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Increase in Mitochondrial DNA in PBMCs Following switch from d4T to Tenofovir
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Reported by Jules Levin
Spanish researchers reported at the 9th European AIDS Conference on changes in mitocondrial DNA in PBMCs, lipids, and lactate following a switch for patients from d4T to tenofovir (Viread).
Stavudine-associated mitochondrial toxicity may play a role in the etiology of lipoatrophy.
Thirty subjects with HIV-1 RNA <50 copies/ml on stavudine based HAART regimens with lipoatrophy were enrolled. Stavudine was switched to tenofovir, while the other drugs were maintained. Patients were prospectively followed. Fasting plasma samples were obtained for measuring lipidic profile and lactatemia. A real-time PCR assay was used to quantify mtDNA/nDNA ratio in PBMCs.
Baseline characteristics: mean age was 44 yr, 63% were males, median CD4 cell count was 481. Patients with lipoatrophy had a significantly lower mtDNA/nDNA ratio than healthy controls (n=20) and HIV-infected naïve patients (n=30) (median values: 47, 147 and 79, respectively).
After six months of tenofovir therapy none of the patients showed virologic failure and they had a median increase of 187 CD4 cell/µL. Changes in lactate levels, lipidic profile and mtDNA are shown in the table below. In no case tenofovir had to be withdrawn due to adverse effects. Significant improvements occurred for lactate, total cholesterol, HDL cholesterol, triglycerides, and the mtDNA/nDNA ratio. LDL cholesterol improved but it was not significant.
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Baseline (n=30) |
Month 3 (n=20) |
Month 6 (n=12) |
| Lactate |
1.68 |
1.51* |
1.36* |
| Total chol mg/dl |
246 |
231* |
217* |
| LDL-chol mg/dl |
126 |
119 |
110 |
| HDL-chol mg/ dl |
43.3 |
43.1 |
42.5 |
| Triglicerides mg/dl |
382 |
299* |
311* |
| MtDNA/nDNA |
47 |
76* |
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| *p>0.05 compared to baseline (Wilcoxon test) |
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The authors concluded switching from d4T to tenofovir was well tolerated and viral and immonologc success was maintained. Patients showed improvement in lipid profile, decrease in lactate levels, and amelioration of mfDNA depletion in PBMCs. (edit note: there is controversy around whether evaluating improvement in mtDNA is more reliable by looking at PBMCs or in tissue. Some researchers feel looking in tissue samples is more reliable).
Reference: 9TH EUROPEAN AIDS CONFERENCE (EACS),1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP. October 25 - 29, 2003 Warsaw, Poland. Abstract F16/4 - INCREASE IN MITOCHONDRIAL DNA IN PBMCS AND IMPROVEMENT OF LIPIDIC PROFILE AND LACTATE LEVELS IN PATIENTS WITH LIPOATROPHY WHEN STAVUDINE IS SWITCHED TO TENOFOVIR. Ribera E. (1), Sauleda S. (2), Paradiñeiro J.C. (1), Tejeda M. (2), Andreu A.L. (3), Marti R. (3), Garcia-Arumi E. (3), Crespo M. (1), Falcó V. (1), Ocaña I. (1), Pahissa A. (1). (1) Infectious Diseases Service, (2) Centre de Transfusio i Banc de Teixits, (3) Laboratori de Patologia Mitocondrial (CIBBIM), Hospitals Vall d'Hebron, Barcelona, Spain
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