The Conference on Retroviruses and Opportunistic Infections (CROI 2024) took place this month. Researchers presented work on new and existing HIV treatment options. Here are some of the highlights.
In a large clinical trial in Africa, injectable HIV treatment proved as effective in maintaining viral suppression as standard oral antiretroviral treatment. The regimen used was the integrase inhibitor cabotegravir and the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, which is already approved for use in Europe and North America. The study recruited 162 participants in Kenya, 106 in South Africa and 244 in Uganda and they received either the injectable treatment every eight weeks or the standard oral treatment offered in their country. At week 48, the proportions of people in each group with a viral load below 50 were almost identical: 96.9% in the injectable group and 97.3% in the standard oral treatment group.
As well as long-acting injectable treatment, long-acting oral HIV treatment was also discussed at CROI. Study results showed that a once-weekly oral regimen of lenacapavir and islatravir can keep HIV suppressed as effectively as daily pills. Lenacapavir, from Gilead Sciences, is the first HIV capsid inhibitor and islatravir, from Merck, is the first nucleoside reverse transcriptase translocation inhibitor. A phase II study enrolled 104 adults with HIV who were taking daily Biktarvy (bictegravir/tenofovir alafenamide/emtricitabine) and had a suppressed viral load. The participants were randomly assigned to either continue taking Biktarvy or to switch to taking 2mg islatravir plus 300mg lenacapavir pills once a week. At 24 weeks, both groups had the same rate of viral suppression (94.2%) after accounting for five people with missing data.
Two other antiretrovirals with the potential for once-weekly oral dosing have undergone phase I studies. MK-8527, a new nucleoside reverse transcriptase translocation inhibitor is being developed by Merck as a once-weekly drug for HIV treatment and a monthly drug for PrEP. The second antiretroviral, GS-1720, is a once-weekly integrase inhibitor taken orally, being developed by Gilead Sciences.
Several presentations at CROI 2024 addressed whether HIV is starting to develop resistance to the integrase inhibitor dolutegravir, one of the most widely used antiretrovirals in the world. In World Health Organization guidelines, dolutegravir is the cornerstone of first- and second-line HIV treatment. Because it is so widely used, it is important to monitor for any sign of an increase in dolutegravir-resistant HIV. The conference heard that significant dolutegravir resistance is still uncommon, but it has become more common, and certain groups, including children, seem more prone to it.
A retrospective cohort study in the US reported that switching to an integrase inhibitor around the time of the menopause was associated with accelerated weight gain in women with HIV when compared to pre-menopausal women with HIV. This study included 424 women with HIV who switched to an integrase inhibitor, 733 who did not, and a control group of 994 women without HIV. Whereas switching to an integrase inhibitor did not seem to accelerate weight gain before the menopause, it did speed up weight gain as women with HIV reached the menopause. The study investigators say that menopausal status should be considered before switching to an integrase inhibitor.