Adverse Drug Reactions Among Patients Initiating Second-Line Antiretroviral Therapy in South Africa

Introduction: Understanding the occurrence of antiretroviral (ARV)-related adverse events (AEs) among patients receiving second-line antiretroviral therapy (ART) is important in preventing switches to more limited and expensive third-line regimens. Objective: This study aimed to estimate the rates and examine predictors of AEs among adult HIV-1-infected patients receiving second-line ART in the Right to Care (RTC) clinical cohort in South Africa. Methods: This was a cohort study of HIV-1-infected adult patients (≥ 18 years of age) initiating standard second-line ART in South Africa from 1 April 2004 to 10 January 2016. Our primary outcome was the development of an AE within 24 months of initiating second-line therapy. We used Kaplan–Meier survival analysis to determine AE incidence in the first 24 months of second-line ART. Predictors of AEs were modelled using a Cox proportional hazards model. Results: A total of 7708 patients initiated second-line ART, with 44.5% developing at least one AE over the first 24 months of second-line treatment. The highest AE incidence was observed among patients receiving abacavir (ABC) + lamivudine (3TC) + ritonavir-boosted lopinavir/atazanavir (LPVr/ATVr) (52.7/100 person-years (PYs), 95% confidence interval (CI): 42.9–64.8), while patients initiated on a tenofovir (TDF) + emtricitabine (FTC)/3TC + LPVr regimen had the lowest rate of AEs (26.4/100 PYs, 95% CI: 24.9–28.3). Clinical predictors of AEs included experiencing AEs when receiving first-line ART (adjusted hazard ratio (aHR) 2.3, 95% CI: 1.9–2.8), lower CD4 cell count (0–199 vs. ≥ 350 cells/mm 3 ; aHR 1.4, 95% CI: 1.4–1.8), and switching to second-line therapy from an ABC-base first-line regimen (ABC + 3TC + efavirenz/nevirapine [EFV/NVP] vs. TDF + 3TC/FTC + EFV/NVP; aHR 3.4, 95% CI: 1.1–11.1). Conclusions: The rates of AEs were lowest among patients receiving a TDF-based second-line regimen. Patients with poorer health at the time of switch were at higher risk of AEs when receiving second-line ART and may require closer monitoring to improve the durability of second-line therapy.