The HIV PrEP Toolbox: Oral Options, Strengths, and Limitations

In "The HIV PrEP Toolbox: Oral Options, Strengths, and Limitations," the faculty map the current PrEP landscape and take a close look at daily oral regimens.

Dr. Cocohoba asks Dr. Urbina to lay out the current PrEP landscape. He begins with the first-generation oral nucleoside reverse transcriptase inhibitor combinations. These are tenofovir disoproxil fumarate with emtricitabine and tenofovir alafenamide with emtricitabine. Long-acting options followed, drawing on familiar HIV treatment classes. Cabotegravir, an integrase strand transfer inhibitor approved for prevention in 2021, is a gluteal intramuscular injection given in clinic. Lenacapavir, a capsid inhibitor first approved for treatment, gained its prevention indication in 2025 based on the PURPOSE trials. It is a subcutaneous injection dosed every 6 months, and its volume makes self-administration impractical. That brings the toolbox to four options, and an annual intramuscular lenacapavir formulation is on the horizon.

Turning to oral PrEP, Dr. Urbina describes its strengths. It is very well tolerated, has few side effects, and is familiar from HIV treatment. Tenofovir disoproxil fumarate carries concerns for renal function and bone health. The alafenamide formulation reduces those issues but is not indicated for receptive vaginal exposures, so it is not an option for cisgender women and transgender men. The disoproxil formulation has broader use, including for people who inject drugs. Dr. Cocohoba adds that the disoproxil combination has good data for event-driven, or 2-1-1, dosing. Dr. Urbina cautions that two doses must be taken 2 to 24 hours before sex, which people cannot always anticipate. Dr. Cocohoba notes the event-driven data come from men who have sex with men and transgender women.

The biggest limitation, both faculty agree, is the daily pill itself. Dr. Urbina notes that protection requires at least 4 doses weekly and that perhaps half of patients stop. He also flags chronic kidney disease, dehydration, substance use, and hepatitis B flares after discontinuation.

Our next episode, "Long-Acting Injectable HIV PrEP: Efficacy, Safety, and Injection Reactions," turns to long-acting cabotegravir and lenacapavir, including pivotal trial results, drug interactions, and practical ways to reduce injection site reactions.