title: Improvement of lipoatrophy by switching from efavirenz to lopinavir/ritonavir.
abstract: OBJECTIVE
  To assess whether changes in antiretroviral drugs other than thymidine nucleoside reverse transcriptase inhibitors (NRTI) may have a body fat impact in HIV-infected patients with lipoatrophy.
  
  
  METHODS
  Ninety-six-week phase IV, open-label, multicentre, pilot randomized trial. HIV-infected patients with moderate/severe lipoatrophy at one or more body sites despite long-term thymidine NRTI-free therapy were randomized to continue their efavirenz (EFV)-based antiretroviral regimen or to switch from EFV to lopinavir/ritonavir (LPV/r). The primary endpoint was the absolute change in limb fat mass measured by dual X-ray absorptiometry from baseline to 96 weeks. Changes in other body fat measurements, subjective perception of lipoatrophy, subcutaneous fat gene expression and plasma lipids were also assessed.
  
  
  RESULTS
  Thirty-three patients (73% men, median age 52 years) were recruited. At 96 weeks, absolute limb fat mass increased in the LPV/r arm vs. the EFV arm (estimated difference +1082.1 g; 95% CI +63.7 to +2103.5; P = 0.04); this difference remained significant after adjustment by gender, age, fat mass, body mass index and CD4 cell count at baseline. Subjective lipoatrophy perception scores also improved in the LPV/r arm relative to the EFV arm. Adipogenesis, glucose and lipid metabolism, and mitochondrial gene expression increased in the LPV/r arm compared with the EFV arm at 96 weeks. HDL cholesterol decreased in the LPV/r arm relative to the EFV arm.
  
  
  CONCLUSIONS
  Switching from EFV to LPV/r in HIV-infected patients with lipoatrophy may offer further limb fat gain beyond thymidine NRTI discontinuation, although this strategy decreased plasma HDL cholesterol and caused changes in subcutaneous fat gene expression that may be associated with increased insulin resistance.
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rojas
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Lonca
authors.affiliation: Hospital Universitari de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Imaz
authors.affiliation: Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Estrada
authors.affiliation: Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Asensi
authors.affiliation: Complexo Hospitalario Universitario de Vigo, Vigo, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Miralles
authors.affiliation: Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Montero
authors.affiliation: CETIR Grup Mèdic, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: del Rio
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Fontdevila
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Perez
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cruceta
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Arnedo
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Martínez
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D048588:Benzoxazines / Q000008:administration & dosage* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D004338:Drug Combinations; D005121:Extremities; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D061466:Lopinavir / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019438:Ritonavir / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D008055:Lipids; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir
keywords: efavirenz; lipoatrophy; lopinavir/ritonavir; pilot study; switch