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Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study

Cozzi-Lepri, Alessandroa; Phillips, Andrew Na; Clotet, Bonaventurab; Mocroft, Amandaa; Ruiz, Lidiab; Kirk, Olec; Lazzarin, Adrianoe; Wiercinska-Drapalo, Alicjaf; Karlsson, Andersg; Lundgren, Jens Dc,d; for the EuroSIDA Study Group

doi: 10.1097/QAD.0b013e328310e04f
Epidemiology and social

Objective(s): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death.

Design: Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window.

Methods: Standard survival analysis using Kaplan–Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed.

Results: We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38 814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4–3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7–22.9) in patients with no evidence of virological failure and 53% (39.3–66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2–2.7, P = 0.005).

Conclusion: Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.

aResearch Department of Infection & Population Health, Royal Free and University College Medical School, London, UK

bIrsiCaixa Foundation & Lluita contra la SIDA Foundation, Badalona, Spain

cCopenhagen HIV Programme, Faculty of Health Sciences, Panum Institute, University of Copenhagen, Denmark

dCentre for Viral Diseases@KMA, Rgishospitalet, Copenhagen, Denmark

eInstituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Vita-Salute University, Milan, Italy

fDepartment of Infectious Diseases, Medical University of Bialystok, Bialystok, Poland

gKarolinska University Hospital, Stockholm, Sweden.

*Members of the EuroSIDA Study Group are reported in the Acknowledgments.

Received 21 April, 2008

Revised 11 July, 2008

Accepted 16 July, 2008

Correspondence to Alessandro Cozzi-Lepri, BSc, MSc, PhD, Lecturer in Epidemiology and Biostatistics, Research Department of Infection & Population Health, Royal Free and University College Medical School, UCL, Hampstead Campus/site, Rowland Hill Street, London NW3 2PF, UK. Tel: +44 20 7794 0500 ext 36763; fax: +44 20 7794 1224; e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.