Weekly islatravir plus lenacapavir maintains HIV virologic suppression

1. In this randomized controlled trial, once-weekly oral islatravir (ISL) plus lenacapavir (LEN) maintained high rates of HIV-1 virologic suppression through 48 weeks, comparable to daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV-1.

2. Adverse event rates were similar between groups, and once-weekly ISL plus LEN was not associated with any treatment-related serious adverse events.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Daily antiretroviral therapy is the standard treatment for HIV-1, but maintaining optimal adherence remains challenging due to factors such as stigma, pill fatigue, and other personal or social barriers. Longer-acting therapies, including islatravir (ISL) and lenacapavir (LEN) may improve adherence and clinical outcomes by reducing dosing frequency. This study evaluated the efficacy and safety of once-weekly oral ISL plus LEN compared with daily bictegravir, emtricitabine, and tenofovir alafenamide combination (B/F/TAF) in virologically suppressed people with HIV over 48 weeks. Both treatment regimens maintained viral suppression throughout the study period, and adherence was high in both groups, indicating that a once-weekly regimen could be a feasible alternative to daily therapy. Adverse events were reported in both groups, with most being mild or moderate, and serious adverse events were uncommon. While the findings suggest that ISL plus LEN is non-inferior to daily antiretroviral therapy in maintaining virologic suppression and appears generally safe, the study’s generalizability is limited by its open-label design, modest sample size, and US-based population. Overall, these results support the potential of once-weekly ISL plus LEN as a convenient and effective alternative to daily therapy, highlighting the need for larger, multicenter studies to confirm safety, adherence, and long-term efficacy across diverse populations.

Click to read this study in AIM

Relevant Reading: Single doses as low as 0.5 mg of the novel NRTTI MK-8591 suppress HIV for at least 7 days

In-Depth [randomized controlled trial]: This randomized controlled trial evaluated the safety and efficacy of once-weekly islatravir (ISL) plus lenacapavir (LEN) compared with daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed people with HIV (PWH). Participants were enrolled at 44 U.S. centers, aged 18 years or older, with HIV-1 RNA <50 copies/mL for at least 24 weeks, CD4+ T-cell count ≥0.35 x 10⁹ cells/L, and lymphocyte count ≥0.9 x 10⁹ cells/L. Exclusion criteria included prior virologic failure, active hepatitis B infection, resistance mutations, or significant ECG abnormalities. A total of 104 participants were randomized equally to ISL + LEN or B/F/TAF. Mean age was 44 years, 18.3% were assigned female at birth, and 50% were non-White. Baseline CD4+ T-cell count averaged 0.786 x 10⁹ cells/L. At week 24, 1 participant in the ISL + LEN group and none in the B/F/TAF group had HIV-1 RNA ≥50 copies/mL; viral load in that participant was resuppressed by week 36. Overall, 94.2% of participants in both groups maintained viral suppression at week 24. By week 48, no participants had HIV-1 RNA ≥50 copies/mL, with suppression maintained in 94.2% of ISL + LEN recipients and 92.3% of B/F/TAF recipients. Adverse events (AEs) occurred in 80.8% of ISL + LEN participants and 76.9% of B/F/TAF participants, with the most common being upper respiratory tract infection, COVID-19, and diarrhea. Grade 3 or 4 AEs occurred in 7.7% versus 1.9%, and serious AEs in 5.8% versus 0%, none considered treatment-related. Treatment-related AEs were reported in 19.2% of ISL + LEN participants and 5.8% of B/F/TAF participants, all mild or moderate. Median adherence was 100% for ISL + LEN and 98.8% for B/F/TAF. CD4+ T-cell counts remained stable in both groups. Overall, once-weekly ISL + LEN maintained high rates of virologic suppression through 48 weeks without increasing serious AEs, suggesting it may be a safe and effective alternative to daily therapy.

Image: PD

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