A 48-week study of fat molecular alterations in HIV naive patients starting tenofovir/emtricitabine with lopinavir/ritonavir or efavirenz

Pere Domingo, Maria Del Mar Gutierrez, José Miguel Gallego-Escuredo, Ferran Torres, Maria Gracia Mateo, Joan Villarroya, Karuna Lamarca, Joan Carles Domingo, Francesc Vidal, Francesc Villarroya, Marta Giralt

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Abstract

BACKGROUND: Conflicting reports on the effects of efavirenz (EFV) and lopinavir/ritonavir (LPV/r) on subcutaneous adipose tissue (SAT) have been described. OBJECTIVE: The aim was to assess the 48-week molecular and clinical effects of LPV/r and EFV, combined with tenofovir/emtricitabine (TDF/FTC), on SAT of HIV-infected, antiretroviral-naive patients. METHODS: Forty-four adults were started on LPV/r or EFV combined with TDF/FTC. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by dual x-ray absorptiometry scans were obtained at study entry and week 48. Mitochondrial DNA (mtDNA) and transcripts for mtDNA-encoded proteins and genes involved in inflammation, adipocyte differentiation, and metabolism were assessed in paired SAT biopsies. RESULTS: Whole-body fat and limb fat mass increased in the LPV/r and EFV groups. MtDNA and cytochrome oxidase subunit II did not change, and cytochrome b increased significantly in EFV-treated patients. Tumor necrosis factor alpha and monocyte chemotactic protein-1 gene expression did not change in the LPV/r group, but these significantly increased in the EFV group. Interleukin 18 decreased in the LPV/r group, whereas it increased in the EFV group. CONCLUSIONS: Starting TDF/FTC plus EFV was associated with an increased expression of genes encoding for inflammatory cytokines in SAT in naive patients. Therapy with TDF/FTC plus LPV/r or EFV was associated with an increase in subcutaneous fat mass. Copyright © 2014 by Lippincott Williams & Wilkins.
Original languageEnglish
Pages (from-to)457-465
JournalJournal of Acquired Immune Deficiency Syndromes
Volume66
Issue number5
DOIs
Publication statusPublished - 15 Aug 2014

Keywords

  • Adipocyte differentiation
  • Cytochrome b
  • Efavirenz
  • GRP78
  • HALS
  • Interleukin 18
  • Lipoprotein lipase
  • Lopinavir/ritonavir
  • MCP-1
  • Mitochondrial DNA
  • ppar-γ
  • Subcutaneous fat
  • Tenofovir/emtricitabine
  • TNF-α

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    Domingo, P., Gutierrez, M. D. M., Gallego-Escuredo, J. M., Torres, F., Mateo, M. G., Villarroya, J., Lamarca, K., Domingo, J. C., Vidal, F., Villarroya, F., & Giralt, M. (2014). A 48-week study of fat molecular alterations in HIV naive patients starting tenofovir/emtricitabine with lopinavir/ritonavir or efavirenz. Journal of Acquired Immune Deficiency Syndromes, 66(5), 457-465. https://doi.org/10.1097/QAI.0000000000000205