title: 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.
abstract: 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 <100 cells per milliliter (HR 2.5; 95% CI: 1.8 to 3.6) but also plasma HIV RNA >4 log10 copies per milliliter at the time of the event (HR 1.9; 95% CI: 1.5 to 2.5).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Fidéline
authors.initials: F
authors.lastname: Collin-Filleul
authors.forename: Michel
authors.initials: M
authors.lastname: Dupon
authors.forename: Pierre
authors.initials: P
authors.lastname: Dellamonica
authors.forename: Anne
authors.initials: A
authors.lastname: Waldner
authors.forename: Christophe
authors.initials: C
authors.lastname: Strady
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Catherine
authors.initials: C
authors.lastname: Leport
authors.forename: Vincent Le
authors.initials: VL
authors.lastname: Moing
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D019562:Viral Load; D014779:Virus Replication