The main objective of the present study was to ascertain if
mitochondrial DNA (
mtDNA) depletion as reported in HIV-infected patients with
highly active antiretroviral therapy (
HAART)-related
lipodystrophy (LD) implies any degree of mitochondrial respiratory chain (MRC) dysfunction. For this purpose, we evaluated HIV patients on different
HAART schedules with LD (group A; n=12) and on
HAART but without LD (group B; n=12), and untreated HIV-infected patients as controls (group C; n=24).
mtDNA content was determined on peripheral blood mononuclear cells (PBMCs) with a real-time PCR method. Complex II, III and IV activities of the MRC were simultaneously measured spectrophotometrically, as were spontaneous and stimulated oxygen consumption by PBMCs. Compared to controls (group C, 100%), patients with LD (group A) showed a decreased
mtDNA content (54%, P<0.001), which was associated with a decline in
complex III (62%, P<0.05) and IV activity (69%, P<0.05) (both complexes partially encoded by
mtDNA), but not in complex II activity (exclusively encoded by nuclear
DNA). Patients in group B showed a similar pattern of
mitochondrial dysfunction but to a lesser extent and without statistical significance. Respiratory activities in both treated groups (A and B) did not differ in comparison with controls. We conclude that
mtDNA depletion occurring during
HAART is associated with deficiencies in MRC complexes partially encoded by
mtDNA, which are detectable by PBMCs. Presented in 'Late Breakers and Hot Topics' session at 6th International Congress on
Drug Therapy in
HIV Infection, Glasgow, UK, 17-21 November 2002.