AVAC at HIVR4P 2018, Update 3: How we carry on

October 29, 2018

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?

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.

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.

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.

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.