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 [1,100] 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.
Boyd
Mark A
MA
HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. mark.boyd@fmc.sa.gov.au
Carr
Andrew
A
Ruxrungtham
Kiat
K
Srasuebkul
Preeyaporn
P
Bien
Darl
D
Law
Matthew
M
Wangsuphachart
Somjai
S
Krisanachinda
Anchali
A
Lerdlum
Sakalaya
S
Lange
Joep M A
JM
Phanuphak
Praphan
P
Cooper
David A
DA
Reiss
Peter
P
D015502:Absorptiometry, Photon; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000187:drug effects / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D004272:DNA, Mitochondrial; D017320:HIV Protease Inhibitors; D000077278:RNA, Mitochondrial; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019469:Indinavir; D012313:RNA; D018119:Stavudine; D019438:Ritonavir