TITLE

Changes in Body Composition and Mitochondrial Nucleic Acid Content in Patients Switched from Failed Nucleoside Analogue Therapy to Ritonavir-Boosted Indinavir and Efavirenz

AUTHOR(S)
Boyd, Mark A.; Carr, Andrew; Ruxrungtham, Kiat; Srasuebkul, Preeyaporn; Bien, Darl; Law, Matthew; Wangsuphachart, Somjai; Krisanachinda, Anchali; Lerdlum, Sakalaya; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Reiss, Peter
PUB. DATE
September 2006
SOURCE
Journal of Infectious Diseases;9/1/2006, Vol. 194 Issue 5, p642
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 mono nuclear 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; P = .003), L4 subcutaneous adipose tissue (+20 [35] cm² P<.001), mid-thigh subcutaneous adipose tissue (+5 [10] cm² and L4 visceral adipose tissue (+11 [34] cm² P = .01), but we also observed reduced lean limb mass (-831 [1100] g; P = .3). 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.
ACCESSION #
21900582

 

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