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Predictors of Virological Outcome and Safety in Primary HIV Type 1-Infected Patients Initiating Quadruple Antiretroviral Therapy: QUEST GW PROB3005

Hoen, Bruno ; Cooper, David A. ; Lampe, Fiona C. ; Perrin, Luc ; Clumeck, Nathan ; Phillips, Andrew N. ; Goh, Li-Ean ; Lindback, Stefan ; Sereni, Daniel ; Gazzard, Brian ; Montaner, Julio ; Stellbrink, Hans-Jurgen ; Lazzarin, Adriano ; Ponscarme, Diane ; Staszewski, Shlomo ; Mathiesen, Lars ; Smith, Don ; Finlayson, Robert ; Weber, Rainer ; Wegmann, Laurence ; Janossy, George ; Kinloch-de Loes, Sabine

In: Clinical Infectious Diseases, 2007, vol. 45, no. 3, p. 381-390

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    Titre
    • Predictors of Virological Outcome and Safety in Primary HIV Type 1-Infected Patients Initiating Quadruple Antiretroviral Therapy: QUEST GW PROB3005
    Auteur
    • Hoen, Bruno. Department of Infectious Diseases, University Medical Centre, Besancon
    • Cooper, David A.. National Centre in HIV Epidemiology and Clinical Research, University of New South Wales and St. Vincent's Hospital, Sydney, New South Wales
    • Lampe, Fiona C.. Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London
    • Perrin, Luc. Laboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, Geneva
    • Clumeck, Nathan. Department of Infectious Diseases, St. Pierre Hospital, Brussels, Belgium
    • Phillips, Andrew N.. Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London
    • Goh, Li-Ean. GlaxoSmithKline Research and Development, Greenford, United Kingdom
    • Lindback, Stefan. Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
    • Sereni, Daniel. Department of Internal Medicine, St. Louis Hospital, Paris, France
    • Gazzard, Brian. Kobler Centre, Chelsea
    • Montaner, Julio. John Ruedy Immune Deficiency Clinic, St. Paul's Hospital, University of British Columbia, Vancouver, Canada
    • Stellbrink, Hans-Jurgen. IPM Study Center, Hamburg
    • Lazzarin, Adriano. Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy
    • Ponscarme, Diane. Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire Saint-Louis, Paris, France
    • Staszewski, Shlomo. Klinikum der JW Goethe Universitat, Zentrum der Inneren Medizin, Frankfurt, Germany
    • Mathiesen, Lars. Hvidovre Hospital, Hvidovre, Denmark
    • Smith, Don. National Centre in HIV Epidemiology and Clinical Research, University of New South Wales and St. Vincent's Hospital, Sydney, New South Wales
    • Finlayson, Robert. Taylor Square Private Clinic, Surry Hills, Sydney, Australia
    • Weber, Rainer. Division of Infectious Diseases, Department of Internal Medicine, University Hospital, Zurich, Switzerland
    • Wegmann, Laurence. Laboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, Geneva
    • Janossy, George. Department of Immunology and Molecular Pathology, Royal Free and University College Medical School, London
    • Kinloch-de Loes, Sabine. Department of Infection and Immunity, Royal Free Center for HIV Medicine, Royal Free and University College Medical School, London
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Clinical Infectious Diseases, 2007, vol. 45, no. 3, p. 381-390. The University of Chicago Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:297726
    Summary
    Background. Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)-1 infection may confer long-term benefit. Methods. After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks. Results. One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with ⩽3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm3). By week 48, 36% of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm3 (IQR, -1 to 283 cells/mm3); 84.2% of patients had a viral load ⩽50 copies/mL, and 44.7% of patients had a viral load ⩽3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9-4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5-1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/million PBMCs (IQR, 2.4-3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2-1.9 log copies/million PBMCs); 33.3% of patients had an undetectable RNA level, and 9.5% of patients had an undetectable cell-associated DNA level. The median CD8+/CD38++ T cell count decreased from 459 cells/mm3 (IQR, 208-974 cells/mm3) to 33 cells/mm3 (IQR, 19-75 cells/mm3). Baseline CD8+/CD38++ T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load ⩽3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days). Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8+/CD38++ T cell count and cell-associated DNA level were predictive of achieving a viral load ⩽3 copies/mL