Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy

Marin, Benoîta,b,c; Thiébaut, Rodolphea,b; Bucher, Heiner Cd; Rondeau, Virginiea,b; Costagliola, Dominiquee,f; Dorrucci, Mariag; Hamouda, Osamahh; Prins, Mariai; Walker, Sarahj; Porter, Kholoudj; Sabin, Carolinek; Chêne, Genevièvea,b

doi: 10.1097/QAD.0b013e32832e9b78
Epidemiology and social

Objective: To assess whether immunodeficiency is associated with the most frequent non-AIDS-defining causes of death in the era of combination antiretroviral therapy (cART).

Design: Observational multicentre cohorts.

Methods: Twenty-three cohorts of adults with estimated dates of human immunodeficiency virus (HIV) seroconversion were considered. Patients were seroconverters followed within the cART era. Measurements were latest CD4, nadir CD4 and time spent with CD4 cell count less than 350 cells/μl. Outcomes were specific causes of death using a standardized classification.

Results: Among 9858 patients (71 230 person-years follow-up), 597 died, 333 (55.7%) from non-AIDS-defining causes. Non-AIDS-defining infection, liver disease, non-AIDS-defining malignancy and cardiovascular disease accounted for 53% of non-AIDS deaths. For each 100 cells/μl increment in the latest CD4 cell count, we found a 64% (95% confidence interval 58–69%) reduction in risk of death from AIDS-defining causes and significant reductions in death from non-AIDS infections (32, 18–44%), end-stage liver disease (33, 18–46%) and non-AIDS malignancies (34, 21–45%). Non-AIDS-defining causes of death were also associated with nadir CD4 while being cART-naive or duration of exposure to immunosuppression. No relationship between risk of death from cardiovascular disease and CD4 cell count was found though there was a raised risk associated with elevated HIV RNA.

Conclusion: In the cART era, the most frequent non-AIDS-defining causes of death are associated with immunodeficiency, only cardiovascular disease was associated with high viral replication. Avoiding profound and mild immunodeficiency, through earlier initiation of cART, may impact on morbidity and mortality of HIV-infected patients.

Author Information

aINSERM, U897, Bordeaux, France

bUniversité Victor Segalen Bordeaux 2, Bordeaux School of Public Health (ISPED), Bordeaux Cedex, France

cCHU Limoges, Unité Fonctionnelle de Recherche Clinique et Biostatistique, Limoges, France

dBasel Institute for Clinical Epidemiology, University Hospital Basel, Basel, Switzerland

eINSERM, U 943, Paris, France

fUPMC Univ Paris 06, UMR S 943, Paris, France

gIstituto Superiore di Sanità, Dipartimento di Malattie Infettive, Reparto di Epidemiologia, Rome, Italy

hRobert Koch Institute, Department of Infectious Disease Epidemiology, Berlin, Germany

iAmsterdam Health Service, Cluster Infectious Diseases, Department of Research, Amsterdam, the Netherlands

jMedical Research Council Clinical Trials Unit, UK

kDivision of Population Health, Research Department of Infection and Population Health, Royal Free and University College Medical School, London, UK.

Received 2 March, 2009

Revised 25 May, 2009

Accepted 26 May, 2009

Correspondence to Professor Geneviève Chêne, MD, PhD, INSERM U897, Bordeaux School of Public Health (ISPED), Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, F-33076 Bordeaux Cedex, France. Tel: +33 5 57 57 12 57; fax: +33 5 57 57 11 72; e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.