title: Effects of switching from stavudine to raltegravir on subcutaneous adipose tissue in HIV-infected patients with HIV/HAART-associated lipodystrophy syndrome (HALS). A clinical and molecular study.
abstract: HIV-1/HAART-associated lipodystrophy syndrome (HALS) has been associated with exposure to stavudine (d4T) through mitochondrial dysfunction. We performed a 48-week study to assess the effects of switching from d4T to raltegravir (RAL) on metabolic and fat molecular parameters of patients with HALS. Forty-two patients with HALS and a median exposure to d4T > 7 years were switched to RAL and followed for 48 weeks. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by DEXA were obtained at baseline and week 48. mtDNA and gene transcripts for PPAR gamma, adiponectin, cytochrome b, Cox IV, TNF alpha, MCP-1 and CD68 were assessed in paired subcutaneous fat tissue biopsies. Lipid parameters, fasting glucose, insulin, and HOMA-IR did not change significantly. Whole body fat (P = 0.0027) and limb fat mass (P<0.0001) increased from baseline. Trunk/limb fat ratio (P = 0.0022), fat mass ratio (P = 0.0020), fat mass index (P = 0.0011) and percent leg fat normalized to BMI (P<0.0001) improved after 48 weeks. Relative abundance of mtDNA, expression of PPAR gamma, adiponectin, Cyt b, and MCP-1 genes increased, whereas Cox IV, TNF alpha, and CD68 did not change significantly from baseline. Switching from d4T to RAL in patients with HALS is associated with an increase in limb fat mass and an improvement in markers of adipocyte differentiation and mitochondrial function in SAT.
authors.affiliation: Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: María del Mar
authors.initials: Mdel M
authors.lastname: Gutierrez
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Fisiopatología de la Obesidad y Nutrición, Centros de Investigación Biomédica en Red (CIBER), Santiago de Compostela, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Gallego-Escuredo
authors.affiliation: Biostatistics and Data Management Platform, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Torres
authors.affiliation: Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Gracia María
authors.initials: GM
authors.lastname: Mateo
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Institut de Recerca del Hospital de la Santa Creu i Sant Pau, Barcelona, Spain ; Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Fisiopatología de la Obesidad y Nutrición, Centros de Investigación Biomédica en Red (CIBER), Santiago de Compostela, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Villarroya
authors.affiliation: Infectious Diseases Unit, Hospital de la Princesa, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: de los Santos
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Fisiopatología de la Obesidad y Nutrición, Centros de Investigación Biomédica en Red (CIBER), Santiago de Compostela, Spain.
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Domingo
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Fisiopatología de la Obesidad y Nutrición, Centros de Investigación Biomédica en Red (CIBER), Santiago de Compostela, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.affiliation: CETIR, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Del Rio
authors.affiliation: Infectious Diseases Unit, Hospital Clínico de San Carlos, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Estrada
authors.affiliation: Department of Biochemistry and Molecular Biology and Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Institute of Biomedicine, University of Barcelona, Barcelona, Spain ; Fisiopatología de la Obesidad y Nutrición, Centros de Investigación Biomédica en Red (CIBER), Santiago de Compostela, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Giralt
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001823:Body Composition; D004272:DNA, Mitochondrial / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use*; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D018119:Stavudine