Rates and Predictors of Failure of First-line Antiretroviral Therapy and Switch to Second-line ART in South Africa

OBJECTIVES:To measure rates and predictors of virologic failure and switch to second-line antiretroviral therapy (ART) in South Africa. DESIGN:Observational cohort study. METHODS:We included ART-naive adult patients initiated on public sector ART (January 2000 to July 2008) at 5 sites in South Africa who completed ≥6 months of follow-up. We estimated cumulative risk of virologic failure (viral load ≥400 copies/mL with confirmation above varying thresholds) and switching to second-line ART. RESULTS:Nineteen thousand six hundred forty-five patients (29,935 person-years) had a median of 1.3 years of study follow-up (1.8 years on ART) and a median CD4 count of 93 (IQR39–155) cells per microliter at ART initiation. About 9.9% (4.5 per 100 person-years) failed ART in median 16 (IQR12–23) months since ART initiation, with median 2.7 months (IQR1.6–4.7) months between first elevated and confirmatory viral loads. By survival analysis, using a confirmatory threshold of 400 copies per milliliter, 16.9% [95% confidence interval (CI)15.4% to 18.6%] failed by 5 years on ART, but only 7.8% (95% CI6.6% to 9.3%) using a threshold of 10,000. CD4