Long-Acting Injectable HIV PrEP: Efficacy, Safety, and Injection Reactions

This episode, "Long-Acting Injectable HIV PrEP: Efficacy, Safety, and Injection Reactions," features the faculty comparing the two long-acting injectable PrEP agents in detail.

Dr. Cocohoba introduces long-acting cabotegravir, which reduced HIV risk by 66% and 88% relative to oral PrEP in the pivotal HPTN 083 and HPTN 084 trials. Dr. Urbina explains that drug-drug interactions are minimal, apart from strong CYP3A4 inducers such as rifamycins and certain antiseizure medications. The main tradeoffs are injection site pain and visit burden. Two loading doses one month apart are followed by injections every 2 months. That totals seven injections in the first year and six each year after. Dr. Cocohoba notes that the trials enrolled women, men who have sex with men, and transgender women, with supportive data in adolescents and pregnancy. Dr. Urbina adds that breastfeeding data are evolving but reassuring. He notes the indication covers sexual acquisition, not injection drug use.

Dr. Cocohoba then asks about lenacapavir and the PURPOSE 1 and PURPOSE 2 trials. Dr. Urbina calls the results remarkable, with no infections at the interim analysis among thousands of women and only a handful at study end. He cautions that lenacapavir is a moderate CYP3A4 inhibitor and substrate. Interactions with some recreational drugs and opioids therefore need review. Injection site reactions occur with both agents. With lenacapavir, subcutaneous nodules are common and persist, but they diminish with later injections.

Dr. Cocohoba notes that reactions in the HPTN trials were frequent but mild and usually resolved within 7 days. Dr. Urbina's team has also moved some injections to the thigh and seen fewer reactions. Dr. Cocohoba frames choice as central, since every patient weighs oral versus injectable and dosing frequency differently. Dr. Urbina presents options as a menu, for example after an STI diagnosis, and lets patients decide. He expresses confidence in both long-acting agents and credits skilled nurses for good outcomes.

In "What the CLARITY Study Means for Counseling on Long-Acting HIV PrEP," the faculty will assess a new crossover preference study and explain how its findings shape the way they counsel patients.