Lenacapavir, which was approved for HIV pre-exposure prophylaxis (PrEP) under the brand name Yeztugo in June 2025, has received much acclaim as a highly effective twice-yearly prevention option, but recent studies also demonstrate its promise for HIV treatment.

 

Lenacapavir for treatment, under the brand name Sunlenca, was first approved in 2022 for heavily treatment-experienced people with multidrug-resistant HIV. The Phase II CALIBRATE trial showed that it is also effective for first-line treatment. In 2023, researchers reported that up to 90% of previously untreated people randomized to receive lenacapavir injections every six months plus daily oral antiretrovirals had an undetectable viral load at 54 weeks. Final results published in October showed that nearly 100% of those who stayed on the treatment maintained viral suppression at 132 weeks.

 

There are currently no other equally durable antiretrovirals to build a complete twice-yearly treatment regimen, but broadly neutralizing antibodies (bnAbs) might fill this gap. Results from a Phase II trial, presented at the European AIDS Conference in October, showed that 89% of participants who switched from a standard daily oral regimen to lenacapavir injections plus IV infusions of two bnAbs, teropavimab and zinlirvimab, every six months maintained viral suppression for a year. What’s more, 76% of people who switched to the twice-yearly regimen said they preferred it to daily pills.

 

Lenacapavir also comes in an oral formulation. In November, Gilead Sciences announced top-line Phase III results from the ARTISTRY-1 trial, which is testing a new daily single-tablet regimen containing lenacapavir and the integrase inhibitor bictegravir (best known as a component of Biktarvy). The study enrolled more than 500 heavily treatment-experienced people on complex regimens containing up to 11 pills a day. Switching to the new combination pill was statistically noninferior to staying on a multi-tablet regimen, the company said.

 

Finally, oral lenacapavir lasts long enough that it doesn’t have to be taken every day. A Phase II trial is evaluating a once-weekly regimen of lenacapavir pills plus islatravir, an oral nucleoside reverse transcriptase translocation inhibitor from Merck. Last year, researchers reported that 94% of participants who switched from daily Biktarvy to lenacapavir plus islatravir had an undetectable viral load at 48 weeks. New results presented at the European AIDS Conference showed that 100% of those who stayed on the weekly regimen maintained viral suppression at 96 weeks. Gilead and Merck are now testing a lenacapavir/islatravir combination pill that could become the longest-acting regimen that doesn’t require injections.