577. Week 48 Results of a Phase 2 Study Evaluating Once-weekly Oral Islatravir Plus Lenacapavir

作者：Amy E. Colson, Gordon E Crofoot, Peter Ruane, Moti Ramgopal, Alexandra W. Dretler, Ronald Nahass, Gary Sinclair, Mezgebe Berhe, F. Shihadeh, Shanyu Liu, Stephanie O. Klopfer, Sharline Madera, Hadas Dvory‐Sobol, Martin S. Rhee, Elizabeth G. Rhee, Jared M. Baeten, Joseph J. Eron · 发表于：Open Forum Infectious Diseases · 年份：2025 · DOI：10.1093/ofid/ofae631.015 · 被引用次数：6 · 研究领域：HIV/AIDS drug development and treatment、Pharmacological Effects and Toxicity Studies、HIV-related health complications and treatments

Abstract Background Both islatravir (ISL), a nucleotide reverse transcriptase translocation inhibitor, and lenacapavir (LEN), a capsid inhibitor, have potent anti-HIV-1 activity and pharmacokinetic profiles permitting once-weekly oral dosing. Week (W) 24 data (primary endpoint) from the current Phase 2 study were previously reported (CROI 2024); weekly oral ISL 2 mg + LEN 300 mg maintained high rates of viral suppression (HIV-1 RNA < 50 copies/mL) with no clinically relevant decreases in CD4+ T-cells or lymphocytes, which had been previously observed with higher ISL doses. Here, we report W48 results.Table:Week 48 Virologic Outcome Data by FDA Snapshot AlgorithmaAEs leading to study discontinuation included large intestine perforation and renal colic (n=1); and hepatitis B (n=1).bLast available on-treatment HIV-1 RNA <50 copies/mL.AE, adverse event; B/F/TAF, bictegravir/emtricitabine/tenofovir alafenamide; FDA, Food and Drug Administration; ISL, islatravir; LEN, lenacapavir; W, week. Methods In this Phase 2, randomized, open-label, active-controlled study (NCT05052996), virologically suppressed adults on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) were randomized 1:1 to receive weekly oral ISL 2 mg + LEN 300 mg or to continue daily B/F/TAF. Virologic outcomes (using FDA-defined snapshot algorithm), adverse events (AEs), CD4+ T-cells, and lymphocytes were assessed. Results Overall, 104 participants were randomized and dosed; median age (range) was 4...