PrEP
Long underrepresented in HIV prevention research, cis women have become more visible in recent clinical trials with significantly favorable results this past year. Still, women face issues with PrEP uptake, adherence and persistence, said Dr. Agwu. They have Truvada (F/TDF) and Apretude (cabotegravir LA) as prevention options; however, Descovy (F/TAF) is not approved as PrEP for cis women and the dapivirine vaginal ring has not been approved in the U.S. “Additionally, we do need modalities that better fit cisgender women’s varied preferences and needs, and we need options for pregnant women,” she said.
Gilead’s PURPOSE 1 trial, however, has shown great promise for lenacapavir (LEN) for cis women (see “Injectable lenacapavir 100% effective at preventing HIV in cis women,” SEP+OCT 2024). Presented at AIDS 2024 and in the New England Journal of Medicine, the study looked at the efficacy of LEN, an HIV capsid inhibitor given twice yearly, subcutaneously, compared to oral F/TAF for HIV prevention. Cis women between the ages of 16 to 25 who were not on PrEP and HIV-negative were randomized into groups given LEN subcutaneously every eight weeks with oral F/TAF placebo or TDF placebo. The second arm was F/TAF, oral daily versus subcutaneous LEN. The third arm was F/TDF. In the study, all participants were Black, 84% from South Africa and 16% from Uganda, and very few had ever been on PrEP. The results, which got a standing ovation at IAS 2024, showed zero infections in the LEN arm, or 100% efficacy. All PrEP arms were safe and well tolerated. Importantly, Dr. Agwu added, participants who became pregnant during the study were given the option to remain in the study, “with the idea of protecting people, not excluding them, through research.”
Results from the PURPOSE 2 trial, which looked at PrEP for cisgender gay, bisexual and other men, transgender women and transgender men and gender nonbinary individuals who have sex with partners assigned male sex at birth, had similarly stellar results for that population. There were substantial decreases in HIV acquisition, and only two HIV acquisitions in the LEN arm, and nine in the F/TDF arm, compared to the background incidents. Being a global study was significant, she said, as well as the fact that the majority of participants were non-white. “Only one in four had ever been on PrEP, and only one in four had no prior HIV testing. And there was a lot of stimulant use, which is a risk factor for HIV acquisition.”
“We need expansion in prevention strategies, period,” she said, noting that 1.3 million individuals acquired HIV in 2023 across the world, including 30,000 in the U.S. In early October Gilead announced licensing agreements with six drug companies to produce and sell a generic version of lenacapavir in 120 countries, including in Africa; however, many countries in Latin America, one region of the world that is seeing an increase in HIV, were left out of the agreements.
Long-acting injectables (LAIs) for treatment
Results from MOCHA (More Options for Children and Adolescents) were presented at CROI 2024 in March. MOCHA, a multi-center, open label, non-comparative study, part of IMPAACT 2017 (International Maternal Pediatric Adolescent AIDS Clinical Trials), looked at injectable cabotegravir (CAB) for adolescents 12–17 years, a group known to be less likely to adhere to antiretroviral treatment (ART), across the U.S. and several countries, including Thailand, Botswana and Ghana.
In results from the first cohort, published in The Lancet this past summer, 55 participants who remained on their background combination antiretroviral therapy were started with injectable CAB (30) or oral rilpivirine (25). Using the six-point face scale for pain, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported no or little pain from the injections, and a single (2%) participant for each week rated the pain at one of the two highest pain levels.
Results from cohort two, presented at CROI 2024, included 44 rolled over from the first cohort, with an additional 100 new enrollees. In this phase, participants stopped oral ART and went on injectables. This group had a median age of 15, about half were cis female; three out of four participants were African American. The vast majority (92%) had acquired HIV perinatally. The 48-week data presented at AIDS 2024 showed no unexpected safety events and virologic suppression was maintained. Participants cited convenience and, to a lesser extent, stigma reduction, as reasons they preferred long-acting injectables (LAIs). “Nobody wanted to go back to oral ART,” Dr. Agwu said.
IMPAACT 2036 will test long-acting injectables in children ages 2–12 years, she said, and IMPAACT 2040 will study injectables for pregnant women, “so more options to assure people can maintain viral suppression.”
Results from the LATITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life) study were presented at CROI 2024. The study looked at participants with poor viral response despite being on oral ART for more than six months, or oral ART non-adherence for more than six months. The median age was 40, and about 20% were under the age of 30. Significantly, 26% were over the age of 51, showing the “silvering” of the HIV epidemic, she said. At 52 weeks the study showed significantly fewer virologic failures (7.2%) in the CAB arm versus 25% failure using the oral standard of care.
Maintaining health with ART and beyond
Dr. Agwu acknowledged a 2024 report which supported breast and chest feeding choices for people living with and with a greater chance of acquiring HIV, which follows similar guidelines from the World Health Organization and the Centers for Disease Control and Prevention (CDC). “This is critically important because people continue to be stigmatized and this is an additional tool to be able to use to push back from that.”
Using the six-point face scale for pain, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported no or little pain from the injections
For adults with perinatally-acquired HIV, the good news is that rates have been decreasing, and mortality in this group has declined. However, because the majority of people who acquired HIV perinatally are older than 25, and “have unique aging profiles and comorbidities that we have yet to understand, we need to assess what and how to address this population,” she said. A 2024 study of non-AIDS-defining comorbidities among young adults with perinatally-acquired HIV found that by the age of 30, about one in three had type two diabetes, about half had hypertriglyceridemia (high levels of fats that provide energy to the body, but are a risk factor for cardiovascular disease) and one in three had chronic kidney disease. “So, significant cumulative incidence of non-AIDS-defining conditions.”
This is important in light of updated guidelines from the U.S. Department of Health and Human Services (HHS) on statin therapy for adult and adolescent people living with HIV. “The findings from REPRIEVE [a study to reduce heart disease in PLWH] related to the higher absolute benefit of statin therapy among those with greater [atherosclerotic cardiovascular disease, ASCVD] risk informed the panel’s decision to recommend the use of at least moderate-intensity statin therapy with a strong recommendation for those with 10-year ASCVD risk score equal to or greater than 5% to less than 20%,” state the new HHS guidelines.
Advocacy and funding priorities: Tennessee as a cautionary tale
In a segue to advocacy and money, Dr. Agwu warned the audience that the HIV community is facing continuous attacks on funding, meaning “the progress we’re making with all the things we’re talking about could be at risk.”
To emphasize this threat, she pointed to research published in the June 2024 issue of Clinical Infectious Diseases that showed how Tennessee’s new policy of shifting funding for HIV prevention could lead to more illness, more deaths and higher costs.
In January 2023, the state rejected $6.2 million in funding from the CDC for prevention tools like HIV testing kits, condoms and PrEP, which had been prioritized for groups who are seeing higher rates of HIV, such as men who have sex with men, transgender women, people who inject drugs and heterosexual cisgender Black women. Instead, Tennessee planned to reallocate funding for HIV testing to three other groups: first responders, pregnant women and survivors of sex trafficking—populations that represent a tiny population of people vulnerable to acquiring HIV.
Massachusetts General Hospital analyzed the effects of this reallocation, using a computer-based simulation model called Cost-Effectiveness of Preventing AIDS Complications (CEPAC) to predict outcomes statewide.
The team of researchers found that shifting funding away from CDC-prioritized populations would result in an additional 166 HIV transmissions, 190 deaths and 843 life-years lost over a decade. Led by Ethan Borre, MD, the researchers also determined that the change would increase costs to the state by 1,300%, or $4.1 million. In a press release, Borre said Tennessee’s HIV funding reallocation would “worsen existing disparities with minoritized populations experiencing a lion’s share of increased deaths.”
“What you saw in this analysis would be decreased virological suppression, decreased linkage to care and fewer individuals biologically suppressed, and would prevent zero HIV transmissions in the Tennessee priority populations,” Dr. Agwu said. From 2018 to 2023, Tennessee reported a 40% increase in HIV transmission among people ages 15–19 years. “So we have to match what’s happening on the ground with our funding,” she said.
An epidemiological study released in May 2024 by the Tennessee Department of Health underscored this analysis, stating that that non-Hispanic Black people faced the highest burden of HIV across all gender and age groups in the state, and that 14% of new diagnoses occurred among people who inject drugs.
She ended on a hopeful note, telling participants to be calm but vigilant, especially in the face of proposals from Republicans in the U.S. Congress to slash hundreds of millions from federal HIV programs. “Please tell Congress to save HIV funding.”