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Although more than one in two HIV-infected persons may develop central fat accumulation soon after commencing antiretroviral therapy, the association between antiretroviral therapy and body fat changes has not been consistent across primary epidemiological studies. We conducted a systematic review with meta-analyses to estimate the pooled effects of antiretroviral therapy on different measures of body fat, and to examine factors that potentially modify these effects. We searched for studies that compared body mass index, waist circumference, combined overweight/obesity, and central obesity between HIV-infected adults naive and exposed to antiretroviral therapy. Random-effects subgroup and meta-regression analyses were performed to identify potential effect-modifiers of the pooled associations. Sixty studies, comprising data on 53,199 HIV-infected participants, were eligible for the meta-analyses. Antiretroviral therapy was associated with increased body mass index (SMD: 0.17 kg/m2; 95% CI: 0.07-0.26), waist circumference (SMD: 0.20 cm; 95% CI: 0.07-0.33), overweight/obesity (borderline significance: OR: 1.36; 95% CI: 0.99-1.86), and abdominal obesity (OR: 1.49; 95% CI: 1.16-1.90). In addition, antiretroviral therapy was associated with significant increases in body mass index, overweight/obesity, and central obesity among patients with CD4 counts < 350 cells/mm3, but not among patients with higher CD4 counts (Pinteraction < 0.05 for all). Overall, exposure to antiretroviral therapy was associated with increased risks of generalized and central obesity, and risks may be exacerbated by lower CD4 counts. These findings suggest that weight management and obesity prevention programs may be worth considering as part of routine HIV care.