P-369. Safety and Efficacy of Doravirine/Islatravir (DOR/ISL) 100/0.25 mg Once Daily (QD) after ISL Dose Reduction from 0.75 mg: Week 48 Results from an Open-Label Phase 3 Study

Abstract Background Phase 2 and Phase 3 studies of DOR/ISL 100/0.75 mg QD demonstrated good antiretroviral activity in adults with HIV-1. However, declines in total lymphocyte and/or CD4+ T-cell counts were observed. Modeling studies predicted that ISL 0.25 mg would achieve efficacy comparable to ISL 0.75 mg with no meaningful declines in total lymphocyte or CD4+ T-cell counts. We studied the safety and efficacy of DOR/ISL 100/0.25 mg in participants who had received DOR/ISL 100/0.75 mg previously.Table 1.Summary of Adverse Events through Week 48Table 2.Virologic Outcomes at Week 48 (FDA Snapshot Approach; Full Analysis Set*) Methods In this phase 3, open-label, single-arm study (NCT05766501), adults with HIV-1 RNA < 200 copies/mL who had tolerated DOR/ISL 100/0.75 mg QD in a previous study (MK8591A-018, 020, or 033) switched to open-label DOR/ISL 100/0.25 mg QD for maintenance therapy. The primary objective was to evaluate the safety and tolerability of DOR/ISL 100/0.25 mg QD through week 96. Secondary objectives included assessment of the antiretroviral activity of DOR/ISL (FDA Snapshot Approach) and changes in total lymphocyte and CD4+ T-cell counts. An interim analysis conducted at week 48 is reported here.Figure 1.Total Lymphocyte Count, Mean Change from Baseline (and 95% CI)Figure 2.CD4+ T-cell Count, Mean Change from Baseline (and 95% CI) Results 639 participants entered the study: mean age 44.7 (range 20-79) years, 69.3% male, 55.7% white, and 31.5% black/African American. Mean time on DOR/ISL before enrollment was 31.7 (range 17.6-61.9) months. By week 48, adverse events (AE) were reported by 75.4% of participants and were considered drug-related in only 2.2% (Table 1). Serious AEs were reported in 5.6% of participants; none were drug-related. Three participants (0.5%) discontinued treatment due to an AE; none were drug-related. At week 48, HIV-1 RNA was < 50 copies/mL in 598 participants (93.6%) and ≥50 copies/mL in 11 (1.7%) (Table 2). Two participants (0.3%) developed clinically significant viremia (confirmed HIV-1 RNA ≥200 copies/mL); resistance data were not available due to assay failure. Total lymphocyte and CD4+ T-cell counts showed mean increases from baseline of 0.19x109 cells/L (95% CI: 0.15, 0.22) and 74.5 cells/mm3 (95% CI: 59.2, 89.8), respectively, at week 48 (Figures 1 and 2). Conclusion DOR/ISL 100/0.25 mg QD was generally well tolerated and maintained virologic suppression in a high proportion of participants who had previously received DOR/ISL 100/0.75 mg. Baseline total lymphocyte and CD4+ T-cell counts increased after ISL dose reduction. Disclosures Cheryl McDonald, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Merck: Grant/Research Support|Viiv: Grant/Research Support Mark Bloch, MBBS, MMed, Gilead Sciences: Lectures|GSK: Board Member|GSK: Lectures|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Lectures, Support to attend scientific meetings Christopher Bettacchi, MD, Merck: Honoraria|Viiv: Honoraria Margaret Johnson, MD, Merck & Co., Inc.: Grant/Research Support Euna Kim, BA, Merck & Co., Inc.: Stocks/Bonds (Public Company) Uche Nwoke, MS, Merck & Co., Inc.: Stocks/Bonds (Public Company) Michelle C. Fox, MD, Merck & Co., Inc.: Employment|Merck & Co., Inc.: Stocks/Bonds (Public Company) Luisa M. Stamm, MD, PhD, Merck & Co., Inc.: Employment|Merck & Co., Inc.: Stocks/Bonds (Public Company) Mengchun Li, MD, Merck & Co., Inc.: Stocks/Bonds (Public Company) Wayne Greaves, MD, Merck & Co., Inc.: Stocks/Bonds (Public Company)