy may still be require research to validate its use in women can be misconstrued as reasons to delay expanded access. Cohen did not in any way suggest a delay, and we hope the full quotation clarifies this fully. However, AVAC’s advocacy partners have observed countries questioning PrEP’s utility in women and using similar framings to justify their reasoning.

We will cover the closing plenary session in more detail in our final update, and it will soon be available via webcast. It was a remarkable panel of leading researchers and advocates, including the conference co-chairs and Maureen Luba, a Malawi-based member of the AVAC team who works closely with MANET+ and CEDEP. While all the presentations were on different topics, there was a single unifying theme of collaboration, choice and voice. This is a field in which we must find ways to work together and to respectfully disagree. We look forward to working collaboratively and in community with all stakeholders dedicated to scaling up today’s tools and continuing investigation for new ones in the future.

Along with #metoo and many others, #believewomen is one of the social media rallying cries of the past months (and years) as women and allies have taken a stand against violence, assault and the power structures that protect perpetrators, be they an aspiring Supreme Court justice or an employee at the UN agency charged with coordinating the global AIDS response. If silence is violence, #believewomen is the response. At this week’s HIV R4P conference in Madrid, we are hearing both silence and the challenge. In this first of a series of updates from the conference, we bring you a set of session updates, and this overall observation: #believewomen has no borders. It is everywhere. Even when the discourse is polite. Here in Madrid: Skilled, esteemed speakers are saying a lot and… silence speaks volumes.

Many of the silences occur in spaces where the lives and bodies of women, girls, gay and trans people are on the line. A Monday PrEP satellite (SA16 Current State of Play: PrEP Implementation Update and Challenges) focused on experiences delivering oral PrEP in diverse countries and started with an update on implementation progress from WHO’s Michele Rodolph. She emphasized that PrEP works for men and women and that programs should be selective and permissive: targeting the strategy but also offering it to anyone who comes into a clinic asking for the strategy. She also reminded us that the primary areas of scale-up are in the US and Europe, where gay men are the predominant population accessing PrEP.

As John Brooks from the US Centers for Disease Control and Prevention noted in that session, the patterns of access do not mirror the patterns of incidence: black and brown gay men and other men who have sex with men are at the highest risk of HIV and are least likely to access PrEP. Reports from the Jilinde project in Kenya by Daniel Were and the South African National Department of Health by Hasina Subedar—some of the most well-resourced and advanced PrEP programs in sub-Saharan Africa—showed that low uptake and continuation is slowly giving way to incremental increases in use by young women and female sex workers. A presentation by Mike Cohen of the HIV Prevention Trials Network started with the statement that PrEP works in men and women, but then turned to an exploration of data on the ability to offer women a precise estimate of protection associated with daily oral PrEP, and ended with a bullet point stating that “concerns about potential limitations of TDF-FTC prevention in women have been noted, and will likely be clarified through ongoing studies (e.g. HPTN 082) and observational data.

This was a head-spinning destination compared to Rodolph’s curtain-raising talk. The silences in these sessions is deafening. No one remarked on the degree to which racism and white supremacy drive HIV risk in the US. Nor did anyone raise the possibility that it is time, now, for African women—versus American men—to use available data to decide whether PrEP works for them, and to determine whether questions about whether daily oral PrEP work in women help or hinder HIV prevention.

Unfortunately, these silences recurred in the opening ceremony where a spirited yet respectful intervention by advocates called for continued research investment in daily and monthly methods in the category of microbicides—which includes the ARV-containing dapivirine vaginal ring—by the US government and all research funders. Dr. Anthony Fauci, the head of the US National Institute of Allergy and Infectious Diseases, spoke directly after this action and did not address the demands. Instead, he stated that the ring was a non-starter and also did not use the word microbicides, to the great dismay of the African women who had helped lead the action. Dr. Fauci also identified black and brown American men as a clear “demographic hotspot” without addressing structural issues. Silence on racism, silence on women’s desires—happily and profoundly broken by Gcobisa Madlolo, the recipient of the Omololu Falobi Award, who stated that her award was for all women who do not have control over their bodies, and by Linda-Gail Bekker (Desmond Tutu HIV Foundation and President of the International AIDS Society) who, on receipt of the 2018 Desmond Tutu Award for HIV Prevention Research and Human Rights, reminded the audience that the anti-Apartheid archbishop for whom the award was named was clear on the necessity of activism to propel social change. Speak truth to power.

These themes of gaps, questions, unuttered possibilities and implications continued in a robust plenary on Tuesday morning, which included an animated (literally) tour by Tom Hope of Northwestern University regarding early events in HIV infection. This led to some evaluation of so-called topical PrEP (perhaps better known as a microbicide), specifically an intravaginal ring, compared to daily oral PrEP and its ability to reduce risk of HIV. Hope used a single high-dose challenge in non-human primates to evaluate protection provided by the ring and the pill in rhesus macaques. He noted in passing that the high-dose model was sure to raise questions, as it does not mimic actual patterns of exposure. He did not return to this potentially significant limitation as he drew the conclusion that the levels of drug were localized in the vaginal tract, leaving some areas susceptible to infection, at least in the context of the high-dose challenge. Some of the actual human women in the trials of the ring have been protected from HIV—a reality that is worth uttering, and that does not diminish the need to continue to explore markers of protection and early events of infection.

Subsequent Tuesday plenary speakers shed more light on early and local vaginal events. Thumbi Ndung’u’s presentation on the FRESH cohort in South Africa involved insights from a group of young women who visit the clinic twice a week for job skills, educational training and blood draws to identify HIV in its very earliest stages of infection. Over five years of the cohort, incidence has remained very high—at over 8 percent. Women who do acquire HIV based on sensitive tests start ART immediately and some of these women have never seroconverted—meaning infection has not been established in the blood. Ndung’u and colleagues isolated the “founder” virus from these women in early infection and found that single broadly neutralizing antibodies did not block all viral activity of all of these isolates. Right now, the bNAb in efficacy trials (VRC01) is a single monoclonal; combinations are in the pipeline but farther down the road. Based on this, Ndung’u observed that combinations will be what’s needed for efficacy. Unasked questions: what would happen if the site offered PrEP on-site along with its training programs and intensively supported adherence, versus referring out for PrEP? Given that there has been no incidence reduction, yet DREAMS and She Conquers programs (South Africa’s nationally driven version of DREAMS) in the country have shown reductions, albeit, modest, in new diagnoses, is there a standard of care that could be adapted on site to help drop incidence? Given that combo bNAbs are needed and are many years away, can the world really afford not to say the word “microbicide” and act on the ring?

“We are entering the era of the microbiome,” said Sharon Achilles from the University of Pittsburgh, the final plenary speaker, before moving into a deep exploration of the role of vaginal bacteria in HIV risk. Picking up from Ndung’u, she noted FRESH cohort findings that the presence of unhealthy vaginal bacteria associated with bacterial vaginosis was associated with HIV risk. She then looked at how different contraceptive methods impacted presence of these bacteria. Oral and hormonal contraceptives decreased presence of these unhealthy bacteria; the copper IUD increased detectable BV-associated bacteria. This information makes the upcoming results from the ECHO trial, a randomized, controlled trial of the copper IUD, DMPA and the Jadelle implant to directly measure impact on HIV risk, all the more important. Sadly, Dr. Achilles did not mention the trial at all.

Other highlights from the conference included:

Voices in the long-acting PrEP movement
Showing how the voices of possible users of long-acting prevention were and could be listened to during different stages of product design and development was the theme of a session aimed at fostering dialogue between different groups represented at the session. The speakers included people from pharmaceutical companies such as Alex Rinehart from ViiV and Mike Robertson from Merck, researchers such as Elizabeth Montgomery and Leah Johnson from RTI, Maggie Keane from IAVI and Anabel Gomez from AVAC. There was much interest in how to ensure getting feedback from people who may use the products before clinical trials, and a consensus that there is a need for better human-centric research earlier in the development process particularly to identify possible behavioral factors that could affect adherence. Participants identified a key question related to figuring out how to ensure that information about the behavior and preferences of users of today’s products is gathered in a way that is relevant to future products.

GPP a must in clinical trials: Nelson Michael
“Community engagement is not just “nice to have”; it’s essential to clinical research,” Rt Col. Dr. Nelson Michael of the US Military HIV Research Program (MHRP) said. He addressed a group of GPP implementers, advocates and other research team staff at a GPP focused session on Monday, October 22. Michael shared how lessons learned during the RV144 vaccine trial in Thailand are informing MHRP’s work in Germany today.

Cate Hankins of the Amsterdam Institute for Global Health & Development (AIGHD) and AVAC’s Stacey Hannah facilitated the satellite, which delved into 10 years of implementation of Good Participatory Practice (GPP) in biomedical research, with interactive discussion around successes, challenges, and strategic directions for the future. The meeting explored consensus on GPP as a standard in clinical trials, and its measurement. Participants received tutorials of new innovative GPP tools, such as the Engage! online platform for the GPP Community of Practice and the new Engagement in Ethics Review online course.

“If you don’t work with the community, you’ll fail,” said Michael, who served on the Obama Presidential Commission for the Study of Bioethical Issues.

What’s next for bNAbs for prevention?
A pre-conference session reviewed where we are in the next stage bNabs for prevention beyond the VRC01 antibody currently being tested in AMP. There is increasing emphasis on the likely need for more than one antibody for any prevention formulation (possibly 3 or more) to avoid existing or developed resistance seen in bNAb for treatment. bNAb combos might need to be matched regionally to provide better breadth (e.g. a clade C passive immunization), The durability of antibodies for prevention is being explored. Gene modifications of the LS region could extend half-life four times as long from the current two months but might take slightly longer to reach effectiveness after infusion.

The AMP trial testing VRC01 in two trials in Africa and the Americas is fully enrolled as of October 7 with no serious adverse events after 30,000 infusions. Larry Corey suggests that VRC01 is possibly the safest bNAbs treatment ever.

At a satellite session on HIV Prevention for Pregnant and Breastfeeding Women, Renee Heffron summarized data that pregnant women are 2- to 3-fold more at risk then women who are not pregnant, with the risk rising 4-fold in post-partum women. Yet the dearth of research and hence data on the safety of drugs for pregnant women often mean that their safety is only captured in post-marketing evaluations and off-label use. There’s a palpable tension between providing access to PrEP to pregnant women now due to the urgent need vs. ensuring there is enough safety data before use. Dr. Abednego Musau described Jhpiego’s experience in providing PrEP to pregnant and breastfeeding women in Kenya while Dr. Bonus Makanani described planned MTN trials to study PrEP and dapivirine ring use in 4 cohorts of pregnant women (MTN 042) and in breastfeeding women (MTN 043). Research in this community has traditionally had a protectionist attitude but this is changing with more and more ethicists challenging that we need to move from assumed exclusion to presumed inclusion, of women in clinical trials. Advocates are urging that US regulations be revisited so that pregnant women are able to reap the same benefits from research as other populations and have a right to safe, efficacious, appropriately dosed therapies that have been studied specifically in pregnant and breastfeeding women. All women—in all stages of their reproductive and sexual life—have the right to use safe and efficacious drugs that have been studied specifically for them.

If you want to view the sessions, visit the HIV R4P webcast portal to stream these and any other conference session. And for real-time coverage, follow the conference hashtag, #HIVR4P2018.

Stay tuned for additional updates as the week unfolds!

Last week, we talked about some sessions we are looking forward to at next week’s HIV Research for Prevention 2018 conference in Madrid. We also included information on how to follow your favorite prevention issue, whether in-person or from afar. This week, we’re sharing more details on programming and spaces for advocates!

Find continuing support for your advocacy and expand your knowledge of critical issues at the Advocates’ Corner (AC), found by the Estrasbrugo Room. The AC will be open throughout the conference, and in addition to the materials displays and opportunities for informal networking and fun games, the Advocates’ Corner will play host to a program of activities scheduled during breaks in the conference program. Don’t forget to pick up a hard copy of the new AVAC Report—No Prevention, No End—hot off the press!

You can download the full Advocates’ Corner program here—and please join us on Monday afternoon at 15:00 for a welcome reception!

To help plan the rest of your time in Madrid, download this roadmap of conference sessions and satellites, which is sortable by intervention.

And, as always, look for real-time updates from AVAC’s Twitter feed and updates from the Advocates’ Network for the latest on the research and the complex work of implementing the tools that exist today.

The entire program for R4P is available here. If you are tuning in remotely, there are webcasts from current and past conferences.

Here’s to the work ahead in Madrid and afterward!

“Science, theory and practice of engaged research: Good Participatory Practice and beyond,” a special supplement of the Journal of the International AIDS Society was published in October 2018. This issue tracks practices and articulates the value of GPP and stakeholder engagement in clinical trials across fields, research areas, geographies and populations.

This supplement was supported by AVAC with funding from the Bill and Melinda Gates Foundation and via the Coalition to Accelerate and Support Prevention Research (CASPR) through the US President’s Emergency Plan for AIDS Relief (PEPFAR) and the US Agency for International Development (USAID).

At AVAC we are looking ahead with anticipation to the biennial HIV Research for Prevention 2018 conference to be held in Madrid, October 21-25. Affectionately known as R4P, it’s a space where HIV prevention takes center stage. Whether you’re headed to Madrid in a couple weeks or following the action from afar, AVAC will keep you connected! Read on for information on AVAC sessions, a sortable roadmap, the Advocates’ Corner (open all week) and more!

For those joining in-person, use this roadmap of conference sessions and satellites, sortable by intervention, to find what interests you at the conference.

From updates on major trials to the complex work of implementing the tools that exist today and all the advocacy needed to get it all done, our dispatches to the Advocates’ Network keep you informed. For real-time coverage follow AVAC’s discussions on Twitter.

If you plan to be in Madrid, you won’t want to miss the satellite sessions AVAC has organized with partners (more below) including a Sunday-morning pre-conference for advocates. Register by Octoberober 17th and get an in-depth and of-the-moment view of the field and advocacy priorities to carry with you throughout the conference.

Find continuing support for your advocacy and expand your knowledge of critical issues at the Advocates’ Corner (AC), found by the Estrasbrugo Room. The AC will be open throughout the conference, and in addition to the materials displays and opportunities for informal networking, the Advocates’ Corner will play host to a program of activities scheduled during breaks in the conference program. Stay tuned for the final AC program, available next week!

The entire program for R4P is available here. If you are tuning in remotely, there are webcasts from current and past conferences.

Here’s a calendar of satellites and sessions of interest:

Sunday, 21 October

Advocates’ Pre-Conference Workshop
AVAC, IRMA, NHVMAS
Provides an overview of the field and explores cross-cutting issues, priorities and common goals. Register here.
Location: Dresden & Stuttgart

Planning for Success: Next Steps for Dapivirine Ring
OPTIONS, IPM
Stakeholders share research and experience to inform next steps for introduction.
Location: Burdeos

Social Sciences in Vaccine Trials: A Booster to Recruit Volunteers
ANRS, Vaccine Research Institute
Time: 12:30-14:30​
Location: Marsella

Monday, 22 October

Current State of Play: PrEP Implementation Update and Challenges
AVAC, WHO
A look at the status of PrEP and future products, and approaches to implementation in low and middle income countries, including challenges and controversies.
Time: 8:30-11:30
Location: Bristol

Voices in the Long-acting PrEP Movement: Fostering Dialog Between End-users and Product Developers During the Product Development Process

AVAC, RTI International, Desmond Tutu HIV Research Foundation, IAVI
Time: 8:30-11:30
Location: Burdeos

GPP@10—Setting New Standards for Clinical Trial Engagement Globally
AVAC, Amsterdam Institute for Global Health and Infectious Diseases
How Good Participatory Practice evolved over the last ten years with a look at implementation, challenges, and the status of GPP as a standard in clinical trials.
Time: 8:30-11:30
Location: Marsella

Whose Desire? Whose Choice? A Debate on the Future of HIV Prevention
AVAC, IRMA
Panelists unpack the priorities for HIV prevention research and product development and debate what it means to give people choices.
Time: 12:00-15:00
Location: Oxford

Accelerating a Labor of Love: Time to Transform HIV Prevention for Pregnant and Breastfeeding Women
AVAC, Jhpiego, MTN, PHASES
A look at the growing body of evidence and advocacy for biomedical HIV prevention options for pregnant and breastfeeding women.
Time: 12:00-15:00
Location: Estrasburgo

The Omololu Falobi Award for Excellence in HIV Prevention Research Community Advocacy
African Microbicides Advocacy Group (AMAG), AVAC, IRMA, Journalists Against AIDS in Nigeria (JAAIDS), NHVMAS
This award honors individuals who have shown extraordinary leadership and commitment to HIV prevention research advocacy and inspired others to action. This year’s recipient will be announced during the opening session, 17:47-17:55.
Location: Auditorium

Tuesday, 23 October

Entry Into the PrEP Continuum (oral abstract)
Tracking Global Oral PrEP Provision: The Who, What, Where of Oral PrEP
Time: 10:30-12:00
Location: Marsella, Burdeos & Estrasburgo

ARVs for Prevention: Extrapolating from Data to Clinical Practice (symposium)
The PrEP Paradigm for Prevention, Advocacy and Implementation in sub-Saharan Africa: Strong Starts, Short Cuts, and the Use (and Abuse?) of Data
Time: 15:00-16:30
Location: Marsella, Burdeos & Estrasburgo

Wednesday, 24 October

Accelerating Product Introduction for Impact (roundtable)
Time: 15:00-16:30
Location: Bristol

Trials and Tribulations in Roll Out (poster discussion session)
Time: 16:45-17:30
Location: Oxford

Thursday, 25 October

Opinion 360: Meaningful Engagement From Research to Roll Out (oral abstract)
Time: 8:30-10:00
Location: Oxford

Putting It Together: Strategies to End the Epidemic (closing plenary)
Implementing a Multi-disciplinary Prevention Revolution
Time: 15:00-16:30
Location: Auditorium

Here’s to the work ahead in Madrid and afterward!