Tuesday’s CROI Roundup

March 6, 2024

Yesterday’s second full day at CROI 2024 in Denver included several studies presented on biomedical prevention, and the sum total of the message is clear: PrEP works, and choice works! Advocates have long called for choice—and now the science shows it works for individuals and supports declines in population-level incidence. Whether we’re talking about a daily pill of PrEP, injectable cabotegravir, or the dapivirine vaginal ring (DVR), from the US to Kenya, Australia to Uganda, people deserve choice! 

There was also more conversation about DoxyPEP, and how researchers and public health programs are balancing the public health benefits of reduced syphilis and chlamydia rates, with the threat of antimicrobial resistance, especially for gonorrhea.  

Here are highlights of the research!  

Tuesday’s Community Breakfast Club message, Living with HIV for a Lifetime—It’s Complicated, rang loud and clear.  

Allison Agwu from Johns Hopkins and Judith Currier from UCLA, talked about strategies presented on cross cutting health issues from cardiovascular disease to HPV that are affecting quality of life for PLHIV. And they talked about advances in treatment, such as the progress of long acting injectables, combination therapy with broadly neutralizing antibodies (bNAbs), and a long-acting pill—all of which are in the pipeline. 

But the advocacy around these field-changing issues echoes the very same priorities for HIV prevention, and the same priorities needed for global heath equity at large. Once new products are approved, they simply don’t reach the people who need them most, and offering choice is the key to reaching impact.  

“We are learning we have to figure out access in parallel with delivery. Clinics just can’t operationalize these innovations; we have to focus on this more and fund implementation science,” said Currier.    

“We need the a la carte of options. Something that fits in someone’s life now may not fit later,” said Agwu. 

The Breakfast session moderator, Annette Sohn from amfAR, talked about the advocacy still needed to ensure research is inclusive and data is gathered for all the populations that carry a disproportionate burden of HIV — another issue of great importance in HIV prevention.  “We still routinely have to tell researchers to stop combining data on men who have sex with men and transgender women.” For more on inclusive research for transgender people check out the The Transgender Manifesto.  

Evidence for making the most of prevention tools and the power of choice! 

Studies from three different continents delivered the message: enriched programs that support coverage and choice of prevention options will yield dramatic results.  

PEPFAR representatives pledged to take the findings of the SEARCH Dynamic Choice study into their programming decisions. Why? Just look at these results: Conducted in Kenya and Uganda, the study offered oral PrEP, PEP or injectable cabotegravir to both men and women, and an option to switch products. Prevention services were person-centered, including access to a clinician by phone at any time, clinic and community access to services, and counseling to develop personalized adherence plans. Coverage among study participants increased to 69.7% compared to 13% in the standard of care. Among people who self-reported HIV risk, coverage was 76%. Of the 56% who chose injectable CAB, 42% were not on any prevention product in the prior month. And perhaps most intriguing of all, 28% of participants used two different products during the study and the study arm ended with zero incidence of HIV compared to 1.8% in the control group—these numbers show why adding to the method mix expands the number of people who continue with prevention, even as their needs change. “CAB-LA is not simply replacing oral PrEP. It’s expanding the pie,” said Moses Kamya of Kampala’s Makerere University, who presented these data.  

Data from the INSIGHT cohort looked at PrEP uptake and continued use among more than 3,000 adolescent girls and young women in six African countries over six months. Participants who were shown test results measuring protective levels of PrEP in their bodies had higher adherence. The results: uptake was greater than 90%, at least 64% showed evidence of recent use. Investigators reported that “real time feedback” from these tests motivated adherence. 

In the US, a study conducted by Emory University suggests a direct link between population PrEP coverage and decreased HIV incidence. Between 2012-2021, PrEP coverage in the US ranged from 3.8% in West Virginia to 22% in New York, and rates of new diagnoses fell in association with increased coverage by state.  

Data from Australia analyzed HIV incidence among all people prescribed PrEP in Australia’s national PrEP program by tracking government subsidized PrEP prescriptions and antiretroviral therapy (ART) between 2018 and 2023. ART was used as a proxy for HIV acquisition, because both testing and treatment among PLHIV are high across the country. The data showed that low PrEP usage among gay men and other men who have sex with men, along with younger age and hepatitis C treatment was predictive of HIV incidence. Nicholas Medland who presented the data said “the overall incidence rate is low. As long as you can get PrEP out the door, it works at the population level.” 

The Deliver Study investigating efficacy of the dapivirine vaginal ring (DVR) among pregnant and lactating people (PLP) provided data from people in the second trimester of pregnancy. Building on earlier findings in later stages of pregnancy, investigators reported no increased rate of adverse outcomes compared to pregnancy outcomes in the community, and that “data support using DVR” as an HIV prevention option for PLP.  At this time, 11 countries have approved DVR, but this data is needed for regulators to approve its use for people who are pregnant. See our PrEP tracker for the latest on DVR initiations, regulatory approvals and more.  

DoxyPEP rollout: Ready? Or not? 

Yesterday we reported on DoxyPEP research, which showed reduced syphilis and chlamydia rates among MSM and TGW (though limited reductions in gonorrhea). There’s cautious optimism among researchers and public health programs about DoxyPEP, but questions remain about antimicrobial resistance (AMR) and whether expanding this intervention to cisgender women (where more research is urgently needed!) would further increase AMR globally. A round table discussion featured many angles.  

Chase Cannon from the University of Washington started with a history lesson—prophylaxis for STIs isn’t new. It was a program of the military in the mid-20th century for American soldiers but ultimately ended. Current data shows the clinical benefits of DoxyPEP. It reduces STI incidence significantly, it’s cost-effective and well-tolerated.  While concerns about AMR are real, taking DoxyPEP is less exposure to doxycycline than taking a full course to treat an STI. Alongside the clinical benefits, Cannon made the case that the community interest and uptake is hard to ignore. He pointed to qualitative research that DoxyPEP has played a transformative role in reducing stigma, sexual stress and anxiety in MSM.  

Beatrice B.S.L. Bercot countered with a more sober look, warning that AMR is already a problem in many European and African countries, and she’s cautious about wider global rollout. Her solution? “The damage is done” with gonorrhea drug resistance, the world has an urgent need for a gonorrhea vaccine. She also noted that while DoxyPEP is promising for syphilis and chlamydia, we need more surveillance and monitoring to better understand AMR spread. 

Stephanie E. Cohen from San Francisco’s Department of Public Health focused on implementation questions. She said DoxyPEP research and implementation is making the same mistakes made with PrEP—a lack of research for cisgender women and people assigned female at birth, and similar racial disparities in DoxyPEP use as seen with PrEP. Cohen cautioned that focusing on “risk categories” in marketing DoxyPEP may exacerbate disparities just as it did with PrEP.  

Cohen urged training for providers, marketing strategies that are non-stigmatizing, and new surveillance tools to monitor AMR. She called for better clinical guidance on STI screenings of people using doxy-PEP to identify other STIs. 

The rich data presented on Tuesday made clear the connection between science and the real-world. But Sunday’s opening session reminded advocates that many researchers who lead the science fail to understand that fundamental truth. During the Martin Delaney Lecture given by Frank Mugisha of Sexual Minorities Uganda, those who listened learned about the impact of draconian homophobic and transphobic legislation that is imperiling the lives LGBTQI+ communities in countries across Africa and in the US. To our dismay, many researchers attending the opening plenary chose not to listen. To learn more, please read this statement from the CROI Community Educator Scholars and Mentors, advocates and others who stand in solidarity.