New Resources on!

Read on for a roundup of new resources on and!

It’s one year into the COVID-19 pandemic, and the pace of advocacy for many people has only accelerated. In this time, when vast quantities of information—good and bad—must be sorted and priorities set, AVAC has been generating resources to help you keep up-to-date and to inform your advocacy.

HIVR4P in 3D

Okay, maybe it’s not really three dimensions; it’s more! Catch up on many angles of R4P starting with AVAC’s coverage:

Recordings from the Advocates’ Corner went deep into the content and include insightful, lively exchanges:

Funding for HIV Prevention R&D

The 16th annual analysis of funding trends in HIV Prevention R&D is out with 2019 data, and it can all be found on a newly launched website: The annual report is a collaboration among AVAC, IAVI and UNAIDS, and the website includes 20 years of funding trends.

1 Million PrEP Initiations…almost

These two resources will help you understand the trends in PrEP uptake, and keep you up-to-date on PrEP initiations around the world, which is fast approaching 1 million but still well below global targets.

Ending TB

AVAC, Partners in Health, Friends of the Global Fight, Results, Treatment Action Group (TAG) and the Zero TB Initiative collaborated on a report and a new website that includes case studies from around the world. Find out what successful programs in Cambodia, Ethiopia, Pakistan, Russia, South Africa and the United States have in common and learn more about the critical components needed to achieve the eradication of TB.

Protecting Global Gains

Two new vignettes on Protecting Global Gains explore how communities are adapting to maintain critical healthcare as COVID-19 threatens hard-won gains in global health. This project is a collaboration including AVAC, Partners in Health, Friends of the Global Fight, Results, Treatment Action Group (TAG) and the Zero TB Initiative.

Protecting Global Gains: Innovation pays dividends against COVID-19 & TB in Karachi

The latest edition of Protecting Global Gains profiles how Karachi, the Pakistani mega-city of over 20 million people, took on the dual-threat of COVID-19 and tuberculosis (TB) by fitting mobile radiology vans with chest X-ray machines capable of screening for both infections, and adapting programs to support safer outreach.

Numerous predictive models quantify the devastating impact of COVID-19 on TB programming, including one that estimates TB-related mortality will increase by 20 percent in the next five years. Innovation pays dividends against COVID-19 and TB. This update from Karachi explores how public health leaders in the city are deploying infrastructure and expertise—honed from decades of TB programming—to tackle COVID-19 and safeguard valuable declines in TB incidence.

When Pakistan braced for a wave of COVID-19 infections in March 2020, the government shut down 12 mobile radiology vans that were offering TB screening in Karachi as part of the Zero TB Initiative-Karachi (ZTBI-Karachi), led by the Indus Health Network (IHN). But the shutdown contributed to a staggering 80 percent drop in TB detection. IHN sprang into action, developing methods and technology so the vans could get back on the roads and into the communities. The COVID-ready program offered simultaneous screening for TB and COVID-19 while following all infection-control protocols to minimize the risk of transmission. The innovation and adaptability reversed dangerous declines in TB case notification, almost bringing numbers back to pre-COVID levels, and continued connecting people at risk of TB or COVID-19 to prevention and treatment across the city.

This story from Karachi demonstrates one case where policymakers refused to choose between safeguarding global health gains or keeping down cases of COVID-19; with the right innovation and approach, both can be done. Other case studies, highlighted on the PGG website, show how health services rooted in community-centered, client-focused strategies are especially resilient, quickly solving problems, sustaining effective care, minimizing disruptions from the impact of COVID-19 and protecting lives.

Follow the Protecting Global Gains series on social media at @hivpxresearch, @theglobalfight, @Amref_Worldwide and #ProtectingGlobalGains, and consider amplifying these stories on your own social media. Advocates can call for national and international action to support the Global Fund’s COVID-19 response and for continued investment to end the TB epidemic. Visit to learn more about how to take action.

HIVR4P Virtual 2021—Prevention Unmasked: A roundup from week two

Last Friday marked the end of HIVR4P Virtual, and as AVAC reported last week, there are a number of excellent sources of news to catch up on all that was shared at the conference including coverage from aidsmap and Bhekisisa. In addition, AVAC roundups are available on our special HIV R4P page where you’ll also find recordings from the many great sessions hosted at the Advocates’ Corner, covering topics like vaccine hesitancy, research ethics, “the tail” in CAB-LA research and more. Consider checking out the Advocates’ Corner sessions you missed and continue the conversation on Engage!

Read on for a take on some of the key themes from the second week.

Prevention Unmasked: The second week of HIVR4P

by Emily Bass


Masks are omnipresent these days: a public health tool, a commodity that’s a given for some, a luxury for others and—in politicized environments like in the United States—a symbol of one’s relationship to science and even vaccines. Masks were on my mind as I attended the second week of HIVR4P. What’s on the surface, what’s underneath? These were the questions that recurred, or seemed to, throughout the second week. Here are some ways the complexities and challenges in the field today appeared to me.

The mucosa remain mysterious and critical to understanding early events in HIV

For all the decades of research on HIV, with increasingly sophisticated techniques, assays and approaches, there are enduring unanswered questions—especially about the earliest events following the acquisition of HIV. In the context of sexual transmission, these events occur at the mucosa—the lining of the vagina, rectum and penis. A presentation involving long-term follow-up of participants in the Thai vaccine trial known as RV144 provided insights into when and how vaccine “boosts” deliver immune responses at mucosal tissue—a site that wasn’t sampled in the original trial. Alexandra Schuetz reported the finding that participants who received the boost at 12 and 15 or 18 months after their last shot had stronger immune responses, including at mucosal surfaces, than those who received it at 6 months. The timing of follow-up shots, and their impact on the types and location of immune responses is another area where there’s still a lot to learn—in HIV, COVID and other research arenas. Other research described below homed in on how STIs harm, and lactobacillus helps, mucosal barriers that block HIV infection, and explored the possibility that infections might start and remain contained for some time in this region.

Community-based research and activism: “Inside out” and “Outside in”

There’s a tendency in many fields to draw a distinction between “researchers” and “community”—one that many AVAC partners help to disrupt and redefine. One invaluable contribution to this effort came in an R4P presentation on the place of Black researchers in French and American institutions, which are shaped by white supremacy. Tashuna Albritton presented findings from the ETOILE study (Experiences of Tensions in Organizations and Interventions Leveraged for Empowerment and Prevention), a Franco-American study evaluating the community of researchers. The presentation featured the perspective of one Black PhD candidate who said, “You can have the same degree and yet what you are contributing to the conversation is not considered as legitimate.” ETOILE yielded a plainspoken reality: en Francais or in English, Black researchers are given the most labor-intensive and time-consuming tasks, and work in white-dominated power structures (while R4P works diligently to reflect the diversity of the field in its panels and program, there were instances of white-dominated panels at this conference, too). In these hierarchies, white senior researchers select white collaborators more often than Black ones. The mere fact that Albritton presented this work at HIV R4P helped unmask racism within the organizations where research is designed and conducted. The next conference will be a chance to take stock of how the organizers absorbed the messages.

Challenging traditional structures and distribution of power was also central to talks by Clever Chilende (TALC, Zambia) and Jacque Wambui (NEPHAK/independent activist, Kenya), who described two successful civil society efforts to challenge and change the way that research teams engage with community.

The PopART trial, also known as HPTN 071, was a “treatment as prevention” trial that measured HIV incidence in communities in Zambia and South Africa. Participants were randomized to one of three trial arms—Arm A received a combination prevention intervention with universal ART initiation on diagnosis; Arm B included the prevention intervention with ART according to local treatment guidelines; and Arm C was standard care. Researchers compared the rate of HIV incidence in trial communities to incidence in communities where ART was provided according to national guidelines. PopART started before universal test and treat became standard; midway through the trial national guidelines changed, the trial design shifted and ART became available on-demand to people in both Arms A and B. In Zambia, Chilende and his colleagues pressed PopART investigators to engage people living with HIV (PLHIV) as activists, advocates and watchdogs. They pursued an “outside-in” approach, whereby civil society advocates worked with the trial team and study communities to create forums for input, research literacy and independent monitoring. “The outside-in approach has the potential to improve transparency and accountability at a range of stakeholder levels,” Chilende concluded.

Jacque Wambui went beyond the role of trial communities, in her presentation on civil society engagement related to the ECHO trial, which evaluated the impact of three contraceptive methods on HIV risk. Wambui described how a Global Community Advisory Group, or GCAG, was convened by the ECHO trial team. Comprised of women from the trial countries and other geographies, the GCAG worked in tandem with an independent advocacy working group that brought together advocates from a range of countries and disciplines to share information and build consensus on key issues related to contraception, HIV risk and choice-based programming. The interplay between the GCAG and the advocacy working group (jointly convened by AVAC and ICW-EA) helped build civil society power. On the GCAG, a small number of individuals consulted directly with the trial team, ensuring a wide array of voices contributed to the conversation. (In the interest of full disclosure, I was part of the GCAG and helped co-convene the advisory group with ICW-EA. I cheered on Wambui as I watched from my tiny home office, pumping my fist and shouting “Womandla!”)

Masks and partial, practical prevention

In my neighborhood, most of us wear masks, but in other parts of New York City and in many parts of the US, many people don’t. Now that COVID-19 vaccines have arrived for some people in this country—even as the epidemic sky rockets in many other countries—Americans are in the privileged, if delusional, position of having conversations about when things will go back to “normal”. In other words, they want to know when they can take off their masks. If the HIV field has offered clarity on anything, it’s that there’s no single solution to a global pandemic. No new technology is ever going to supplant the need for action on multiple fronts, whether it’s safeguarding the human rights of key populations—as Johns Hopkins professor Chris Beyrer so eloquently described in his talk—or offering a range of options, which as Ram Prasad of Final Mile said in an insight-filled talk about the prevention needs and perspectives of South African adolescent girls and young women, include not just condoms or PrEP or any biomedical option, but “trust,” “partner loyalty,” and, yes, ‘periods of abstention.”

No single technology will supplant an array of approaches and, as presenters described, new options will need to be tested in a world where there is a larger array of HIV prevention strategies than at any point in the history of the epidemic. In a satellite session on “next generation” trial design convened by AVAC and partners, advocates and researchers described what trials might look like in a world where all the options are on the table. Mike Robertson from Merck described the design of a pair of trials known as IMPOWER-22 and IMPOWER-24 that will test a once-monthly oral ARV called islatravir for PrEP. In both trials, participants will receive both a monthly pill and a daily pill; in one arm of each trial, the monthly pill will be the active drug islatravir and the daily pill will be the placebo, while in the other, participants will receive active daily tenofovir-based PrEP and a placebo monthly pill in place of islatravir. This double-dummy, double-blind design means that participants will not know whether they received islatravir or tenofovir-based PrEP.

Because oral PrEP reduces incidence when taken correctly and consistently, and monthly islatravir may as well, rates of new HIV diagnoses could be very low in both arms of the trial. As Robertson described, Merck is planning to use recency assays—which detect very early HIV infection—in the communities where the trials take place to estimate what incidence would be among participants, if they were not in the trial. Robertson said the recency assays drawn from the community is “the best way to estimate incidence,” since incidence is expected to be extremely low in the trials.

In the same session, Moupali Das of Gilead Sciences presented their plans for two efficacy trials of their six-monthly injectable Lenacapavir that will also rely on recency assays to estimate background incidence in the same communities and populations where the trial will be carried out. Participants who remain HIV negative at the end of the initial phase will be offered the chance to be randomized into one of the trial arms. One of these trials will be conducted among cisgender women to study both injectable Lenacapavir and oral T/TAF as PrEP. The second is studying Lenacapavir among men who have sex with men, transgender women and gender non-binary individuals.

Recency assays have implications for people who test positive—it may pinpoint from whom someone acquired HIV. This raises a host of questions and could entail the need for critical supports including provider training, communications for communities and individuals and monitoring of potential harms to individuals receiving recency test results and to their partners—who might be identified as sources of HIV infection. Particular attention will need to be paid to use of recency testing in contexts where laws that criminalize HIV exposure or transmission are on the books. As AVAC and amfAR wrote in an issue brief on new HIV testing strategies and human rights concerns, including the use of recency testing, “potential harms that can come with such testing [include] a false sense of security and potential misuse as evidence of transmission.” The AVAC-convened Advocates’ Trial Design Academy and other allies raised these concerns in early consultations with Merck about the islatravir trials; in those discussions, the drug company said that it was open to suggestions and recommendations. With 2021 launch dates for these trials, the time is ripe for civil society engagement, which might include ensuring that all trials using recency assays have documentation on the legal environment regarding HIV criminalization in relevant communities; adequately-resourced, independent community oversight; and specific, proactive approaches to documenting adverse events such as gender-based or intimate-partner violence, disclosure or other outcomes that might emerge from use of recency testing.

In other words, these new trial designs aim to get answers about the range of products people want and need—but it will only work if “outside-in” advocacy is a reality. Its work that’s going to be critical and complex, and AVAC and partners including the Advocates’ Trial Design Academy are committed to doing this work. (The consultations related to the F/TAF trial design were also presented during the first week of R4P by my colleague Daisy Ouya.)

PrEP unmasks longstanding questions about sexual pleasure and prevention of STIs

One of the most delightful and, yes, downright pleasurable sessions of week two was a round of “speed debates” on key topics related to PrEP, pleasure and other sexually transmitted infections. In studies of communities where PrEP use is climbing, rates of HIV are dropping. In many of these same communities, rates of STIs like chlamydia, gonorrhea and syphilis are climbing—a trend that was underway prior to PrEP but that may also be impacted by changes in condom use as people rely on PrEP for HIV prevention and/or by the increasing rates of testing that come with PrEP programs. PrEP doesn’t protect people against those and other sexually transmitted infections, which has had some people arguing that a PrEP-plus-condom message was the best public health approach. Wear condoms and avoid STIs, Edwina Wright said, arguing (in character for the sake of debate) that most women don’t enjoy sex with another person anyway. Understand that PrEP makes sex pleasurable for people—and pleasure must be at the center of sexual health programming, said Mitzy Gafos, Alongside preventing and treating STIs, Gafos argued that research and programs must go beyond condoms to support peoples’ full range of needs and priorities.

The debate was high-spirited, the stakes serious: as Gladys Macharia described, in a cohort of East and Southern African men and women (part of IAVI’s protocol C) having an STI increased the risk of acquiring multiple strains of HIV, versus a single founder virus. Infection with multiple strains of HIV was associated with a faster CD4 cell decline. Having an STI, and treating it, can also disrupt the vaginal microbiome, as Eric Armstrong described in a close look at how, exactly, lactobacillus helps keep the vaginal microbiome healthy. While STIs disrupt the vaginal epithelium, a protective layer of tissue, lactobacillus helps keep it robust, at least in lab-based tissue cultures. Lactobacillus also recruited anti-inflammatory immune responses—the kinds of defenses that may help the body ward off HIV on its own. As people use more PrEP and, sometimes, fewer condoms, the message should be, “Here’s how to get pleasure and be safe.” The specifics of that remain to be seen.

A debate on whether to abandon the WHO-endorsed “syndromic management” approach to STIs saw an audience poll overwhelmingly in favor of moving to an approach that treats “etiologically”. Syndromic management involves offering treatment for the most likely infection based on symptoms, while an “etiological” approach refers to precise treatment for a confirmed infection e.g., chlamydia. Whether this shift will happen, what it will cost and what it will look like remains to be seen—but prevention and treatment of STIs must be a part of the expanded PrEP rollout that will happen as new strategies become available.

Masks and the current pandemic moment

Since the beginning of 2020, masks have gone well beyond metaphor. They are life-saving, essential protections as the world faces down the global COVID-19 pandemic. Scientists and advocates are striving toward a dual agenda for HIV and COVID-19 during key sessions at HIVR4P and at a one-day IAS COVID-19 Prevention Conference, open to R4P attendees. It wasn’t always easy. A session at the COVID-19 conference featuring GAVI leader Seth Berkley, activist Fatima Hassan from South Africa’s Health Justice Initiative and Peter Sands of the Global Fund to Fight AIDS, TB and Malaria got quickly to the heart of the matter: like AIDS, COVID-19 is a pandemic of global inequities, defined by grotesque imbalances in access to COVID-19 vaccines, lack of transparency on pricing, and intellectual property provisions that, until waived, favor patent-holding corporations over people.

In a satellite session at R4P, HIV researchers looked at what they could learn from COVID-19 and vice versa. Galit Alter from Harvard Medical School urged the field to let go of the “herd mentality,” and start thinking outside the box. Linda-Gail Bekker from the Desmond Tutu Health Foundation leapt in to say she’d be beating the herd from behind—urging greater speed, in line with the toll AIDS still plays worldwide.

Masked infections: A new mystery from the AMP trial

In the final session on the final full day of the conference, a frank and fascinating exchange among scientists, during a discussion on the antibody-mediated prevention (AMP) trial, explored the possibility of “masked HIV infections” among participants in AMP. Here, the term refers to an infection that occurred while a trial participant was receiving the active experimental product, but that was not diagnosed while the person was using the product. How might that happen? See the very first item in this write-up about the mysteries of the mucosa.

The very early events of HIV infection are still not well understood, but in the context of sexual exposure, HIV starts in the genital tract and then moves—often via immune cells—throughout the body. It’s long been hypothesized that a prevention strategy or even the body’s own defenses might be able to contain HIV in the genital tract, preventing it from establishing infection throughout the body. If a drug or antibody played a key role in that containment, would HIV infection progress when those agents are no longer present? In such a scenario, someone who previously tested HIV-negative would now test HIV-positive. “We have data in the higher-dose VRC01 group—more cases occurred in the tail of the study than in the placebo arm,” offered Peter Gilbert from Fred Hutchinson Cancer Research Center.

One reason this might have happened, session moderator Carl Dieffenbach of NIAID said: VRC01 might have had “a weak antiviral effect.” In other words, the bump in what looked like new infections at the end, or tail, of the study in people who received VRC01 might have actually been the appearance, in the bloodstream of HIV that VRC01 had previously contained in a localized area, remaining undetected until VRC01 had washed out of the body. In intriguing new-to-me remarks, panelist Mike Cohen of the HPTN chimed in that masked infections might have happened in the CAB-LA trials, too. AVAC is following up to clarify and understand these hypotheses, but in that session, Cohen suggested that “masked infections” may be a reality in long-acting prevention. “That phenomenon almost certainly exists,” said Cohen, who went on to say that CAB-LA trials had 15 men versus and four women in the CAB-LA trials diagnosed with what he described as “a not-easily detectable infection.” Hearing investigators think aloud about what they’ve seen in trials—particularly what’s perplexing them—can be enormously revealing. In this case, there’s clearly far more to understand and learn.

Advocates have experience with the possibility of “false positive” HIV tests—especially in the context of HIV vaccine trials where the vaccine induces antibodies that cause a positive result on HIV-antibody tests. But a “false negative” is new terrain. What does the possibility of a false negative mean for informed consent processes, post-trial follow-up, the potential need for more sensitive HIV tests in the context of HIV programs, public health messaging, and community understanding of product efficacy? These critical questions began buzzing as soon as the session ended in an advocates’ debrief, and will be hashed out for months to come.

The AMP session also left open questions about how to use and describe the assay devised to study cases of HIV acquired among participants in the AMP study. That assay, known as the TZM-bl neutralization assay, involved sequencing the genes of viruses from participants, and then isolating genetic sequence encoding the envelope protein, known as “env”. The env sequences from participants were then used to form a new viral particle known as a “pseudotype”—which contains the isolated env sequence along with standardized, lab-adapted viral proteins. Making pseudotypic particles—in which the only difference is the env sequence—allows researchers to make controlled comparisons. In this case, the primary question was how the pseudotypes viruses from AMP participants responded to VRC01—whether the antibody neutralized it and, if so, at what concentration. The AMP investigators say that the trials validated the TMZ-bl assay as a means of predicting the breadth and potency of future bNAbs, or bNAb combinations, against a range of viruses. This predictive ability could be used to select bNAbs alone or in combination for future studies. Not so fast, said panelist Michel Nussenzweig, from the Rockefeller University who said that the field had to see AMP as “a disappointment,” and warned that for some bNAbs in development their ability to neutralize viruses was markedly different, depending on whether they were tested against pseudotypes or whole viruses, isolated and cloned from human samples. The investigators jousted back and forth about the relevance of the assay—settling for “both/and”—TZM-bl isn’t a total solution, but it’s an advance that moves the field a step in the right direction, if not across the finish line.

And that, in a way, is the best one can ask for right now—steps in the right direction, a realistic expectation of what a “finish line” might look like, and the understanding that we might still be wearing masks—real and metaphorical—on the other side. That’s especially true if the work doesn’t align with principles of justice and equity. In her talk last Wednesday, Dazon Dixon Diallo offered a quote from Paolo Freire, the anthropologist and theorist of inequality, that is as succinct and powerful a summation of this reality as any I know. And at the end of this roundup, of this most unusual conference in this most perilous time, Freire, via Dixon Diallo, has the last word: “Attempting to liberate the oppressed without their reflective participation in the act of liberation, is to treat them as objects to be saved from a burning building.”

HIV Prevention Research Report 2019

The annual report, HIV Prevention Research and Development Investments, which tracks funding in HIV research and development, has gone digital. The Resource Tracking for HIV Prevention R&D Working Group, a collaboration among AVAC, IAVI and UNAIDS, has launched a new website presenting 20 years of data and analysis. The website includes the latest information from the Working Group’s 16th annual analysis of HIV prevention research detailing overall investment and funding trends through 2019.

This new website offers a new tool for advocacy, with interactive analysis, and ready access to infographics. These tools can be used to advance advocacy for cutting-edge research and development and the scale-up of existing interventions needed to confront the ongoing HIV prevention epidemic, and build a stronger R&D foundation to address the COVID pandemic and whatever comes next.

Key Findings in Prevention R&D Funding

Funding is down, just a bit, but the trends are worrying.

This year’s report on 2019 data found a one percent decrease in total funding, erasing the modest 1.2 increase seen in 2018 after five consecutive years of declining investment. Total 2019 funding for HIV prevention R&D was US$1.13 billion. This incremental decrease impacted the various prevention categories differently. Investment increased for preventive vaccines and female condoms but decreased for voluntary medical male circumcision, microbicides, pre-exposure prophylaxis, prevention of vertical transmission, and treatment as prevention.

Despite these differences, donor trends remained similar to 2018. Public sector (80 percent of all funding at US$902 million) and philanthropic sector (14 percent of all funding at US$158 million, a 3 percent decrease) investments remained, for the most part, unchanged from 2018. The private sector saw a 5 percent decrease in investment, falling to 6.2 percent of all funding at US$70.6 million. Actual commercial investment levels are likely higher, as some private companies do not respond to the Working Group’s request for data.

Cautionary Lessons from COVID-19 Vaccine Investment

Unprecedented investment of over US$39 billion in 2020, and collaboration and global resolve helped catapult COVID-19 vaccines from testing to human use in just over a year. As of January 2021, seven vaccines have been authorized across dozens of countries with many promising candidates in the pipeline. The process of developing a vaccine against the SARS-CoV-2 benefited greatly from early research into an HIV vaccine. Yet, rapid development of COVID-19 vaccine candidates provide both an exemplary model and a caution. Rapid R&D development is possible with investment and political commitment. At the same time, the unacceptable inequity in access to COVID-19 vaccines—with a paltry amount available on the African continent—provides a lesson for the HIV field that R&D is just the beginning of the journey towards products that actually help end epidemics. Access makes these efforts meaningful—without it research has failed, no matter the trial result.

We hope the data and new website will serve as tools for advocacy, and inform public policy that accelerates scientific progress. We thank all of the individuals who contributed data to the report and those who, most importantly, gave time and effort as trial participants.

If your organization is a funder or recipient of HIV prevention grants and we don’t know you already, please contact us at!

HIVR4P Virtual 2021—Making Do With “Good Enough”: A roundup of the first week of HIVR4P

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.

As always, check out AVAC’s special webpage for the latest on all things R4P and IAS COVID-19 Prevention Conference.

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!