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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

Ferry, Tristan MD, PhD*; Raffi, François MD, PhD; Collin-Filleul, Fidéline MD, PhD; Dupon, Michel§; Dellamonica, Pierre MD, PhD; Waldner, Anne MD; Strady, Christophe MD, PhD#; Chêne, Geneviève MD, PhD; Leport, Catherine MD, PhD**; Moing, Vincent Le MD, PhD††and the ANRS CO8 (APROCO-COPILOTE) Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 2009 - Volume 51 - Issue 4 - p 407-415
doi: 10.1097/QAI.0b013e3181acb65f
Clinical Science

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).

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.

From the *Service de Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Université Claude Bernard Lyon 1, Lyon, France; †Service de Maladies Infectieuses, Hôpital de l'Hotel-Dieu, CHU de Nantes, Nantes, France; ‡INSERM U897, Université Victor Segalen 2, Bordeaux, France; §Service de Maladies Infectieuses (B), Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France; ∥Service de Maladies Infectieuses, L'Archet 1, CHU de Nice, Université de Nice Sophia Antipolis, Nice, France; ¶Service de Maladies Infectieuses, CHU de Dijon, Dijon, France; #Service de Maladies Infectieuses, CHU de Reims, Reims, France; **Denis Diderot-Paris 7 University, Site Xavier Bichat-Laboratoire de Recherche en Pathologie Infectieuse, Paris, France; and ††Service des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac, CHU de Montpellier, UMR 145, Université Montpellier 1, Montpellier, France.

Received for publication August 28, 2008; accepted December 17, 2008.

Meetings at which parts of the data were presented: This work was partially presented as a poster (H-1722) at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 17-20, 2007, Chicago, IL.

All authors have no conflict of interest to declare.

Correspondence to: Dr. Vincent Le Moing, MD, PhD, Service des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac, CHU de Montpellier, 2 av Emile Bertin Sans, 34000 Montpellier, France (email:

© 2009 Lippincott Williams & Wilkins, Inc.