Growth hormone (GH)/insulin-like growth factor (IGF)-1 axis abnormalities have been associated with body composition changes among HIV-infected persons with wasting or lipodystrophy. Little is known of GH/IGF-1 axis alterations with antiretroviral therapy (ART) initiation or differing ART therapies. The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized clinical trial of ART initiation with emtricitabine/tenofovir + efavirenz (FTC/TDF+EFV) versus lamivudine/zidovudine + efavirenz (3TC/ZDV+EFV) in HIV-1-infected individuals from resource-diverse settings. IGF-1 was measured from baseline, week 48, and week 96 stored serum samples. Multivariate models were constructed. 415 participants were included: 170 (41%) were randomized to FTC/TDF+EFV and 245 (59%) to 3TC/ZDV+EFV. The mean age was 35 years, 60% were black, 42% women. The mean IGF-1 level did not change significantly from baseline to week 96 (-0.65 ng/ml; 95% confidence interval (CI)-5.18-3.87), p = .78 and there were no differences by treatment arm at week 96, p = .74. Lower baseline IGF-1 was associated with age, non-white race, greater waist-hip ratio (WHR), low CD4 count, and lower baseline albumin (all p < .01) but not plasma HIV-1 RNA, body mass index, or treatment arm. Greater change in IGF-1 from baseline to 96 weeks was associated with female sex, smaller WHR change, lower baseline albumin, and higher baseline HIV-1 RNA (all p < .01). ART initiation with either ZDV or TDF did not significantly impact overall IGF-1 levels. Baseline and on-Treatment changes in IGF-1 with ART initiation may be related to the body composition changes that occur after ART initiation.