More mitochondrial DNA depletion

David Nolan presented updated results form 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]

	HIV Treatment Bulletin Vol 4 No7 August / September 2003