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CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

Mocroft, Amandaa; Phillips, Andrew N.a; Gatell, Joseb; Horban, Andrejc; Ledergerber, Brunod; Zilmer, Kaie; Jevtovic, Djordjef; Maltez, Fernandog; Podlekareva, Dariah; Lundgren, Jens D.h,ifor The EuroSIDA study in EuroCOORD

doi: 10.1097/QAD.0b013e32835cb766
Clinical Science

Background: CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals.

Methods: Poisson regression was used to compare overall events (fatal or nonfatal AIDS, non-AIDS or death), AIDS events (fatal and nonfatal) or non-AIDS events (fatal or nonfatal) for specific nucleoside pairs and third drugs used with more than 1000 person-years of follow-up (PYFU) after 1 January 2001.

Results: Nine thousand, eight hundred and one patients contributed 42372.5 PYFU, during which 1203 (437 AIDS and 766 non-AIDS) events occurred. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global P-value = 0.084), and third drugs (global P-value = 0.031). As compared to zidovudine/lamivudine, patients taking abacavir/lamivudine [adjusted incidence rate ratio (aIRR) 1.22; 95% CI 0.99–1.49] and abacavir and one other nucleoside [aIRR 1.51; 95% CI 1.14–2.02] had an increased incidence of overall events. Comparing the third drugs, those taking unboosted atazanavir had an increased incidence of overall events compared with those taking efavirenz (aIRR 1.46; 95% CI 1.09–1.95).

Conclusion: There was little evidence of substantial differences between antiretrovirals in the incidence of clinical disease for a given CD4 cell count or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals.

aHIV Epidemiology and Biostatistics group, Research Department of Infection and Population Health, University College London, London, UK

bHospital Clinic i Provincial, Barcelona, Spain

cCentrum Diagnostyki i Terapii AIDS, Warsaw, Poland

dUniversity Hospital Zürich, University of Zurich, Zurich, Switzerland

eWest-Tallinn Central Hospital, Tallinn, Estonia

fThe Belgrade University School of Medicine Hospital for Infectious and Tropical Diseases, Belgrade, Serbia

gHospital Curry Cabral, Lisbon, Portugal

hCopenhagen HIV Program, University of Copenhagen

iDepartment of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark.

*Members of the steering committee are shown in appendix.

Correspondence to Professor Amanda Mocroft, Department of Infection and Population Health, University College London, Rowland Hill St., London, NW3 2PF, UK. Tel: +44 0 2078302239; fax: +44 0 2077941224; e-mail:

Received 28 August, 2012

Revised 30 October, 2012

Accepted 16 November, 2012

© 2013 Lippincott Williams & Wilkins, Inc.