Background: Obesity is increasing worldwide including in people living with HIV (PLWH). Antiretroviral pharmacokinetic data in obesity are limited.Objectives: To measure antiretroviral drug concentrations in obese and nonobese PLWH treated with the fixed-dose combination of efavirenz-tenofovir-emtricitabine. To determine pharmacokinetic differences across indicators of obesity and their associated immunovirological outcomes. Methods:We conducted a cross-sectional sample analysis of 2 cohort studies. We measured mid-dose efavirenz, 8-hydroxy-efavirenz, tenofovir, and emtricitabine concentrations. Antiretroviral drug concentrations were analyzed by body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Results:We performed a study of 213 participants: General obesity was detected in 20.4% using BMI and abdominal obesity in 53.6% using WC and 62.4% using WHR, respectively. The median concentrations of all antiretroviral drugs were lower among obese participants determined by BMI and WC, with efavirenz showing greater differences than tenofovir or emtricitabine. For BMI, results were most striking for efavirenz (1752.3 vs 2342.9 ng/mL, P = 0.002) with lower concentrations in obese participants. Using WC, efavirenz (1845.8 vs 2571.2 ng/mL, P , 0.001), tenofovir (65.8 vs 73.2 ng/mL, P = 0.036), and emtricitabine (159.5 vs 221.0 ng/mL, P = 0.005) concentrations were lower in obese participants. Eight-hydroxyefavirenz concentrations were similar in nonobese and obese participants for WC. Using WHR, the concentrations of all antiretroviral drugs were lower in the obese population, most strikingly for emtricitabine (173.5 vs 229.0 ng/mL, P = 0.015). There were no immunovirological associations. Conclusion:We found lower antiretroviral concentrations in all obese groups, most strikingly in participants with abdominal obesity determined by WC. Lower drug concentrations had no immunovirological associations.