Doravirine and islatravir for HIV-1 treatment: A systematic review and meta-analysis with GRADE assessment

Abstract

Background Two-drug antiretroviral regimens are increasingly explored to simplify HIV-1 treatment while maintaining durable viral suppression. Doravirine combined with Islatravir (DOR/ISL) represents a novel non-integrase strand transfer inhibitor (non-INSTI) regimen. However, comprehensive synthesized evidence remains limited. Objectives To systematically evaluate the efficacy and safety of fixed-dose Doravirine (100 mg) plus Islatravir (0.25 or 0.75 mg) for HIV-1 treatment in adults. Design Systematic Review and Meta-Analysis. Data Sources and Methods Comprehensive searches of PubMed, Embase, Scopus, Cochrane CENTRAL, ICTRP, and ClinicalTrials.gov were performed to identify RCTs evaluating Doravirine/Islatravir for HIV-1 treatment. The primary outcome was viral suppression (HIV-1 RNA <50 copies/mL) at 48 weeks. Secondary outcomes included immunological and safety endpoints. Results Seven RCTs (N = 3,589) were included. In primary analyses restricted to the approved 0.25 mg dose (four RCTs, N = 1,639), DOR/0.25 mg ISL achieved non-inferior viral suppression compared to standard ART at 48 weeks (RR = 1.01, 95% CI: 0.97-1.04, p = 0.63), with consistent efficacy across virologically suppressed and treatment-naïve cohorts. DOR/0.25 mg ISL showed no significant differences versus controls in CD4+ cell count (MD = -6.35 cells/µL, p = 0.51) or total lymphocyte count changes (MD = -0.02 x 109/L, p = 0.54). Statistically significant declines in CD4+ and lymphocyte counts were strictly restricted to the discontinued 0.75 mg dose. Overall adverse events and treatment discontinuations due to adverse events were comparable between groups. Conclusion DOR/ISL provides non-inferior virologic efficacy compared with standard antiretroviral therapy with a favorable safety profile. The 0.25 mg Islatravir dose maintains antiviral efficacy while avoiding the immunologic declines observed with 0.75 mg dose, supporting its suitability as a simplified two-drug regimen. Registration This review protocol was prospectively registered with PROSPERO (CRD420261321479).