Within 24 months of starting second-line therapy at a large HIV clinical cohort in South Africa, close to half of the patients (3429/7708, 44.5%) had experienced at least one second-line antiretroviral therapy-related adverse event (AE).

Rates of AEs among patients receiving second-line regimens such as TDF + FTC/3TC + LPVr are lower than that of patients receiving other regimens (3TC + ABC + LPVr/ATVr; AZT + ddI + LPVr; AZT + 3TC + LPVr/ATVr).

In resource-limited settings such as South Africa, where access to third-line therapy is not guaranteed, the early detection and effective management of AEs, including low-grade AEs, could improve patient outcomes in second-line therapy.