Durability of second-line anti-retroviral therapy in a resource-limited setting: an 11-year analytical cohort

Abstract

ABSTRACTBackgroundIt is projected that up to 19·6% of patients on ART in Sub-Saharan Africa will need second-line treatment by 2030, but the durability of such therapy remains unclear. This study investigated the durability of second-line ART and the factors associated with the viral rebound among patients on second-line ART in Uganda.MethodsA retrospective dynamic cohort of adults initiated on second-line ART after confirmed virological failure to first-line ART. Patients that had taken second-line for ≥6 months between 2007 and 2017 were included. Patients were followed until they experienced a viral rebound (Viral load ≥200copies/ml). Cumulative probability of viral rebounds and factors associated with viral rebound were determined using Kaplan-Meier methods and Cox proportional hazard models, respectively.Findings1101 participants were enrolled. At base-line, 64% were female, the median age was 37 years (IQR 31-43), median duration on first-line ART was 44months (IQR 27-67), and the median CD4 and viral load were 128 cells/ul (IQR 58-244) and 45978 copies/ml (IQR 13827-139583), respectively. During the 4757·21 person-years, the incidence density of viral rebound was 74·62 (95% CI 67·25- 82·80) per 1000 person-years. The probability of a viral round at 5 and 10 years was 0·29 (95% C: I 0·26 -0·32) and 0·623 (95%CI:0·55 -0·69), respectively. The median survival without experiencing a viral rebound was 8·7 years. Young adults (18-24) years (aHR 2·31 95 CI 1·25-4·27), high switch viral load ≥100,000copies/ml (aHR 1·53 95 CI 1·23- 1·91) and ATV/r based second-line (aHR1·53 95 CI 1·18-2·00) were associated with an increased risk viral rebound.InterpretationSecond-line regimens are fairly durable for eight years followed a rapid increase in the incidence of rebounds. A high viral load at switch, ATV/r based second-line, and young adulthood are risk factors associated with a viral rebound, which underscores the need for differentiated care services.