Factors associated with clinical and virological failure in patients receiving a triple therapy including a protease inhibitor

Objective: To determine the predictors of virological and clinical failure in patients receiving a protease inhibitor as part of triple therapy. Methods: From the French Hospital Database on HIV, 1402 protease inhibitor-naive patients starting a highly active antiretroviral therapy regimen with ritonavir, saquinavir-hard gel capsule (hgc) or indinavir between July 1996 and March 1997, and with measured HIV RNA at baseline and at 12 months, were studied for progression to a new AIDS-defining event (ADE) or death. Virological failure was defined as plasma HIV RNA > 1000 copies/ml at 12 months. Multivariate analyses were performed using Cox models for clinical outcomes and logistic regression for virological outcomes. Results: During a median follow-up of 14.1 months, 94 (6.7%) patients experienced an ADE or died. At 12 months, 700 patients (49.9%) had virological failure. In the multivariate analysis, baseline CD4 cell count and viral load were found to be independent predictors of both virological and clinical failure. Neither the type of the first protease inhibitor taken nor previous antiretroviral therapy experience was associated with risk of clinical progression. For virological failure, the use of saquinavir-hgc was associated with a significant 1.96-fold increase in risk compared with indinavir; pre-treated patients were at higher risk than antiretroviral therapy-naive patients. Conclusion: In this study with large samples of patients, the use of saquinavir-hgc was associated with higher risk of virological failure at 12 months than were ritonavir and indinavir; no differences between protease inhibitors were found for clinical progression. As biases cannot be excluded, a longer duration of follow-up will be necessary to answer the question of whether the results are really discrepant or simply reflect the delay between virological failure and clinical manifestations. (C) 2000 Lippincott Williams & Wilkins.