December 5, 2020
Reviewed by Lauren Richey, M.D., MPH, FIDSA
Given the challenges to adherence to daily oral medicines for people with HIV there has long been interest in injectable long-acting medicines. Cabotegravir is an investigational integrase inhibitor that is a structural analog to dolutegravir, and rilpivirine is a non-nucleoside reverse transcriptase inhibitor currently approved in a pill form to treat HIV in combination with other medicines. Both have been formulated as long-acting injectable agents. FLAIR and ATLAS are two ongoing randomized, open-label, phase 3 studies, and the pooled results were recently reported in the Journal of Acquired Immune Deficiency Syndrome.
In the FLAIR study, participants received a fixed dose of oral abacavir, dolutegravir, and lamivudine once daily for 20 weeks before being randomized, if virally suppressed, to either injectable long-acting cabotegravir and rilpivirine or to stay on the oral regimen. Participants in the long-acting injectable arm received 4 weeks of oral cabotegravir and rilpivirine as a lead-in. In the ATLAS study, virally suppressed patients were randomized to stay on their current antiretroviral therapy or start cabotegravir and rilpivirine as a long-acting injectable after a 4-week oral lead-in with those medicines. Baseline characteristics were similar in the studies, which together had 1,184 people with HIV randomized. At 48 weeks both groups had 2% of participants with viral loads over 50 copies/mL, indicating noninferiority. The 48-week results also showed 93% of the cabotegravir/rilpivirine group were virally suppressed versus 94% on the oral antiretroviral therapy. Injection site reactions, nasopharyngitis, and headache were the most common side effects.
A cabotegravir and rilpivirine regimen given by long-acting injection is a novel way to treat HIV. It remains to be seen whether virologically suppressed patients will be interested in an injectable regimen and whether current clinic infrastructure can support monthly visits for injections. More data is needed on whether this regimen would be as efficacious in patients without virologic suppression and in patients with poor retention in care as the regimen requires more clinic visits.