OBJECTIVES: The long-term efficacy of commonly used core agents used to treat antiretroviral therapy (ART) naive patients with human immunodeficiency virus, type 1 (HIV-1), infection in real world settings is poorly understood. We compared rates of virologic failure (VF) following core agent initiation among patients initiating on dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL) and darunavir (DRV).

METHODS: ART-naive, HIV-1 patients initiating DTG, EVG, RAL, or DRV between 12Aug2013 and 31July2017 were selected from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. VF was defined as (i) 2 consecutive HIV viral load (VL) ≥200 copies/mL after 36 weeks of ART, or (ii) 1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks, or (iii) 2 consecutive VL ≥200 copies/mL after suppression (VL ≤50 copies/mL) before 36 weeks, or (iv) 1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Survival analyses were conducted with Kaplan Meier methods and multivariate Cox Proportional Hazards modeling.

RESULTS: There were 6,233 ART-naive patients who initiated DTG (35.9%), EVG (48.3%), DRV (13.1%) or RAL (2.6%). Median follow-up time was 19.4 months (IQR: 12.8-30.0). Compared to DTG, EVG users were more likely to be African American, from the southern U.S. with lower baseline VL; DRV and RAL users were older, less likely to be male or Hispanic, more likely to be African American, from the southern US with lower baseline CD4 cell counts and higher baseline VL and comorbidity. VF was experienced by 9.2% DTG, 11.4% EVG, 19.0% DRV and 23.1% RAL users. Compared to DTG, the adjusted hazard ratio for VF was 1.23 (95% CI: 1.02, 1.50) for EVG, 2.61 (2.09, 3.27) for DRV, and 3.44 (2.34, 5.05) for RAL.

CONCLUSIONS: DTG users were less likely to experience VF compared to EVG, RAL and DRV initiators.