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.

Autor: Domingo P; Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Gutierrez Mdel M; Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Gallego-Escuredo JM; 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., Torres F; 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., Mateo GM; Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Villarroya J; 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., de los Santos I; Infectious Diseases Unit, Hospital de la Princesa, Madrid, Spain., Domingo JC; 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., Villarroya F; 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., Del Rio L; CETIR, Barcelona, Spain., Estrada V; Infectious Diseases Unit, Hospital Clínico de San Carlos, Madrid, Spain., Giralt M; 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.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2014 Feb 26; Vol. 9 (2), pp. e89088. Date of Electronic Publication: 2014 Feb 26 (Print Publication: 2014).
DOI: 10.1371/journal.pone.0089088
Abstrakt: 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.
Databáze: MEDLINE