February 1, 2021
There are a number of excellent sources of news on the conference including coverage from aidsmap, Bhekisisa and this roundup from AVAC. Last week, we also highlighted findings from the AMP study of passive immunization with an antibody known as VRC01, which did not show overall protection in two studies, but did prevent infection by HIV that was highly-sensitive to the antibody. AVAC is finalizing an Advocates’ Guide to the AMP Results and hosted a lively discussion of the findings in the Advocates’ Corner—a vibrant virtual space that’s open throughout the conference.
HIV isn’t the only field looking at antibodies for treatment and prevention. On Tuesday, a one-day conference on COVID-19 prevention will look at the science and politics of developing new vaccines and therapeutics, and the work to be done to close the yawning gap in access to approved COVID-19 vaccines. You can follow along on social media #COVIDconf and look for AVAC to recap highlights in our week 2 R4P round-up next week.
Below is a longer take on some of the key themes from the first week.
Making Do With “Good Enough”: The first week of HIVR4P
by Emily Bass
The first week of the HIV Research for Prevention (HIVR4P) Conference wrapped up with a surprising and welcome sense of intimacy and embeddedness in the real world. Presenters spoke from their homes and offices, with bookshelves, art, the occasional guitar. Instead of speaking from podiums in windowless conference rooms with dimmed lights, speakers spoke from wherever they were—with the light slanting often evoking a time zone far away from where another viewer was sitting. Moments of silence for those lost to COVID-19 often started and ended with the session chair breathing deep. During a moving tribute to Gita Ramjee, lost to COVID-19 in the earliest days of the epidemic, I was alone in my apartment, and also together with the whole conference grieving. We were not together but we did the best we could.
In many ways, the experience of being “at” the conference held the core lessons for the field from the presentations: Meet people where they are; do not make the perfect the enemy of the good; listen to each other, even when it’s hard.
Meet people where they are
A range of evidence from studies of oral PrEP programs underscored the importance of creating programs that meet people’s needs. Kenya’s national PrEP program was, initially, “convenient to the system, not to the user,” said Daniel Were of Jhpiego, a partner in the Kenyan Jilinde program for PrEP rollout. “Simplifying, demedicalizing and decentralizing,” PrEP in Thailand, including shifting delivery into key population-led service sites helped the Thai PrEP program achieve a 300 percent increase in uptake among transgender people, reported Nittaya Phanuphakat the same session. In South Africa, a study of oral PrEP among pregnant women—which also found higher initiation and continuation among these women compared to women who were not pregnant—noticed a major dropoff in refills after COVID-19. The research team got on the phone and asked women what they needed, and acted on what they heard. To alleviate fears of acquiring COVID-19 in long clinic queues, the program offered PrEP pickup at clinic gates. Women just had to text and someone brought the meds they needed. The SEARCH study, which documented incidence declines after PrEP introduction, offered refills on beaches, at home and in informal, non-clinic based settings. “Any slight inconvenience and most [people who use PrEP] are likely to drop along the way,” Were said. “I might go this month and not go next month, because my finances might not be able to carry me,” said Josephine Aseme, a Nigerian health activist and current AVAC Fellow who also uses PrEP.
Implementers of and advocates for oral PrEP programs leaned into the work of designing programs that help people start PrEP not just once but several times. Data from a range of studies show that people start, stop and restart oral PrEP; in SEARCH and Jilinde, this cycling was lower among people who remained at high risk of HIV. Cycling on and off an antiretroviral for prevention runs counter to the antiretroviral treatment model, in which people who start ART are generally asked to remain on treatment for life. But, as AVAC Report discussed in 2019, measuring performance against PrEP initiation and retention may not give a clear sense of PrEP impact in the community. Better measures of “effective use” wouldn’t just look at whether someone stopped or started but at how that pattern related to their own risk; measures of impact might look at coverage within a community as measured by refills or volume of drug dispensed over a certain period of time. Nittaya Phanuphak said that Thai policy makers were asking “traditional questions” about retention. In response, the Thai PrEP implementers are working to familiarize their government counterparts with the notion of “effective use.”
Do not make perfect the enemy of the good
The dichotomy between “traditional” measures of retention and newer approaches to measuring effective use of oral PrEP played out in the conference itself; in some sessions, low retention rates in oral PrEP program were called “sobering” or used to make the case for emerging prevention strategies like the Dapivirine Vaginal Ring (DVR), which was recommended by the World Health Organization as part of combination HIV prevention the day before the conference began, or long-acting injectable cabotegravir (CAB-LA).
CAB-LA made waves at the meeting, with new and expanded data from the HPTN 084 trial in cisgender women. In late 2019, the trial announced initial efficacy findings following an interim DSMB review; the data have not yet been published, but data presented by Sinead Delaney-Moretlwe showed that incidence was low in women randomized to receive both oral and injectable PrEP. In women assigned to the daily pill, incidence was less than 2 percent; in those assigned to receive the injectable it was less than one percent. By comparison, incidence in other HIV prevention trials in similar populations over the past 15 years have consistently been closer to 4 percent. Both options were safe and reduced risk. The injectable was comparatively more effective—reducing risk by 89 percent more compared to women taking oral PrEP. There were equivalent rates of adverse events reported in both trial arms, and data from women who became pregnant during the course of the trial showed no safety issues related to product use. Participants who became pregnant were offered open-label TDF/FTC but all injections were discontinued. HPTN 084 has little data on the so-called “tail”, the period in which cabotegravir is still in the blood but not at levels that would prevent infection. A person who stopped injections but remained at risk of HIV would need to use another prevention option to reduce risk, but little is known about how long people would need to be concerned about the tail. Delaney-Moretlwe said that there isn’t sufficient data from 084—where very few participants discontinued the injection—and that this information could come from open-label extension trials.
The conference also brought data, presented by Sharon Hillier, from a Phase IIa trial of a monthly PrEP pill called Islatravir. The data are from 192 participants and found that the monthly dose was safe and well tolerated, and that it led to blood levels well above the protective threshold that the investigators had calculated based on animal data and studies of Islatravir as a therapeutic treatment in people living with HIV.
In discussions of the monthly pill and the bimonthly injection, speakers celebrated the coming moment when PrEP-focused programs will have a range of options—from a vaginal ring, to a daily or monthly pill, to an injection. Such programs would have much in common with the ideal contraceptive service, which offers people a range of options. At times, the conversation seemed to veer away from the reality of these contraceptive programs—which, in many countries in East and Southern Africa, offer a limited number of choices or, since COVID-19, no options at all during periods of stockout, service disruption or lockdown. Several speakers said that women in sub-Saharan Africa “like” or “prefer” injectable hormonal contraceptives, and while this is true for some women, it is also true that many women receive the injectable because it is what’s offered to them—or because it is the only long-acting discrete method on the shelf.
This week at R4P, Jacque Wambui, an HIV prevention and women’s health activist from Kenya, will present civil society work focused on precisely this issue in an abstract on civil society advocacy related to the ECHO trial. Moving forward, it’s going to be essential for prevention advocates of all affiliations—researchers, activists, potential users of products, policy makers and funders—to look at the reality of “choice” in the context of constrained options, and ensure that biomedically-focused PrEP programs offer options preferred by people, not just the health system.
Listen to each other—even when it’s hard
A reminder of the reason why oral PrEP is critical right now—and for the foreseeable future—came from Gcobisa Madlolo, a South African feminist activist who talked frankly about taking oral PrEP to be “rape ready”, her own experiences with sexual violence and the ways that she and her friends support each other in strategies, including PrEP use, that provide resilience and safety in the face of daily threats to women’s bodily autonomy. Conversations about people discontinuing injectables, or other methods, because they’re no longer “at risk” are important—so is understanding that in every place, there are some people who cannot choose if, when and how they are at risk of HIV, sexual and other forms of violence. The number of people who do not have that fundamental choice has risen since the onset of COVID-19 and is the devastating new context in which HIV prevention must function.
More tough, necessary conversations will occur in the context of the new UNAIDS Ethical considerations in HIV prevention trials guidance—a major update to a document that has long served as an essential framework for trial design and conduct. This is the first update in 13 years. When the last version was published in combination with the Good Participatory Practice guidelines, the field was grappling with whether participants in prevention trials should be offered the best proven standard of prevention, even if a given strategy such as voluntary medical male circumcision or oral PrEP was not available in the country or community. The alternative view held that trials needed to offer the best available standard—tying prevention to national public health programming. Guidance Point 11 of the new ethical considerations states that participants should be offered the WHO-recommended package of interventions at every stage of the trial—including pre-enrollment—and to cohort participants. This is a major shift with immediate implications for trials like the upcoming Phase III study of Islatravir—with WHO recommendation of the Dapivirine Vaginal Ring, the decision not to offer it requires, per the guidance, consultation and discussion. That’s just one example of a complex issue that the new guidance will help to shape conversations on. In the coming months, AVAC and partners, working with trial teams on a range of research projects, will ensure that ongoing conversations and decisions reflect the new reality.
More substantive dialogue is coming this week and I, for one, can’t wait. This year’s conference, it’s real-time questions and comments during official sessions and virtual “hallway” discussions in the Advocates’ Corner, is a reminder of how HIV activists and advocates of all stripes have always found ways to be connected, build community and share strength, even in the hardest of times.
See you in the virtual hallways this week!