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DENVER -- A once-weekly oral antiretroviral therapy (ART) regimen of the investigational drug islatravir, a nucleoside reverse transcriptase translocation inhibitor, with lenacapavir (Sunlenca) showed similar efficacy to daily oral ART in people with HIV, a phase II randomized study showed.

The virologic suppression rate was 94.2% in both the patients who received the weekly regimen and those who received the daily regimen of bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy) at week 24, reported Amy Colson, MD, MPH, of the Community Resource Initiative in Charlestown, Massachusetts, at the Conference on Retroviruses and Opportunistic Infections.

"Once-weekly oral antiretrovirals have the potential to address pill fatigue and adherence challenges related to daily oral treatment for HIV-1 infection," Colson told attendees. "Both islatravir and lenacapavir have multiple mechanisms of action, potent antiretroviral activity at low doses, and long half-lives that allow for weekly dosing."

Graeme Meintjes, MBChB, of the University of Cape Town in South Africa, who was not involved in the study, said it presented "an exciting option for people with adherence problems," though it was small and needs the efficacy and safety confirmed in a much larger study. "It's not necessarily going to solve [adherence challenges] because some people might struggle with the once-weekly dose, but it just provides another option for people."

Although people with HIV in many parts of the world have the option of monthly injectable ART instead of daily oral ART, many patients may feel more comfortable sticking with an oral medication or have problems with injection site reactions.

"We see all the data on the acceptability and preference towards an injection, but that doesn't mean everybody will go for that option," Meintjes said. In addition, injectable ART is unaffordable or otherwise unavailable in many parts of the world, including South Africa.

The open-label study enrolled 104 adults who had a viral load of less than 50 c/mL while on bictegravir/emtricitabine/tenofovir alafenamide, no history of virologic failure, a CD4 count of at least 350 cells/µL, no hepatitis B infection, and at least 900 cells/µL of lymphocytes.

The participants, who had a median age of 40, included one transgender female and one non-binary participant, and 18.3% of participants were female at birth. Half the participants were white, 35.6% were Black, and the others were of different races; 28.8% were Hispanic. Participants' mean CD4 count at baseline was 786 cells/µL, and 92.3% had at least 500 cells/µL.

The 52 participants in the intervention arm received a once-weekly dose of 2-mg islatravir with 300-mg lenacapavir, while the 52 control participants received one-daily bictegravir/emtricitabine/tenofovir alafenamide. In an extension phase, all enrollees received the investigational islatravir-lenacapavir once-weekly combination.

The primary endpoint was the proportion of participants with HIV RNA of at least 50 c/mL at week 24. Secondary endpoints included the proportion of participants with HIV RNA of at least 50 c/mL at weeks 12 and 48; the proportion with less than 50 c/mL at weeks 12, 24, and 48; the change in CD4 from day 1; adverse events leading to discontinuation; and pharmacokinetics parameters.

No significant differences in CD4 count or absolute lymphocyte count occurred between the groups at week 24, and no participants discontinued treatment due to decreases in CD4 or absolute lymphocyte count.

Adverse events of any kind occurred in 76.9% of islatravir-lenacapavir participants and 73.1% of daily ART participants, and treatment-related adverse events occurred in 17.3% and 5.8%, respectively. No serious treatment-related adverse events occurred in either group. Two participants receiving islatravir-lenacapavir discontinued treatment due to adverse events, but neither were treatment-related.

Grade 3 lab abnormalities occurred in 9.6% of islatravir-lenacapavir participants and 7.8% of daily ART participants, and one islatravir-lenacapavir participant had a grade 4 lab abnormality of increased creatine kinase. However, none of the grade 3 or 4 laboratory abnormalities were determined to be clinically significant, except the alanine transaminase elevation that occurred in one patient with acute hepatitis B that developed during the trial.

One participant had an HIV RNA count of 64 c/mL at week 24 but it had dropped below 50 c/mL at week 30 without a change in regimen, and the participant remains on the study drug with no detected emergent resistance.

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