Phase 3 trials show promising results for once-weekly islatravir-lenacapavir pill for HIV treatment | AIDS 2026

Prospects for a weekly pill for HIV treatment are looking bright after findings from two phase 3 trials were presented today at AIDS 2026, the 26th International AID Conference, in Rio de Janeiro, in Brazil.

The weekly pill is a combination of islatravir, a nucleoside reverse transcriptase translocation inhibitor developed by Merck, and lenacapavir, a capsid inhibitor developed by Gilead Sciences, that has become well-known as an effective preventive agent in its long-acting injectable form.

Results from the two trials, named ISLEND-1 and ISLEND-2, were shared at a press conference last week, but researchers presented them formally today at the AIDS 2026 conference, which is sponsored by the International AIDS Society.

The ISLEND-1 results were presented this afternoon by Jürgen Rockstroh, M.D., a professor of medicine and head of the HIV Outpatient Clinic at the University Hospital Bonn in Germany, and published simultaneously in the New England Journal of Medicine. The ISLEND-2 results were presented this morning by Amy E. Colson, M.D., M.P.H., research director at the Community Resource Initiative, a nonprofit research and patient assistance organization in Boston.

Currently, people living with HIV face a lifetime of treatment with antiretroviral medications to hold the infection in check. As a result, a major thrust of contemporary HIV research is developing treatment formulations that are easier to stick with and need to be administered less often than the daily oral pills that are the predominant form of treatment around the world.

“Oral weekly antivirals have the potential to address pill fatigue and adherence challenges related to daily oral treatment for HIV-1,” Rockstroh said at the beginning of his presentation.

Results presented by Rockstroh and Colson today showed that at the halfway point of the two 96-week trials, the islatravir-lenacapavir pill is noninferior to daily treatment pills as far as controlling the HIV virus as measured by the number of study participants who developed an HIV-1 RNA level of 50 copies per milliliter (mL) or more. The data that Rockstroh shared showed no study participants among the 304 randomly selected to be treated with islatravir-lenacapavir developed that viral load compared with one who did in the comparison group of 303 study participants that continued to take an oral HIV treatment drug that contains three antiretrovirals: bictegravir, emtricitabine and tenofovir alafenamide. That combination pill is sold under the brand name Biktarvy in the United States.

The data shared by Colson showed one study participant among the 314 in the islatravir-lenacapavir group developed an HIV-1 RNA level of 50 copies or more compared with four among the 312 in the comparison group that stuck with daily treatment pills. In ISLEND-2, patients in the comparison group and their clinicians were allowed to decide which daily treatment to use so long as it fell into the standard of care.

The data that Rockstroh and Colson shared also allayed some concerns raised by other trials involving islatravir that the drug would substantially decrease CD4+ T cells and lymphocytes. The data shared by Colson showed a steeper decline in the CD4+ T cell levels in the islatravir-lenacapavir group, but at week 48 the levels were the same in the islatravir-lenacapavir group and the comparison group. Rockstroh’s data showed only a minor difference in the drops in the CD4+ T cell counts between the islatravir-lenacapavir group and the patients who continued to be treated with Biktarvy. In both studies, no study participants discontinued treatment because of decreased CD4+ T cell counts.

Tenofovir alafenamide is used to treat hepatitis B, so one concern about islatravir-lenacapavir is that patients might develop hepatitis B, particularly if they are not vaccinated. Rockstroh reported that one person who was not vaccinated developed hepatitis B and discontinued treatment. Colson said two people discontinued treatment in the ISLEND-2 trial, one because of an acute hepatitis B infection and the other because of elevated bilirubin, which can be a sign of hepatitis B infection.

Double-blinded vs. open-label

The basic design of the two trials is similar, with half of the study participants in each study switching from oral treatment to the weekly islatravir-lenacapavir pill that contains two milligrams (mg) of islatravir and 300 mg of lenacapavir and the other half sticking with the daily pills. Both studies are scheduled to last 96 weeks, so today’s data is a snapshot at their midway points. Aside from a difference in the daily pills (Biktarvy in ISLEND-1 and choice among standards of care in ISLEND-2), an important difference between the two trials is that ISLEND-1 is a double-blinded study, whereas ISLEND-2 is open-label. That difference may explain some differences in how the adverse event tallied up in the two trials. In ISLEND-1, the number of treatment-related events of any kind was basically the same (41 in the islatravir-lenacapavir group compared with 40 in the Biktarvy group). In ISLEND-2, there was a large difference (58 in the islatravir-lenacapavir group compared with one in the daily pill group). Colson noted that such discrepancies are a pattern seen in open-label studies that involve study patients that switch from established treatment to an experimental one. Colson noted that all the treatment-related adverse events were grade one or two. When the analysis was limited to adverse events grade 3 or higher, neither group had treatment-related adverse events.

Access in low- and middle-income countries

One of the emerging themes of the meeting in Rio is that global response to HIV is now limited by political and economic factors as opposed to scientific ones. The positive result for weekly islatravir-lenacapavir raises questions about what the price and access to the combination will be like after what now seems like near-certain approval by the FDA and other drug regulators and the combination coming on the market. During the question-and-answer period, when Rockstroh was asked about the “access plan” for the combination in low- and moderate-income countries, he said that question would need to be directed to company representatives, and there was an awkward silence when the moderator of the session asked if there were any company representatives present who wanted to respond.

Last week, a spokesman for Gilead shared a written statement with Managed Healthcare Executive that said it was “too early” to say what the price of the islatravir-lenacapavir pill might be. “Our decades of experience collaborating with a range of stakeholders will help us explore pathways with the goal of facilitating rapid uptake and broad access around the world,” the statement said, referring to both Merck and Gilead.

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