Uncontrolled Viral Replication as a Risk Factor for Non-AIDS Severe Clinical Events in HIV-Infected Patients on Long-Term Antiretroviral Therapy: APROCO/COPILOTE (ANRS CO8) Cohort Study

OBJECTIVE:To determine risk factor for non-AIDS severe clinical events in HIV-infected patients on long-term combination antiretroviral therapy (cART). METHODS:A validation committee reviewed each severe clinical event that occurred in the APROCO/COPILOTE (ANRS CO8) cohort that enrolled 1281 patients in 1997-1999 at the initiation of cART containing protease inhibitor. Probability of the occurrence of a first non-AIDS, cART-related, and AIDS-defining event was estimated, and potential determinants were studied using Cox regression models. RESULTS:During a median follow-up of 7.3 years, the incidence of non-AIDS events was higher than that of cART-related and AIDS-defining events (10.5, 3.6, and 2.6 per 100 patient-years, respectively). Bacterial (mainly airway) infections were the most frequent non-AIDS events (23.4%) followed by non-AIDS-defining malignancies and cardiovascular events (both 9.5%). Factors independently associated with the occurrence of a first non-AIDS event were age >60 years [hazard ratio (HR) 2.1; 95% confidence interval (CI)1.3 to 3.2] and CD4 4 log10 copies per milliliter at the time of the event (HR 1.9; 95% CI1.5 to 2.5). CONCLUSION:Optimization and permanent continuation of long-term antiretroviral therapy in HIV-infected patients is the best strategy to prevent or reduce the occurrence of non-AIDS severe morbidity.