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 199 6 and March 1997, and with measured HIV RNA at baseline and at 12 months, w ere studied for progression to a new AIDS-defining event (ADE) or death. Vi rological failure was defined as plasma HIV RNA > 1000 copies/ml at 12 mont hs. Multivariate analyses were performed using Cox models for clinical outc omes and logistic regression for virological outcomes. Results: During a median follow-up of 14.1 months, 94 (6.7%) patients exper ienced an ADE or died. At 12 months, 700 patients (49.9%) had virological f ailure. In the multivariate analysis, baseline CD4 cell count and viral loa d were found to be independent predictors of both virological and clinical failure. Neither the type of the first protease inhibitor taken nor previou s antiretroviral therapy experience was associated with risk of clinical pr ogression. For virological failure, the use of saquinavir-hgc was associate d with a significant 1.96-fold increase in risk compared with indinavir; pr e-treated patients were at higher risk than antiretroviral therapy-naive pa tients. Conclusion: In this study with large samples of patients, the use of saquin avir-hgc was associated with higher risk of virological failure at 12 month s than were ritonavir and indinavir; no differences between protease inhibi tors were found for clinical progression. As biases cannot be excluded, a l onger duration of follow-up will be necessary to answer the question of whe ther the results are really discrepant or simply reflect the delay between virological failure and clinical manifestations. (C) 2000 Lippincott Willia ms & Wilkins.