The 2022 Conference on Retroviruses and Opportunistic Infections (CROI) concluded last week with dynamic sessions that put a spotlight on where and how HIV prevention must do better. It’s no surprise to many advocates that the answers involve a comprehensive commitment to informed choice, comprehensive & integrated responses, and the central importance of community-led interventions. These themes could be found throughout sessions from both weeks of CROI. Check out our highlights from week one for updates on the Dapivirine Vaginal Ring (DVR), injectable cabotegravir (CAB) for PrEP, vaccine science, cure research and more. And read on for highlights from the second week of CROI and from the Margarita Breakfast Club (check out the full MBC program and recordings here).

Week two of CROI covered key topics such as pioneering research on prevention of sexually transmitted infections, strategies to reach key populations, and the all important priority of choice at this historic juncture when two new HIV prevention options have been approved, the ring and injectable CAB.

CHOICE CHOICE CHOICE

The symposium, Bringing Choice in HIV Prevention, looked closely at how investing in healthcare systems, enhancing trust in providers, and offering an array of effective choices could meaningfully overcome some of the most significant barriers to delivering HIV prevention at scale.

Hyman Scott from the San Francisco Department of Public Health pointed to 2021 data from the US, where oral PrEP use is among the highest in the world, showing that only 25 percent of the population eligible for PrEP is using it. Those numbers plummet for women (10 percent), and for people who are Black (9 percent) or Latino (16 percent). Hyman said providers play a pivotal role as people seek an affirming, non-judgemental encounter with providers and look for them to “open the door to improve their engagement around their sexual health needs.” If those providers then connect people to real choices, it’ll lead to major advances in HIV prevention. Hyman also discussed data from a two decade study on contraception use, showing that each new option was associated with 4-8 percent increase in uptake. Data from the REACH Study, referenced in Scott’s presentation and in our round up from the first week of CROI, showed that people will act on diverse preferences for different forms of HIV prevention if given the opportunity.

Dominika Seidman from the University of California San Francisco offered another model from the field of contraception, a history lesson, and a warning. As long-acting contraceptives became available, a protocol referred to as “tiered effectiveness” instructed providers to emphasize efficacy above all else. Seidman reported that this method fueled mistrust as women experienced providers pushing one method over another. “The family planning world has been playing catch up ever since.”

Seidman offered three models for provider counseling, and flagged a clear favorite. “Method promotion” prioritizes one product based on its characteristics. “Informed choice” offers a menu of options with no guidance on how to choose among them. Seidman laid out the advantages of a third model for provider counseling, “shared decision-making”. Seidman said under this approach, providers offer information, elicit user preferences, facilitate decision-making, leave the door open for changes in plans and priorities, and foster trust in the relationship and in the broader health-care system. “Effectiveness is not the only variable people care about, in some cases it’s not even the primary one,” said Seidman.

The presentation by Kenyon Farrow of PrEP4All echoed the role of choice and the urgent need to establish trust between the users of HIV prevention and providers. “We have a trust problem and it’s getting worse,” said Farrow pointing to US data on the loss of public trust in health authorities since 2009. “We need to invest in this as much as in research and development.” Farrow called for research on practices that combat misinformation, more comprehensive efforts to demystify clinical research, greater support in navigating health systems, innovative public health campaigns, expanded community advisory bodies, and deep investment to improve the relationship between people and their providers.

STIs Are Part Of The Picture, Too

CROI 2022 put renewed attention on the six-year trend of increased sexually transmitted infections seen in the US and other countries. At the symposia, Sexually Transmitted Infections: Reversing the Tide, presenters explored the intersection with HIV prevention and provided updates on research in STI vaccines and drug-based prevention.

Leandro Mena of the US Centers for Disease Control and Prevention shared recent US data, where surveillance is strong, showing, for example, gonorrhea is up 10 percent since 2019 and 44 percent since 2016. And syphilis is up 3 percent since 2019 and 52 percent since 2016.

Sinead Delany-Moretlwe of Wits RHI in South Africa, in a presentation on the case for STI vaccines, said one million cases a day of curable STIs burden people, communities and governments. HIV and other STIs are tied to the same risk factors. An STI, in and of itself, increases the likelihood of HIV infection. But even more compelling, obtaining prevention or treatment for an STI is a critical opportunity for someone to be connected with HIV services for prevention or treatment.

The message from the session moderator, Connie Celum of the University of Washington: attention to better STI prevention is long overdue. What’s needed are better diagnostics, continued commitment to research on vaccines and anti-microbial prevention strategies, and access to affordable and integrated services in non-traditional settings. To be effective, interventions must go beyond past approaches, develop a paradigm where overall health and well-being are at the center of the response. “That’s the key to turning around the increase in STIs” said Mena.

The US launched its first STI national strategic plan in 2020, and its emphasis on raising awareness and making screening and treatment more accessible are a step on this path, more tools and advocacy for a community-led response remain urgent. Among those needed tools are vaccines. Delany-Moretlwe provided an update on the STI vaccine pipeline.

Lessons from a three dose vaccine for human papillomavirus (HPV) first approved in 2006 offered important context. Though highly effective, fewer than 5 percent of countries have succeeded in reaching target numbers of people at risk with the three dose vaccine, with delivery challenges hampering uptake. Delany-Moretlwe said research is moving in the right direction with several studies showing efficacy with a single dose HPV option, expected to be simpler to deliver. WHO is reviewing that data now. In addition, a host of studies are looking at therapeutic HPV vaccines. But effectiveness will not be decided by the efficacy seen in the data. Product attributes, such as the dosing schedule, will be critical considerations for any product to reach those who need it.

Delany-Moretlwe also described a proof-of-concept study for a gonorrhea vaccine that was developed after researchers saw a protective signal for gonorrhea from a meningitis vaccine. Further studies are underway. When it comes to herpes (HSV), a trial that reported findings in 2012 on a preventive vaccine showed no protection against disease. Since then, investors have shown more interest in the potential of therapeutic vaccines for HSV. Vaccines for other STIs, such as chlamydia and syphilis are not as far along, struggling with funding and questions of trial design.

Research on drug-based prevention for STIs is also underway. Elizabeth Bukusi from the Kenya Medical Research Institute discussed the potential of doxycycline as an STI PrEP or PEP, which is under investigation in several studies. Key questions remain including: the impact on HIV risk, the effect of doxycycline on people living with HIV, the drug’s impact on the vaginal and gut microbiome, and the risk of antimicrobial resistance. In answer to these important concerns, Bukusi said, “We need data on all these questions. We have to do the work to find out what will work and for whom. We have to find the answers. And then we have to implement, at scale.”

Paving The Road To HIV Prevention For Key Pops

The barriers to HIV prevention for sex workers, transgender people and people who use drugs remain overwhelming. A sample of HIV prevalence statistics tell the story: for transwomen the global average is 19 percent; for female sex workers in Zimbabwe it’s 52 percent by age 24. People who inject drugs have a global HIV prevalence of approximately 13 percent. The presentations in the symposium HIV Prevention in Special Populations showed a fundamental need for more data to answer a range of essential questions to finally reach these key populations with HIV prevention. For example, most health surveillance systems do not collect sex and gender data, the population size of trans communities is poorly documented, literature is just emerging on how people who inject drugs are engaging with PrEP, and little is known about how the life stage of a person engaging in sex work affects their relationship to prevention services.

A few key issues stood out: Sari Reisner, from Brigham and Women’s Hospital, highlighted the cross-cutting impact of gender affirming care as a central component to effectively offering HIV prevention services to transgender people. For more on this and other priorities for a transgender research agenda check out No Data No More: Manifesto to Align HIV Prevention Research with Trans and Gender Diverse Realities, written by by trans and gender-diverse global activists, with support and solidarity from AVAC. Reisner said gender affirmation demands a personalized approach that can encompass social, medical, legal and psychological factors that will be different for each individual.

Frances Cowan, from the Liverpool School of Tropical Medicine, reported on growing evidence that stigma, food insecurity and discrimination isolate sex workers who remain poorly engaged with HIV prevention and care services. But here again, the transformative and essential role of peer-led community based approaches was evident. A meta analysis of community based interventions, reported by Cowan, showed they not only improve the lives of sex workers, but improve their engagement with care. However the data is sparse on long-term outcomes. Cowan’s presentation also included the successful example of Ashodaya Samithi PrEP demonstration project, a sex worker-led initiative in Mysaore India. Self-reported PrEP adherence, confirmed by blood tests, was 80 percent or better.

Cowan’s final remarks addressed what has worked in Zimbabwe’s effort to bring PrEP to sex workers, and they reinforced the priorities AVAC has been calling for as loud as we can. What worked: Peer leadership, diverse places to access PrEP including home delivery and community drop-in centers, multi-month dispensing, and integration with STI and sexual and reproductive health services. And the final component we hope is just around the corner: adding to these peer-led community-based services, an array of proven options from which one can choose.

Looking forward to working with you all to help make this happen.