Once-weekly pill matches daily oral HIV treatment in phase 3 studies

.AIDS 2026 | Rio de Janeiro.

A new once-weekly pill combining two antiretroviral drugs, islatravir and lenacapavir, appears to be as effective as daily oral medication at treating HIV, according to interim study findings presented ahead of the AIDS 2026 conference in Rio de Janeiro, Brazil.

At a press conference preceding AIDS 2026, Amy Colson, MD, MPH, principal investigator for two large multicountry studies—ISLEND-1 and ISLEND-2—presented 48-week phase 3 data from both studies, which tested the efficacy and tolerability of once-weekly oral HIV treatment.

The bottom line: the weekly oral pill was well tolerated and worked as well as standard daily therapies.

The two-drug combo is a collaboration between two drug companies. Islatravir (ISL) was developed by Merck & Co. (the U.S. and Canadian name for the international pharmaceutical Merck Sharp & Dohme, or MSD); Gilead Sciences developed lenacapavir (LEN). Hence the studies’ play on the drugs’ abbreviations, ISLEND.

Gilead is sponsoring the studies, which will continue until 96-week results are complete. If approved by the Food and Drug Administration (FDA), the new weekly pill would be the first long-acting HIV treatment in pill form. While ISL/LEN has not yet been submitted for FDA approval, the promising phase 3 ISLEND results will likely be used as the basis for its new drug application as a weekly HIV oral treatment.

A complete long-acting injectable regimen for HIV has been available in the United States since 2021, when ViiV Healthcare’s combination of cabotegravir and rilpivirine (brand name Cabenuva) was approved. In December 2022, Gilead’s injectable form of lenacapavir was approved as a component of HIV treatment (under the brand name Sunlenca) for heavily treatment-experienced adults with multidrug-resistant HIV; lenacapavir was approved as a standalone injectable for HIV prevention (PrEP), marketed as Yeztugo, in June 2025.

A once-weekly oral ISL/LEN would expand treatment choices while offering less-frequent pill taking, which could improve convenience and support long-term adherence. And, in theory, it could be cheaper to manufacture fewer tablets, which would benefit low- and middle-income countries. To date, neither Gilead nor Merck has announced pricing or any plans to partner with companies to produce generic versions of the pill.

The studies enrolled volunteers who were virally suppressed (having no detectable viral load)—607 people in ISLEND-1 and 624 in ISLEND-2—who had been taking antiretroviral therapy. Researchers switched half of the participants in each study to the weekly combination pill and compared the outcomes with the control group (those who continued on their current regimens). One key difference: ISLEND-1 is an ongoing, double-blind trial that enrolled volunteers taking the combination of bictegravir, emtricitabine and tenofovir alafenamide (brand name Biktarvy). In the open-label ISLEND-2 trial, researchers recruited people who were taking a variety of antiretrovirals, which varied depending on the country. For example, in South Africa, where several of the trial sites were located, the local standard of care is dolutegravir, lamivudine or emtricitabine and tenofovir (known as TLD, a combination not available in the U.S.). The designs for the two trials were otherwise similar. The exclusion criteria included a history of virologic failure and hepatitis B infection; the primary endpoint for both studies was the proportion of individuals with a viral load greater than or equal to 50 at week 48. 

Both studies enrolled a diverse population of more than 1,200 people living with HIV, one in sites in Asia, Australia, Europe, the Americas and South Africa. Across the two studies, the median age was 51; 14% were 65 or older. Just over a quarter (27%) were assigned female at birth, 31% identified as Black, 15% identified as Asian and 23% identified as Latinx. 

In the ISLEND-1 study, at week 48, no participant on the weekly regimen had a viral load equal to or greater than 50, compared with one individual (0.3%) who remained on baseline therapy. The percentage of people with low viral loads was similar in both arms: 93% on the weekly pill and 92% on baseline therapy had a viral load of less than 50 (undetectable). 

At week 48 of ISLEND-2, one participant (0.3%) who switched to the weekly regimen had a viral load equal to or greater than 50, compared with four people (1.3%) who continued baseline therapy. 

In both ISLEND studies, the overall rate of adverse events (AEs) was comparable between study arms, and discontinuations due to adverse events were rare, Dr. Colson said. There were some differences in AEs between the studies, however. While treatment-related AEs were very similar in both arms of ISLEND-1, 18% of participants in ISLEND-2 reported treatment-related adverse events with the once-weekly pill compared to less than 1% of people receiving standard of care regimens. The most commonly reported were headache (5%), nausea (3%) and diarrhea (3%), and no more serious treatment-related adverse events were reported. 

There were no clinically significant changes in the CD4 count, total lymphocyte count or body weight through week 48 in either study. Adherence, a big reason for switching to a less-frequent dosing option, was very high in both studies. “This provides reassurance that changing from daily to weekly dosing does not increase the risk of missed doses,” Dr. Colson said.

One big takeaway from both studies was preference: more participants preferred the weekly regimen versus the standard of care daily treatment, and more than 70% said they were more or much more satisfied with the weekly islatravir/lenacapavir combination compared with their previous regimen. 

The ISLEND studies’ findings were summarized in a media statement by Gilead.