Changes in Body Composition and Mitochondrial Nucleic Acid Content in Patients Switched from Failed Nucleoside Analogue Therapy to Ritonavir‐Boosted Indinavir and Efavirenz
1HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, and 2Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 3National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, and 4St. Vincent’s Hospital, Sydney, and 5Department of Microbiology and Infectious Diseases, Flinders Medical Centre and Flinders University, Bedford Park, Australia; 6University of Denver, Denver, Colorado; 7Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre and International Antiviral Therapy Evaluation Centre, Amsterdam, The Netherlands
Background.
Body composition changes complicate antiretroviral therapy. Improvements in lipoatrophy after a switch in nucleoside reverse‐transcriptase inhibitors (NRTIs) have been demonstrated. We investigated 60 patients switching from failed NRTIs to ritonavir‐boosted indinavir and efavirenz.
Methods.Body composition (assessed by dual‐energy x‐ray absorptiometry scan and by single‐slice computed tomography of the abdomen through the level of the fourth lumbar vertebra [L4] and the mid–right thigh) and fasted metabolics were measured at the baseline time‐point at switch and at weeks 48 and 96 thereafter. Mitochondrial DNA and RNA were extracted from right‐thigh subcutaneous fat and peripheral‐blood mononuclear cells (PBMCs) at weeks 0 and 48. The primary end point was the change in mean limb fat over 48 weeks.
Results.At week 96, we observed increases in mean (standard deviation [SD]) limb fat (+620 [974] g; 
), L4 subcutaneous adipose tissue (+20 [35] cm2; 
), mid‐thigh subcutaneous adipose tissue (+5 [10] cm2; 
), and L4 visceral adipose tissue (+11 [34] cm2; 
), but we also observed reduced lean limb mass (−831 [1100] g; 
). Mean (SD) mtDNA content in subcutaneous fat and in PBMCs increased (+109 [274] and +45 [100] copies/cell, respectively). Improved virological control or immune recovery did not explain the results. Triglyceride, total cholesterol, estimated low‐density lipoprotein cholesterol, ratio of total cholesterol to high‐density lipoprotein cholesterol, and blood glucose levels deteriorated (i.e., had increased by 206%, 67%, 58%, 19%, and 6%, respectively, at week 96).
Conclusions.This regimen was associated with statistically significant but clinically modest increases in peripheral fat, visceral fat, and mitochondrial nucleic acid content. A predominantly adverse metabolic profile developed.
Received 24 November 2005; accepted 21 March 2006; electronically published 18 July 2006.
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Potential conflicts of interest: M.A.B. has received funding for conference attendance and travel from Merck, Roche, and Gilead and serves as an advisor to Roche. A.C. has received research grants and funding from Boehringer‐Ingelheim; consultancy fees from Boehringer‐Ingelheim, Bristol‐Myers Squibb, and GlaxoSmithKline; and lecture sponsorships from Abbott, Boehringer‐Ingelheim, Bristol‐Myers Squibb, and GlaxoSmithKline and has served on advisory boards for GlaxoSmithKline and Roche. M.L. has received sponsorship for consultancy and/or travel from Johnson and Johnson Research and GlaxoSmithKline. D.A.C. has received grants from and acted as a speaker and consultant for Merck Sharp & Dohme. P.P. and K.R. have acted as consultants and speakers for Merck. All other authors report no potential conflicts of interest.