A 48-Week Study of Fat Molecular Alterations in HIV Naive Patients Starting Tenofovir/Emtricitabine With Lopinavir/Ritonavir or Efavirenz

Domingo, Pere MD, PhD*; Gutierrez, Maria del Mar MD*; Gallego-Escuredo, José Miguel PhD†,‡; Torres, Ferran MD, PhD§; Mateo, Maria Gracia MD*; Villarroya, Joan MD, PhD*,†,‡; Lamarca, Karuna MD*; Domingo, Joan Carles PhD†,‡; Vidal, Francesc MD, PhD; Villarroya, Francesc PhD†,‡; Giralt, Marta PhD†,‡

JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 August 2014 - Volume 66 - Issue 5 - p 457–465
doi: 10.1097/QAI.0000000000000205
Basic and Translational Science

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.

*Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain;

Department of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain;

CIBER Fisiopatologia de la Obesidad y Nutrición, Barcelona, Spain;

§Biostatistics and Data Management Platform, IDIBAPS, Hospital Clinic; Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; and

Infectious Diseases Unit, Department of Internal Medicine, Hospital Universitari Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.

Correspondence to: Dr Pere Domingo, MD, PhD, Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Avenue, Sant Antoni Maria Claret, 167, Barcelona 08025, Spain (e-mail: pdomingo@santpau.cat).

Supported in part by Fondo de Investigaciones Sanitarias (FIS PI10/2635, PI11/02,512, and PI11/00,376), Fundación para la Investigación y Prevención del SIDA en España (FIPSE 36610, 36572/06), Ministerio de Sanidad, Politica Social e Igualdad (EC11-293), Programa de Suport als Grups de Recerca AGAUR (2009 SGR 1061), and Red de Investigación en SIDA (RIS RD06/006/0022, RD06/0006/1004, RD012/0017/0014) and by an unrestricted grant from Abbott Laboratories. P.D. and F.V. are supported by grants from the Programa de Intensificación de Investigadores, Instituto de Salud Carlos III (INT12/383, INT13/232, and INT11/240). The funding sources were not involved in the design of the study, in the collection and analysis of data, or in writing the report. All authors had access to the data used in the analyses, and the lead author reviewed the full data report. The full study data were available to all authors. The decision to submit the paper for publication was made by P.D., F.V., and M.G.

The authors have no conflicts of interest to disclose.

P.D. and M.D.M.G. contributed equally to this work.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received January 12, 2014

Accepted March 27, 2014

© 2014 by Lippincott Williams & Wilkins