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- Title
Mitochondrial function, morphology and metabolic parameters improve after switching from stavudine to a tenofovir-containing regimen.
- Authors
Gerschenson, Mariana; Kim, Courtney; Berzins, Baiba; Taiwo, Babafemi; Libutti, Daniel E.; Choi, Julia; Chen, Diana; Weinstein, Jill; Shore, Jessica; da Silva, Barbara; Belsey, Elizabeth; McComsey, Grace A.; Murphy, Robert L.
- Abstract
Objectives HIV-associated lipoatrophy has been associated with mitochondrial dysfunction induced by nucleoside reverse transcriptase inhibitor therapy. We hypothesize that lipid profiles and markers of mitochondrial function will improve in HIV-lipoatrophic patients switched to the nucleotide analogue tenofovir. Methods Ten patients receiving stavudine, lamivudine and lopinavir/ritonavir (Kaletra®) for over 6 years were switched from stavudine to tenofovir for 48 weeks. Subcutaneous fat tissue biopsies, fasting metabolic tests, HIV RNA, CD4 cell count and whole body dual energy X-ray absorptiometry (DEXA) scans were obtained at study entry and week 48. Mitochondrial DNA (mtDNA) copies/cell and mitochondrial morphology were assessed in adipose tissue biopsies, mtDNA 8-oxo-deoxyguanine in peripheral blood mononuclear cells, and glutathione (GSH) and F2-isoprostane in plasma. Results There was no change in limb fat mass by DEXA; however, trunk fat mass increased by 18.9% (P = 0.01). Fasting total cholesterol decreased by 33 mg/dL (P = 0.005) and serum glucose decreased by 4 mg/dL (P = 0.039). mtDNA copies/cell increased from 386 to 1537 (P Conclusions The results from this study demonstrate that systemic and peripheral fat mitochondria improve in patients switched to tenofovir following long-term exposure to stavudine, while continuing protease inhibitor therapy.
- Subjects
MITOCHONDRIAL pathology; METABOLISM; HIV-positive persons; ANTIRETROVIRAL agents; REVERSE transcriptase; ENZYME inhibitors; BIOMARKERS; LIPIDS; ADIPOSE tissues; BLOOD testing; BLOOD sugar
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2009, Vol 63, Issue 6, p1244
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkp100