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Session 90 Poster Session Incidence, Prevalence, and Pathogenic Correlates of Insulin Resistance and Lipodystrophy Syndrome Session Time: 4:30-6:30 pm Room 4E-F

686-T. Treatment with Dideoxynucleosides Is Reflected in Lowered Mitochondrial DNA in Subcutaneous Fat C. Cherry*1, M. Gahan1, S. Lewin2, 3, J. McArthur4, and S. Wesselingh1 1Monash Univ., Alfred Hosp., Melbourne, Australia; 2Royal Melbourne Hosp., Australia; 3Univ. of Melbourne, Australia; and 4Johns Hopkins Univ., Baltimore, MD Background: Nucleoside reverse transcriptase inhibitors, particularly dideoxynucleoside analogues (DDx), used in the treatment of HIV, inhibit mitochondrial DNA polymerase gamma in vitro. Mitochondrial DNA (mtDNA) depletion is proposed as the underlying mechanism of many of the in vivo side effects of these agents. Methods: 60 HIV-infected adults underwent clinical assessment and blood and tissue sampling. Assessment included details of treatment and clinical DDx toxicities: perceived body shape changes and evidence of sensory neuropathy (SN) (symptoms and at least one of sensory signs or reduced ankle jerks). mtDNA was quantified in peripheral blood mononuclear cells (PBMCs) and subcutaneous fat from punch skin biopsies using real-time PCR and plasma lactate assays were performed. Results were correlated with treatment, clinical and toxicity details, and multivariate analysis performed using a linear regression model. Results: 49 (82%) subjects were on combination antiretroviral therapy, including 33 (55%) currently taking at least one DDx. Punch biopsies were obtained from 2 sites on the lower limb. mtDNA in subcutaneous fat showed good inter-site reliability (r=0.53, p<0.0001) (Pearson correlation coefficient) and was lower in subjects currently on DDx than in those not currently taking DDx (mean [log10] 2.47 vs 2.74, p=0.002) (unpaired t test). mtDNA in PBMCs increased with patient age (r=0.35, p=0.01) but did not vary with treatment status. Among the subjects currently taking DDx, 21 (64%) had perceived body shape changes and 17 (52%) had SN. There was no difference in plasma lactate, mtDNA in subcutaneous fat, or mtDNA in PBMCs in those with and without either SN or body shape changes (p>0.1). Conclusions: Punch skin biopsies provide a minimally invasive method of collecting subcutaneous fat for reliable mtDNA quantification. The independent predictor for reduced mtDNA in this tissue is current DDx use. mtDNA in PBMCs increases with increasing age, but is independent of current DDx use. Plasma lactate and mtDNA in PBMCs or subcutaneous fat are independent of clinical DDx toxicities on a single measurement.

©2002 9th Conference on Retroviruses and Opportunistic Infections