Long-acting injectable HIV treatment and PrEP (medication to prevent HIV) continue to be areas of interest and progress in the HIV field. Some of the latest research on injectable treatment and PrEP was presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) earlier this month and we have put together some highlights below.
The first study of injectable HIV treatment in Africa has found it was just as effective in maintaining viral suppression as standard oral antiretroviral therapy. The Cabotegravir and Rilpivirine Long-Acting in Africa study (CARES) recruited 162 participants in Kenya, 106 in South Africa and 244 in Uganda. They received either the integrase inhibitor cabotegravir and the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine as an intramuscular injection every eight weeks or the standard oral medication offered in the country they live in.
The proportions in each group with a viral load below 50 at week 48 were almost identical: 96.9% in the injectable treatment group and 97.3% in the standard treatment group. Presenting the study results, Professor Nicholas Paton said the findings were an “essential first step in discussing the role of injectable cabotegravir and rilpivirine, but there are so many things we need to do before this would translate into a World Health Organization public health recommendation.”
Studies presented at the conference found that treatment with cabotegravir and rilpivirine injections monthly or every other month can be an effective option for people who have difficulty maintaining adherence to daily oral treatment. In Europe and the US, approval for injectable cabotegravir and rilpivirine is limited to people who already have viral suppression on antiretroviral therapy (ART) and have no history of treatment failure and no resistance to either drug. But for some people who find adherence difficult, long-acting treatment may be a better option.
The phase III LATITUDE trial gave people intensive support to achieve viral suppression on a daily oral regimen before switching to cabotegravir and rilpivirine injections. In another study, people who had difficulty taking pills consistently were offered injections as an alternative despite having detectable viral loads. Professor Aadia Rana of the University of Alabama at Birmingham said, “Offering an effective alternative for people who have struggled with taking daily ART could provide life-changing freedom from the stress of unsuppressed HIV.”
Early study results presented at CROI suggest that a longer-acting formulation of cabotegravir may offer an option for HIV treatment and PrEP that could be administered once every four months. The small phase I trial showed that the new ultra-long-acting formulation given by subcutaneous or intramuscular injection every four months achieves comparable drug exposure but lasts longer in the body than the approved formulation administered every two months.
Two long-acting antiretrovirals, lenacapavir and cabotegravir, could be paired with broadly neutralising antibodies (bnAbs) for HIV treatment. These specialised antibodies are being explored for HIV prevention, treatment and cure research. The results from a study of lenacapavir plus the two bnAbs teropavimab and zinlirvimab were presented, with eight of ten participants maintaining viral suppression on the combination after 26 weeks. It is now going to phase II trial. A second study evaluated the safety and efficacy of long-acting cabotegravir plus a bnAb called VRC07-523LS. All but five of the 60 participants who completed the study maintained viral suppression at 48 weeks.
Researchers in Kenya and Uganda have demonstrated the benefit of offering people a choice between PrEP pills and PrEP injections. The programme has already successfully demonstrated that offering a person-centred HIV prevention intervention which gives people a real choice of options and ways to access services results in significant increases in the numbers of people covered by PrEP or PEP. The programme showed that when services were offered in the usual way, a minority of people used oral PrEP or PEP. When services were optimised to provide choice and flexibility, uptake more than doubled.
In the latest stage of the randomised study, reported at CROI 2024, people were offered PrEP injections as an additional option. With this option, 70% of people used some form of biomedical HIV prevention. Notably, of those who started injectable PrEP at the beginning of the study, 42% hadn’t been using any form of HIV prevention in the month before.