An indirect comparison of 144-week efficacy, safety, and tolerability of dolutegravir plus lamivudine and second-generation integrase inhibitor-based, 3-drug, single-tablet regimens in therapy-naive people with HIV-1

• Published in: AIDS research and therapy Vol. 20; no. 1; p. 17
• Main Authors: Evitt, Lee A, Nanji, Sakina, Grove, Richard A, Okoli, Chinyere, van Wyk, Jean, Snedecor, Sonya J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.03.2023; BioMed Central; BMC
• Subjects: Abacavir; Adverse events; Anti-HIV agents; Anti-HIV Agents - adverse effects; Antiretroviral agents; Antiretroviral therapy; Antiviral agents; Bictegravir; Brief Report; Care and treatment; CD4 antigen; Clinical trials; Comparative analysis; Dolutegravir; Dosage and administration; Drug therapy; Durability; Effectiveness; Emtricitabine; Failure analysis; Hepatitis; Heterocyclic Compounds, 3-Ring - adverse effects; Highly active antiretroviral therapy; HIV; HIV (Viruses); HIV infection; HIV Infections - drug therapy; HIV Integrase Inhibitors - therapeutic use; HIV Seropositivity - drug therapy; HIV-1; HIV-1 infection; Human immunodeficiency virus; Humans; Inhibitors; Integrase; Lamivudine; Lamivudine - adverse effects; Literature reviews; Meta-analysis; Patient outcomes; Reverse transcriptase inhibitors; Risk factors; RNA; Safety; Tablets; Teenagers; Tenofovir; United Kingdom; United States > US; Emtricitabine; HIV-1 infection; Antiretroviral agents; Bictegravir; Lamivudine; Tenofovir alafenamide; Dolutegravir
• DOI: 10.1186/s12981-023-00507-1
• ISSN: 1742-6405

The long-term efficacy and safety of the 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) and 3-drug single-tablet regimens recommended for antiretroviral therapy (ART)-naive people with HIV-1 (PWH) have yet to be compared directly in clinical trials. This indirect treatment comparison (ITC) was conducted to compare the durability of efficacy and long-term safety of DTG + 3TC vs second-generation, integrase strand transfer inhibitor (INSTI)-based, 3-drug, single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and DTG/abacavir/3TC (DTG/ABC/3TC) at Week 144 after treatment initiation. A systematic literature review identified 4 trials evaluating the treatment regimens of interest in ART-naive PWH (GEMINI-1, GEMINI-2, GS-US-380-1489, and GS-US-380-1490). Safety, efficacy, and tolerability results were compared using fixed-effects Bucher ITC methodology to calculate relative outcomes. Rates of virologic suppression (HIV-1 RNA < 50 copies/mL, US Food and Drug Administration Snapshot analysis) and virologic failure (HIV-1 RNA ≥ 50 copies/mL) as well as mean change in CD4 + cell count were similar with DTG + 3TC, BIC/FTC/TAF, and DTG/ABC/3TC at Week 144. Serious adverse events occurred less frequently with DTG + 3TC compared with both BIC/FTC/TAF (odds ratio [OR], 0.51; 95% CI 0.29-0.87; P = 0.014) and DTG/ABC/3TC (OR, 0.38; 95% CI 0.19-0.75; P = 0.006). Discontinuations and overall adverse events were similar across all 3 regimens. These results suggest that the 2-drug regimen DTG + 3TC offers comparable and durable efficacy with fewer serious adverse events vs BIC/FTC/TAF and DTG/ABC/3TC through 144 weeks of treatment in ART-naive PWH. These long-term comparative data support the therapeutic value of DTG + 3TC for PWH.