title: Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Catia
authors.initials: C
authors.lastname: Marzolini
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Marco
authors.initials: M
authors.lastname: Siccardi
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.forename: David
authors.initials: D
authors.lastname: Burger
authors.forename: Bernardino
authors.initials: B
authors.lastname: Roca
authors.forename: Jan
authors.initials: J
authors.lastname: Fehr
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Frederic-Antoine
authors.initials: FA
authors.lastname: Dauchy
authors.forename: Robert
authors.initials: R
authors.lastname: Zangerle
authors.forename: Charalambos
authors.initials: C
authors.lastname: Gogos
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Adriana
authors.initials: A
authors.lastname: Ammassari
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Genevieve
authors.initials: G
authors.lastname: Chêne
authors.forename: Jesper
authors.initials: J
authors.lastname: Grarup
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
mesh_terms: D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000008:administration & dosage* / Q000627:therapeutic use*; D001835:Body Weight; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz