TY - JOUR
T1 - A 48-week study of fat molecular alterations in HIV naive patients starting tenofovir/emtricitabine with lopinavir/ritonavir or efavirenz
AU - Domingo, Pere
AU - Gutierrez, Maria Del Mar
AU - Gallego-Escuredo, José Miguel
AU - Torres, Ferran
AU - Mateo, Maria Gracia
AU - Villarroya, Joan
AU - Lamarca, Karuna
AU - Domingo, Joan Carles
AU - Vidal, Francesc
AU - Villarroya, Francesc
AU - Giralt, Marta
PY - 2014/8/15
Y1 - 2014/8/15
N2 - 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.
AB - 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.
KW - Adipocyte differentiation
KW - Cytochrome b
KW - Efavirenz
KW - GRP78
KW - HALS
KW - Interleukin 18
KW - Lipoprotein lipase
KW - Lopinavir/ritonavir
KW - MCP-1
KW - Mitochondrial DNA
KW - ppar-γ
KW - Subcutaneous fat
KW - Tenofovir/emtricitabine
KW - TNF-α
U2 - 10.1097/QAI.0000000000000205
DO - 10.1097/QAI.0000000000000205
M3 - Article
VL - 66
SP - 457
EP - 465
IS - 5
ER -