Efficacy and safety of doravirine/islatravir for the treatment of HIV-1: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment.

PURPOSE: Two-drug antiretroviral regimens are being investigated as alternatives to standard three-drug therapy for HIV-1. Doravirine/islatravir is a once-daily oral combination with promising efficacy and safety, but its overall clinical performance has not been systematically quantified. This study evaluated the efficacy and safety of doravirine/islatravir compared with standard triple option therapy in adults living with HIV-1.

METHODS

PubMed, Scopus, Web of Science, and the Cochrane Library were systematically searched for phase III randomized controlled trials comparing doravirine/islatravir with standard triple option therapy. Eligible studies were independently screened, and data were extracted and pooled using R software.

RESULTS

Six phase III trials involving 3,518 adults were included. At 48 weeks, doravirine/islatravir was associated with a significantly lower risk of virological failure (HIV-1 RNA ≥ 50 copies/mL) compared with standard triple option therapy (RR: 0.51, 95% CI [0.30-0.88]; P = 0.015). Rates of virological suppression (< 50 and < 200 copies/mL) were comparable between groups. No significant differences were observed in overall, serious, or grade 3-4 adverse events, or treatment discontinuation due to adverse events. Dose-stratified analyses showed that the 100/0.75 mg formulation was associated with significant declines in CD4 cell count and total lymphocyte count at 48 weeks, whereas the optimized 100/0.25 mg dose showed no significant immunological differences compared with standard triple option therapy.

CONCLUSIONS

Doravirine/islatravir is an effective and generally well-tolerated two-drug regimen for HIV-1. The optimized 100/0.25 mg formulation maintained virological efficacy without significant short-term immunological differences versus standard triple option therapy; however, longer follow-up is needed to confirm its long-term immunological safety.