Effectiveness of second-line antiretroviral therapy: the impact of drug switches.

Including antiretroviral drug switches as a measure of ART failure could be more suitable than conventional measures to evaluate health outcomes in "real-world" settings. This is part of a historical cohort of HIV-infected adults who initiated ART from 2001-2005, and were followed up for a maximum of five years in three HIV/AIDS centers in Belo Horizonte, Brazil. Follow-up information included data from 2001-2010. All patients switched from first-line ART were included. Second-line ART effectiveness was measured as the time-to-ART failure. Failure was defined simulating two scenarios: (1) Clinical, immunological and virological failure (scenario 1); and scenario 1 plus ART switches (scenario 2). Descriptive analysis, Kaplan-Meier curves, log-rank test, and Cox proportional hazards model were performed. We identified 119 eligible patients; most had protease inhibitor (PI)-based regimens prescribed as second-line. The incidence of failure was different for the two scenarios (29.4% vs. 54.6% for scenario 1 and 2, respectively; p < 0.001). The main identifiers of failure were increase in viral load (31.1%) for scenario 1 and ART switches (42.8%) for scenario 2. Median duration on second-line ART was 36.8 vs. 19.8 months for scenario 1 and 2, respectively. In the Cox analysis of scenario 2, increased risk was found for patients given PI-based second-line regimens (HR = 2.26; 95% CI: 1.09-3.17). There is a high incidence of ART failure associated with PI-based regimens when ART switches are considered as an indicator of failure. This demonstrates the impact of ART switches in representing lack of ART effectiveness.