The INSIGHT START study, a large international randomized trial, evaluated the benefits and risks of initiating antiretroviral therapy (ART) in HIV-positive adults with a CD4+ count above 500 cells per cubic millimeter. Patients were randomly assigned to either immediate ART initiation or deferred ART initiation until the CD4+ count dropped to 350 cells per cubic millimeter or they developed AIDS or another condition requiring ART. The primary endpoint was a composite of serious AIDS-related events, serious non-AIDS-related events, and death. After an interim analysis, the study's data and safety monitoring board recommended offering ART to patients in the deferred group. The results showed that immediate ART initiation significantly reduced the primary endpoint (hazard ratio 0.43, 95% CI 0.30 to 0.62; P<0.001) and both serious AIDS-related (hazard ratio 0.28, 95% CI 0.15 to 0.50; P<0.001) and serious non-AIDS-related events (hazard ratio 0.61, 95% CI 0.38 to 0.97; P = 0.04). The benefits were consistent across subgroups, and there was no increased risk of adverse effects. The findings suggest that immediate ART initiation in this patient population provides net benefits over deferring it.The INSIGHT START study, a large international randomized trial, evaluated the benefits and risks of initiating antiretroviral therapy (ART) in HIV-positive adults with a CD4+ count above 500 cells per cubic millimeter. Patients were randomly assigned to either immediate ART initiation or deferred ART initiation until the CD4+ count dropped to 350 cells per cubic millimeter or they developed AIDS or another condition requiring ART. The primary endpoint was a composite of serious AIDS-related events, serious non-AIDS-related events, and death. After an interim analysis, the study's data and safety monitoring board recommended offering ART to patients in the deferred group. The results showed that immediate ART initiation significantly reduced the primary endpoint (hazard ratio 0.43, 95% CI 0.30 to 0.62; P<0.001) and both serious AIDS-related (hazard ratio 0.28, 95% CI 0.15 to 0.50; P<0.001) and serious non-AIDS-related events (hazard ratio 0.61, 95% CI 0.38 to 0.97; P = 0.04). The benefits were consistent across subgroups, and there was no increased risk of adverse effects. The findings suggest that immediate ART initiation in this patient population provides net benefits over deferring it.