More mitochondrial DNA depletion
1 September 2003. Related: Conference reports, Lipodystrophy and metabolic complications, Lipodystrophy Workshop (IWADRW) 5th Paris 2003.
David Nolan presented updated results from the Western Australian HIV Cohort showing that adipocyte depletion and mitochondrial toxicity are prominent in subcutaneous fat samples from 46 RTI-treated patients, compared to 24 HIV-positive treatment naïve patients and seven HIV-negative controls. [10]
Median mtDNA copies/cell was 1,288 in treatment naïve patients, and reduced by 81% to 240 copies/cell in 28 patients using d4T and by 41% to 726 copies/cell in 29 patients using AZT. Sequential biopsy samples showed significant changes in mtDNA within 2-12 months of initiated nucleoside therapy.
These changes correlated with adipocyte toxicity – reduced size and disorganised tissue architecture and marked macrophage infiltration.
Slides showed the differences between the ‘plump normal fatty cells’ seen in both HIV-negative and HIV-positive untreated individuals. Lipoatrophy is not a symptom of redistribution of fat – but one on specific fat cell damage in peripheral parts of the body.
Lopez and colleagues reported that HIV antiretroviral naïve patients had 68% mtDNA content with respect to HIV-negative control group, and that HIV itself could be a factor in mtDNA depletion [11] and Tebas and colleagues showed that mtDNA levels doubled on starting treatment, but fell again in patients when using d4T/ddI. [12]
Research on expression of SREBP-1 and apoB, showed increases in the synthesis and secretion of VLDL, and was suggested as an explanation for increases seen in levels of triglycerides and cholesterol. [13]
This article is part of a longer report from the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy, 8-11 July 2003, Paris. Part three of this report.
References:
Unless otherwise stated, all abstracts refer to the programme and abstracts from the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 8-11 July 2003, Paris and are published in Antiviral Therapy Volume 8 issue 4.
- Nolan D, Hammond E, McKinnon E et al – Subcutaneous fat tissue mitochondrial DNA depletion and adipose toxicity are strongly associated with nucleoside reverse transcriptase inhibitor (NRTI) therapy in HIV-infected patients. Abstract 18.
- Lopez S, Miro O, Martinez E et al – Does HIV infection itself have any effect on mitochondrial DNA content? Abstract 54.
- Tebas P, Mondy K, De Ronde A et al – Effects of different antiretroviral treatments on mitochondrial DNA levels in PBMCs of HIV-infected patients. Abstract 60.
- Shahmanesh M, Das S, Stolinski M et al – Effects of HIV infection, antiviral treatment and body fat changes on VLDL-apolipoprotein-B metabolism. Abstract 3.