Sixth International Congress Drug Therapy in HIV Infection 17-21 November, 2002 Glasgow, UK

Objectives: To simultaneously evaluate mitochondrial DNA (mtDNA) content and mitochondrial respiratory chain (MRC) function in peripheral lymphocytes of HIV-infected patients who had developed lipodystrophy (LD) while on highly active antiretroviral therapy (HAART).

Design: Case and controls, cross-sectional.

Methods: We included HIV patients on diverse HAART schedules suffering from LD (group A; n=12) and, as controls, HIV-infected patients on HAART but without LD (group B; n=12) and untreated HIV-infected patients (group C; n=12). Control groups (B and C) were matched by age and gender respect to patients with LD (group A) and, for the control group B, by HAART regimen. Twenty millilitres of peripheral blood were used to isolate lymphocytes and perform all studies. Mitochondrial DNA content was calculated by a real time PCR method. Measurement of enzyme activity of complex III and IV of the MRC, both partially encoded by mtDNA, was performed spectrophotometrically. Spontaneous lymphocyte oxygen consumption, as well as stimulated with diverse MRC substrates, were also measured.

Results: With respect to the untreated patients (group C), patients with LD exhibited a mtDNA content of 61% (p<0.05), a complex III activity of 53% (p<0.01) and complex IV activity of 68% (p<0.05). For these altered parameters, no significant differences were found according HAART regimen contained a protease inhibitor, stavudine or both, as well as no significant association was found according the time on HAART. Respiratory activity, either spontaneous or stimulated, did not differ between patients with LD and controls.

Conclusions: Significant mtDNA depletion along with deficiencies in MRC complexes partially encoded by mtDNA is detectable in peripheral lymphocytes in patients on HAART and LD. According findings, lymphocytes could be a representative tissue to investigate and uncover early changes in mtDNA content and MRC function, perhaps even before LD becomes clinically evident.

Presenting author: Ò Miró

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1 Hospital Clínic, IDIBAPS, Barcelona, Spain.

2 Hospital Fundació-Asil de Granollers, Granollers, Barcelona, Spain.

3 Hospital Duran i Reynals, L’Hospitalet de Llobregat, Barcelona, Spain.

2002-11-17
PL14-1b
1b

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