Raphael J. Landovitz, M.D., on rare PrEP breakthrough infections | AIDS 2026

Rare breakthrough HIV infections in people taking lenacapavir, the twice-yearly injectable pre-exposure prophylaxis (PrEP) option, have shown viral loads far higher than researchers saw with earlier breakthroughs on injectable cabotegravir, raising new questions about how often patients on long-acting PrEP should be tested between doses, according to Raphael J. Landovitz, M.D.

Landovitz, professor of medicine and chief of the division of infectious diseases at the David Geffen School of Medicine at UCLA and director of the UCLA Center for Clinical AIDS Research and Education, will deliver the plenary lecture "PrEP 2026: State of the Art" at AIDS 2026, the 26th International AIDS Conference, in Rio de Janeiro.

In this interview with Managed Healthcare Executive, Landovitz walks through why he believes testing cadence deserves more attention as PrEP dosing intervals stretch to six months or longer and why he is wary of dismissing rare breakthrough infections as not worth "machinating about" simply because they occurred infrequently in clinical trials. Real-world use at scale, he said, will be the true test of how often those events show up outside a controlled trial setting.

Five breakthrough infections have been reported in the public domain across the PURPOSE 1 and PURPOSE 2 lenacapavir trials, Landovitz said, and some of those cases presented with viral loads above 100,000 copies. That contrasts with the rare breakthroughs seen earlier with cabotegravir, where viral loads were characteristically very low, a pattern researchers came to call “low-level viremia.” The higher viral loads seen with lenacapavir raise the possibility that someone could be walking around for months with resistant virus and a high potential for secondary transmission before a scheduled injection visit catches it, Landovitz said.

He connected the question to older data on testing intervals for sexually transmitted infections (STIs) among people on daily oral PrEP. The Centers for Disease Control and Prevention previously modeled that quarterly STI testing, timed with the three-month visits typical of oral PrEP dispensing, could interrupt ongoing transmission by catching asymptomatic infections earlier, Landovitz said. More recent data out of Europe, particularly on gonorrhea among men who have sex with men, suggests that less frequent testing, at six- or 12-month intervals, can reduce antibiotic use without increasing transmission rates.