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Cardiovascular disease risk factors in HIV patients association with antiretroviral therapy. Results from the DAD study

Friis-Møller, Nina; Weber, Rainera; Reiss, Peterb; Thiébaut, Rodolphec; Kirk, Oled; Monforte, Antonella d'Arminioe; Pradier, Christianf; Morfeldt, Lindag; Mateu, Silviah; Law, Matthewi; El-Sadr, Wafaaj; De Wit, Stephank; Sabin, Caroline Al; Phillips, Andrew Nl; Lundgren, Jens D; for the DAD study group

Clinical Science

Objective: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies.

Design: Baseline data from 17 852 subjects enrolled in DAD, a prospective multinational cohort study initiated in 1999.

Methods: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral therapy.

Results: Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette smokers. Increased prevalence of elevated total cholesterol (≥ 6.2 mmol/l) was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 1.79; 95% confidence interval (CI), 1.45–2.22], PI but no NNRTI (OR, 2.35; 95% CI, 1.92–2.87), or NNRTI + PI (OR, 5.48; 95% CI, 4.34–6.91) compared to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level.

Conclusion: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.

From the DAD Coordinating Centre, Copenhagen HIV Programme, Hvidovre University Hospital, Copenhagen, Denmark, the aSwiss HIV Cohort Study (SHCS), Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland, bATHENA, Department of Medicine and Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, cAquitaine, Institut de Santé Publique, d'Epidémiologie et de Développement – Inserm U330, Bordeaux University Hospital, Bordeaux, France, dEuroSIDA, Copenhagen HIV Programme, Hvidovre University Hospital, Copenhagen, Denmark, eICONA, Department of Infectious Diseases, L Sacco Hospital, University of Milan, Milan, Italy, fNice Cohort, Service des Maladies Infectieuses et Tropicales et Medicine Interne, C.H.U. Nice Hopital de l'Archet, Nice, France, gHivBivus, Department of Infectious Diseases, Karolinska Hospital, Stockholm, Sweden, hBASS, Department of Clinical Pharmacology and Therapeutics, Autonomous University of Barcelona, Barcelona, Spain, iAHOD, National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia, jCPCRA, Division of Epidemiology, Columbia University School of Public Health, New York, USA, the kBrussels St. Pierre Cohort, Department of Infectious Diseases, C.H.U. Saint Pierre Hospital, Brussels, Belgium, and the lRoyal Free Centre for HIV Medicine and Department of Primary Care and Population Sciences, Royal Free and University College, London, UK. *See Appendix.

Correspondence to N. Friis-Møller, DAD Coordinating Centre, Copenhagen HIV Programme, Section 044, Hvidovre University Hospital, 2650 Copenhagen, Denmark. e-mail: nfm@cphiv.dk. http://www.cphiv.dk/dad/

Received: 14 March 2002; revised: 20 November 2002; accepted: 13 January 2003.

© 2003 Lippincott Williams & Wilkins, Inc.