Marina B Klein1, Jim Young2, David Dunn3, Bruno Ledergerber4, Caroline Sabin5, Alessandro Cozzi-Lepri5, Francois Dabis6, Richard Harrigan7, Darrell H Tan8, Sharon Walmsley9, John Gill10, Curtis Cooper11, Alexandra U Scherrer4, Amanda Mocroft5, Robert S Hogg12, Fiona Smaill13. 1. Division of Infectious Diseases/Chronic Viral Illness Service, Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montréal, Que. 2. 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. 3. Medical Research Council Clinical Trials Unit, London, UK. 4. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 5. Research Department of Infection and Population Health, University College London, London, UK. 6. Centre du recherche INSERM U897 - Epidémiologie-Biostatistique, Institut de Santé Publique, d'Epidémioloie et de Développement (ISPED) Université Bordeaux, Bordeaux, France. 7. Faculty of Health Sciences, Simon Fraser University, Vancouver, BC. 8. Division of Infectious Diseases, St. Michael's Hospital, Toronto, Ont. 9. University Health Network, University of Toronto, Toronto, Ont. 10. Southern Alberta HIV Clinic, Calgary, Alta. 11. The Ottawa Hospital - General Campus, Ottawa, Ont. 12. Faculty of Health Sciences, Simon Fraser University, Vancouver, BC. ; Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC. 13. Department of Medicine, McMaster University, Hamilton, Ont.
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. INTERPRETATION: 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.
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. INTERPRETATION: 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.
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