Background: Obesity has a large prevalence among HIV-infected patients. Increased adipose tissue mass affects the pharmacokinetics of numerous drugs, but only a few data are available for antiretroviral drugs. Objective: In this study, we aimed to explore the pharmacokinetics of antiretroviral drugs and the immune-virological response in obese patients with HIV infection. Patients and methods: We examined data from 2009 to 2012 in our hospital’s database for HIV-1-infected patients who received an antiretroviral drug among abacavir, emtricitabine, lamivudine, tenofovir, efavirenz, etravirine, nevirapine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir and raltegravir. Obese patients were defined with body mass index (BMI) ≥30 kg/m2 and normal-weight patients with BMI 19–25 kg/m2. Plasma concentrations (C12/24h) were compared for each antiretroviral using Mann-Whitney test. Suboptimal dosing and virological outcome were assessed by logistic regression, adjusting on covariates. Results: We enrolled 291 obese and 196 normal-weight patients. Among the 12 analyzed antiretroviral drugs, tenofovir, efavirenz and lopinavir C12h were significantly lower in obese than normal-weight patients: 66 versus 86 ng/mL, 1,498 versus 2,034 ng/mL and 4,595 versus 6,420 ng/mL respectively (P < 0.001). Antiretroviral C12/24h were more frequently below efficacy thresholds for obese than normal-weight patients after adjustment for other covariates (P < 0.001). Although obese patients showed higher CD4 count than normal-weight (510 vs 444 cells/µL, P < 0.001), the groups did not differ in virological failure rate. Conclusion: This study highlights the impact of obesity on antiretroviral plasma exposure, but identifies no consequence of this suboptimal exposure on the immuno-virological control in this population.