Changes in body composition and mitochondrial nucleic acid content in patients switched from failed nucleoside analogue therapy to Ritonavir-boosted Indinavir and Efavirenz

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; P =.003), L4 subcutaneous adipose tissue (+20 [35] cm(2); P < .001), mid-thigh subcutaneous adipose tissue (+5 [10] cm(2); P < .001), and L4 visceral adipose tissue (+11 [34] cm(2); 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.