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To determine the incidence of antiretroviral therapy (ART) adherence among treatment-naive HIV-infected patients and to evaluate the impact of single-tablet regimen (STR) on ART adherence among this population.Retrospective cohort study.We used a nationally representative sample of IQVIA LRx Lifelink individual level pharmacy claims database during 2011–2016, and defined adult patients with index date (first complete ART regimen prescription fill date) after 30 June 2011 as treatment naïve. We estimated ART adherence, measured as the proportion of days covered during 1 year following the index date. We conducted multivariable analysis to identify the factors associated with optimum adherence (≥90% proportion of days covered). We also compared adherence between patients prescribed STR and multiple-tablet regimens among those prescribed integrase strand transfer inhibitor-based or nonnucleoside reverse transcriptase inhibitor-based regimens.Overall 42.9% of the patients were optimally adherent. Adherence was significantly lower among blacks, Hispanics and patients in low-income communities. Adjusting for the covariates, patients on STR had higher incidence of optimum adherence compared with those on multiple-tablet regimens among patients on integrase strand transfer inhibitor-based regimens [49 vs. 24%, relative risk, 2.16 (95% confidence interval: 1.96–2.26)], but no significant difference was observed among those on nonnucleoside reverse transcriptase inhibitor-based regimen [45 vs. 45%, relative risk, 1.12 (95% confidence interval: 0.99–1.26)].Low ART adherence observed among treatment-naive patients in this nationally representative study suggests the need for public health interventions to improve adherence among this population.