title: The effects of HIV-1 subtype and ethnicity on the rate of CD4 cell count decline in patients naive to antiretroviral therapy: a Canadian-European collaborative retrospective cohort study.
abstract: BACKGROUND
  Ethnic differences have the potential to confound associations between HIV-1 subtype and immunologic progression. We compared declines in CD4 cell counts during untreated infection for the most prevalent HIV-1 subtypes, focusing on distinguishing between the effects of viral subtype and ethnicity.
  
  
  METHODS
  We combined data from 4 European and 6 Canadian cohorts, selecting adults in the stable chronic phase of untreated HIV infection. We estimated the change in square root CD4 cell count over time for subtypes and ethnicities using mixed models, adjusting for covariates selected for their potential effect on initial CD4 cell count or its decline.
  
  
  RESULTS
  Data from 9772 patients were analyzed, contributing 79 175 measurements of CD4 cell count and 24 157 person-years of follow-up. Overall, there were no appreciable differences in CD4 cell count decline for viral subtypes A, CRF01_AE, CRF02_AG, C and G compared with viral subtype B; whereas the decline in CD4 cell count in patients of African ancestry was considerably slower than in patients of other ethnicity. When ethnic groups were studied separately, there was evidence for slower declines in CD4 cell count in viral subtypes C, and possibly A and G, compared with viral subtype B in patients of African ancestry but not among patients of other ethnicities, suggesting an interaction between subtype and ethnicity.
  
  
  CONCLUSIONS
  Ethnicity is a major determinant of CD4 cell count decline; viral subtype differences may have existed but were small compared with the effect of ethnicity and were most apparent in patients of African ancestry. In developing countries, slower CD4 cell count declines among individuals of African descent may translate to a longer asymptomatic phase and increase the opportunity for HIV transmission.
authors.affiliation: Division of Infectious Diseases/Chronic Viral Illness Service, Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montréal, Que.
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.affiliation: Division of Infectious Diseases/Chronic Viral Illness Service, Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montréal, Que. ; Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Jim
authors.initials: J
authors.lastname: Young
authors.affiliation: Medical Research Council Clinical Trials Unit, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Dunn
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.affiliation: Centre du recherche INSERM U897 - Epidémiologie-Biostatistique, Institut de Santé Publique, d'Epidémioloie et de Développement (ISPED) Université Bordeaux, Bordeaux, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Dabis
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Vancouver, BC.
authors.forename: Richard
authors.initials: R
authors.lastname: Harrigan
authors.affiliation: Division of Infectious Diseases, St. Michael's Hospital, Toronto, Ont.
authors.forename: Darrell H
authors.initials: DH
authors.lastname: Tan
authors.affiliation: University Health Network, University of Toronto, Toronto, Ont.
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
authors.affiliation: Southern Alberta HIV Clinic, Calgary, Alta.
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.affiliation: The Ottawa Hospital - General Campus, Ottawa, Ont.
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Vancouver, BC. ; Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hogg
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ont.
authors.forename: Fiona
authors.initials: F
authors.lastname: Smaill