ObjectiveTo study the predictors of virological rebound in patients having early virological response to protease inhibitor (PI)-containing regimen.Design and methodsAPROCO cohort study prospectively enrolled 1283 HIV-infected patients starting a PI-containing regimen in 1997–1999. Adherence to therapy was measured with self-administered questionnaires after 4 months of therapy (M4). Virological rebound was defined as a viral load (VL) > 500 copies/ml in patients having early virological response, defined as a VL < 500 copies/ml at M4. Predictors of time to virological rebound were studied with multivariate proportional hazards model.ResultsDuring a median follow-up of 20 months, virological rebound was observed in 32% of the 830 patients with early virological response. Virological rebound was more frequent when patients had received previous antiretroviral treatment [adjusted hazards ratio (HR) = 2.4;P< 0.0001], were younger (HR = 1.4 per each 10 years younger;P< 0.0001), had baseline CD4 cell count < 500 × 106/l (HR = 2.3;P< 0.001), had higher baseline VL (HR = 1.4 per each log10copies/ml higher;P< 0.001), reported low adherence to therapy at M4 (HR = 2.1;P< 0.001) or had stopped PI at M4 (HR = 1.7;P= 0.04).ConclusionInitiation of treatment at a stage of preserved immunity is associated with a more durable virological response under protease inhibitor. Every effort should be made to monitor and strengthen adherence to therapy, even in patients having early virological response.