Abstract
INTRODUCTION: Dolutegravir (DTG) + lamivudine (3TC) demonstrated high rates of virologic suppression (VS) and low rates of virologic failure (VF), discontinuation, and drug resistance in randomized trials. Real-world evidence can support treatment effectiveness, safety, and tolerability in clinical practice and aid in treatment decisions. METHODS: A systematic literature review (SLR) was conducted to identify studies using DTG + 3TC (January 2013-March 2024). Studies were screened to include observational studies reporting 48- or 96-week on-treatment VS, VF, or discontinuation outcomes; proportions of individuals with each outcome at each time point were estimated using random- and common-effects models. RESULTS: Of 249 SLR-identified publications, 43 reported consistently defined outcomes of interest at comparable time points, representing 1480 individuals naive to antiretroviral therapy (ART) and 12,234 individuals with prior ART experience. At weeks 48 and 96, respectively, estimated proportions (95% CIs; random-effects model) with on-treatment VS were high (naive to ART, 0.964 [0.945-0.979] and 0.902 [0.816-0.966]; prior ART, 0.966 [0.950-0.980] and 0.971 [0.946-0.990]), with low estimated proportions experiencing VF (naive to ART, 0.001 [0.000-0.013] and 0.001 [0.000-0.008]; prior ART, 0.009 [0.005-0.015] and 0.015 [0.007-0.024]) and discontinuations for any reason (naive to ART, 0.052 [0.019-0.097] and 0.130 [0.084-0.183]; prior ART, 0.067 [0.042-0.098] and 0.084 [0.047-0.130]). Across identified studies (> 44,000 unique individuals), those reporting resistance outcomes at VF/blip (regardless of emergence) detected integrase strand transfer inhibitor (INSTI) mutations in 0 of 2346 individuals naive to ART and 0.02% (4/20,060) of individuals with prior ART experience (S147G, R263K, G118R + E138K, T66A + G118R + E138K); additionally, N155H was reported in an individual using DTG + 3TC with unknown baseline ART status. CONCLUSION: Overall treatment outcomes in real-world settings confirm the efficacy, tolerability, and high barrier to resistance seen in phase 3 trials across diverse populations, including those naive to ART or with prior ART experience.