Catia Marzolini1, Caroline Sabin, François Raffi, Marco Siccardi, Cristina Mussini, Odile Launay, David Burger, Bernardino Roca, Jan Fehr, Stefano Bonora, Amanda Mocroft, Niels Obel, Frederic-Antoine Dauchy, Robert Zangerle, Charalambos Gogos, Nicola Gianotti, Adriana Ammassari, Carlo Torti, Jade Ghosn, Genevieve Chêne, Jesper Grarup, Manuel Battegay. 1. aDivision of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland bDepartment of Infection and Population Health, University College London, London, UK cDivision of Infectious Diseases, University Hospital of Nantes, Nantes, France dDepartment of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK eClinic of Infectious Diseases, University of Modena, Modena, Italy fUniversity Paris Descartes, Paris, France gRadboud University Medical Centre, Nijmegen, the Netherlands hHospital General of Castellon, University of Valencia and University Jaume I, Valencia, Spain iDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and University of Zurich, Zurich, Switzerland jUnit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy kDepartment of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark lDepartment of Infectious and Tropical Diseases, HIV Unit, University Hospital Pellegrin, Bordeaux, France mMedical University Innsbruck, Innsbruck, Austria nDepartment of Internal Medicine, University Hospital of Patras, Patras, Greece oDepartment of Infectious Diseases, San Raffaele Scientific Institute, Milan pClinical Department, National Institute for Infectious Diseases 'L. Spallanzani', Rome qDivision of Infectious and Tropical Diseases, University and Ospedali Civili of Brescia, Brescia, Italy rParis Descartes University, EA 7327, Necker School of Medicine, Paris and APHP, UF de Thérapeutique en Immuno-Infectiologie, Hôpital de l'Hôtel-Dieu, Paris sUniversity of Bordeaux, ISPED, Centre INSERM U897-Epidémiologie Statistique, Bordeaux, France tCopenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark. *Catia Marzolini and Caroline Sabin contributed equally to this work.
Abstract
OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients. DESIGN: Observational European cohort collaboration study. METHODS: Eligible patients were antiretroviral-naïve with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load (<50 copies/ml) after treatment initiation, and time to viral load rebound (two consecutive viral load >50 copies/ml) after initial suppression over 5 years of follow-up. Recovery of CD4 cell count was evaluated 6 and 12 months after EFV initiation. Analyses were stratified by weight (kg) group (I - <55; II - >55, <80 (reference); III - >80, <85; IV - >85, <90; V - >90, <95; VI - >95). RESULTS: The study included 19,968 patients, of whom 9.1, 68.3, 9.1, 5.8, 3.5, and 4.3% were in weight groups I-VI, respectively. Overall, 81.1% patients attained virological suppression, of whom 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical difference was observed in time to undetectable viral load and virological rebound for heavier individuals compared to their normal-weight counterparts. Although heaviest individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range.
OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infectedpatients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infectedpatients. DESIGN: Observational European cohort collaboration study. METHODS: Eligible patients were antiretroviral-naïve with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load (<50 copies/ml) after treatment initiation, and time to viral load rebound (two consecutive viral load >50 copies/ml) after initial suppression over 5 years of follow-up. Recovery of CD4 cell count was evaluated 6 and 12 months after EFV initiation. Analyses were stratified by weight (kg) group (I - <55; II - >55, <80 (reference); III - >80, <85; IV - >85, <90; V - >90, <95; VI - >95). RESULTS: The study included 19,968 patients, of whom 9.1, 68.3, 9.1, 5.8, 3.5, and 4.3% were in weight groups I-VI, respectively. Overall, 81.1% patients attained virological suppression, of whom 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical difference was observed in time to undetectable viral load and virological rebound for heavier individuals compared to their normal-weight counterparts. Although heaviest individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range.
Authors: Jason D Robarge; Ingrid F Metzger; Jessica Lu; Nancy Thong; Todd C Skaar; Zeruesenay Desta; Robert R Bies Journal: Antimicrob Agents Chemother Date: 2016-12-27 Impact factor: 5.191
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