Seventh International Congress on Drug Therapy in HIV Infection Glasgow, UK - 14-17 November 2004

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL7.3

S. López¹, G. Garrabou¹, E. Martínez², P. Domingo³, J. Fontdevila⁴, J.M. Gatell², A.B. Infante¹, X. Gallart⁵, A. Milinkovic², F. Cardellach¹, J. Casademont¹, Miró^1
1Mitochondrial Research Laboratory, Muscle Research Unit, Department of Internal Medicine, Hospital Clinic, IDISAPS, Barcelona, Spain; ²Department of Infectious Diseases, Hospital Clinic, IDISAPS, Barcelona, Spain; ³Infectious Diseases Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; ⁴Department of Plastic Surgery, Hospital Clinic, IDIBAPS, Barcelona, Spain; ⁵Department of Orthopedic Surgery and Traumatology (ICMEQ), Hospital Clinic, IDIBAPS, Barcelona, Spain

OBJECTIVES: Mitochondrial (mt) DNA depletion in adipose tissue (AT) has been reported in patients with highly active antiretroviral therapy (HAART)-related lipodystrophy (LD). However, few studies have focused on the role of HIV itself or HAART in the AT mtDNA decrease. Similarly, the effects of mtDNA depletion on mitochondrial respiratory chain (MRC) function has not been evaluated. The aim of the study was to assess the mitochondrial amount, function and mtDNA content in AT from HIV patients previous to the development of LD.

METHODS: We studied AT mitochondria of 20 healthy controls (group A) and 17 HIV patients, the latter stratified in two subgroups: one antiretroviral naïve (n=8, group B) and the other one on HAART (n=9, group C). AT obtained from abdomen, thigh or arm, was immediately frozen in liquid nitrogen and stored at -80 C until being analized. We determined in AT homogenate the mitochondrial amount by the spectrophotometric assay of citrate synthase (CS) activity, as well as the mitochondrial respiratory chain (MRC) function, by the specific activity of cytochrome c oxidase (COX, complex IV of the MRC). MtDNA was measured by quantitative real-time PCR and expressed as the mtDNA to nuclear DNA ratio.

RESULTS: The mitochondrial amount was unaltered among groups. Conversely, groups B and C showed a marked decrease in mtDNA content per cell when compared with uninfected individuals (54% and 60% of the control value -100%-, respectively; p=0.001), as well as decreased absolute activity of COX (57% and 91% of the control value, respectively; p=0.07). Similar results were observed when mtDNA and COX activity were normalized by the mitochondrial amount (86% and 52% of the control value, respectively; p=ns, for normalized mtDNA content, and 72% and 66%, of the control value, respectively; p=0.02, for normalized COX activity). We found a positive correlation between mtDNA content and COX activity (R2=0.3, p<0.001).

CONCLUSIONS: Decreased mtDNA content in AT of HIV-infected patients is closely associated with decreased COX activity, irrespective of the presence of HAART, before LD appears. The exact role that HIV itself and HAART play in adipocyte changes remains to be determined.

Supported by 'Fundación para la Investigación y la Prevención del Sida en España' (FIPSE 3102-00 and 3161/00A), 'Fundació La Marató de TV3' (020210), 'Redes de Investigación en Mitocondrias (V2003-REDC06E-0) y Sida (173)' and 'Suport a Grups de Recerca' 2001/SGR/00379.

SESSION 7: ADVERSE EVENTS I

2004-11-14
PL7.3

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