[ThAb0106] CHANGES IN ADIPOSE TISSUE MITOCHONDRIAL DNA QUALITY AND QUANTITY - RELATION TO HIV DISEASE, LIPOATROPHY AND EXPOSURE TO STAVUDINE

16th International AIDS Conference

Toronto, Canada - August 13 - 18, 2006

CHANGES IN ADIPOSE TISSUE MITOCHONDRIAL DNA QUALITY AND QUANTITY - RELATION TO HIV DISEASE, LIPOATROPHY AND EXPOSURE TO STAVUDINE

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. ThAb0106

P. Mallon¹, R. Sedwell¹, N. Duarte², A. Kelleher¹, D. Cooper¹, A. Carr³
¹ University of New South Wales, National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia, ² St Vincent's Hospital, Centre for Immunology, Sydney, Australia, ³ St Vincent's Hospital, HIV, Immunology and Infectious Diseases CSU, Sydney, Australia

BACKGROUND: In vivo, HIV and exposure to thymidine-analogue NRTI (tNRTI) decrease subcutaneous adipose tissue (SAT) mitochondrial DNA (mtDNA). tNRTI may inhibit DNA polymerase gamma (DNA pol-γ), causing chain termination of replicating mtDNA and mtDNA depletion. In this setting, mtDNA regions distal to the mtDNA transcription initiation site (TIS) should be preferentially depleted over proximal regions, causing changes in mtDNA quality.

METHODS: A cross-sectional study of three male groups; HIV negative (HIV-, n= 10), HIV+, antiretroviral naïve (HIV+, n=10) and HIV+, lipoatrophic (HIV+LA+, n=38 of whom 13 were receiving stavudine (d4t)). We extracted DNA from SAT biopsies and, using real-time PCR, examined mtDNA regions proximal (MTCYB) and distal (MTCO1) to the TIS with results expressed as copies/cell. MtDNA quality was determined using the distal/proximal mtDNA ratio.

RESULTS: Compared to HIV- group, MtDNA quantity of both MTCYB and MTCO1 were lower in the HIV+ group, lower again in the HIV+LA+ group and lowest in the HIV+LA+ group receiving d4t (see table). Compared to HIV-, the HIV+ groups had significantly lower mtDNA quality, but no difference in quality was observed between the HIV+ and HIV+LA+ groups, regardless of d4t exposure.


	HIV-	HIV+	HIV+LA+
		no	d4T	d4T
n	10	10	25	13
Age (yrs)	41 [9]	46 [6]^a	47 [5]^a	47 [6]^a
MTCYB (cps/cell)	2467 [836]	1293 [277]^a	818 [301]^a	268 [125]^a,b
MTCO1 (cps/cell)	2896 [1120]	1279 [374]^a	668 [262]^a,b	277 [130]^a,b
mtDNA ratio	1.2 [0.09]	1.0 [0.07]^a	1.06 [0.23]^a	0.95 [0.22]^a

[Median [IQR], a=P<0.05 vs HIV-, b=P<0.05 vs HIV+

CONCLUSIONS: Decreases in SAT mtDNA quantity and quality occur with HIV-infection. Greater mtDNA depletion in lipoatrophic patients (especially those on d4t), with no changes in mtDNA quality, regardless of ongoing d4t exposure, suggests that this further mtDNA depletion may arise through mechanisms other than inhibition of DNA pol-γ.

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2006-08-13
ThAb0106

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