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-rclated 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 < 100 cells per milliliter (HR 2.5; 95% CI: 1.8 to 3.6) but also plasma HIV RNA > 4 log(10) copies per milliliter at the time of the event (HR 1.9; 95% CI: 1.5 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.