Islatravir, the first nucleoside reverse transcriptase translocation inhibitor, reaches levels in the body that should protect against HIV for at least a month, researchers reported at the 2021 HIV Research for Prevention conference. The drug is highly potent and has a long half-life, suggesting it could be taken once weekly for treatment and even less often for pre-exposure prophylaxis (PrEP). In an animal study, none of the monkeys that received high doses of islatravir were infected with an HIV-like virus. In an ongoing Phase II trial, people who took islatravir tablets once monthly for six months maintained protective drug levels in peripheral blood cells and in vaginal and rectal tissues. The tested doses were well tolerated. A pair of Phase III trials will now compare once-monthly islatravir versus once-daily oral PrEP for women and adolescent girls (IMPOWER-022) and for men who have sex with men and transgender women (IMPOWER-024). Researchers are also studying an islatravir implant that could provide protection for a year.