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

BackgroundIt is projected that up to 19{middle dot}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{middle dot}21 person-years, the incidence density of viral rebound was 74{middle dot}62 (95% CI 67{middle dot}25- 82{middle dot}80) per 1000 person-years. The probability of a viral round at 5 and 10 years was 0{middle dot}29 (95% C: I 0{middle dot}26 -0{middle dot}32) and 0{middle dot}623 (95%CI:0{middle dot}55 -0{middle dot}69), respectively. The median survival without experiencing a viral rebound was 8{middle dot}7 years. Young adults (18-24) years (aHR 2{middle dot}31 95 CI 1{middle dot}25-4{middle dot}27), high switch viral load [≥]100,000copies/ml (aHR 1{middle dot}53 95 CI 1{middle dot}23- 1{middle dot}91) and ATV/r based second-line (aHR1{middle dot}53 95 CI 1{middle dot}18-2{middle dot}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.