European Journal of Medical Research - Deutsche AIDS ...

June 27, 2007 EUROPEAN JOURNAL OF MEDICAL RESEARCH
95
D.39 (Vortrag)
Mitochondrial membrane potential of peripheral
mononuclear cells in therapy naïve HIV infected
patients
Sternfeld T. 1 , Tischleder A. 1 , Schuster M. 1 , Bogner J. 1 ,
German Competence Network HIV/AIDS
1 Medizinische Poliklinik, University of Munich, Department
of Infectious Diseases, München, Germany
Background: Mitochondrial toxicity was proposed to be
caused by antiretroviral therapy (ART). We analyzed the influence
of HIV infection on mitochondrial membrane potential
(MMP) as a marker of mitochondrial function of peripheral
mononuclear cells (PBMC) in patients without ART. The
correlation of clinical and immunological parameters to MMP
was investigated.
Methods: We studied 58 HIV infected patients never treated
with ART (mean CD4 cell count: 418/l, mean HI viral load
VL 76.000 cp/ml, mean duration of known HIV infection 53
months) and 8 HIV negative controls. MMP of PBMC was
measured by flow cytometry using the lipophilic dye JC-1.
Results: The mitochondrial membrane potential of HIV infected
patients was significantly lower than for HIV negative
controls (p=0.0001). In HIV infected patients, MMP of
PBMC was highly correlated to CD4 cell nadir (p=0.0001,
r=0.5), CD4 cell count at baseline (p=0.014, r=0.3), percentage
of CD4 positive cells (p=0.018, r=0.3), VL (p=0.001, r=-
0.4), and time since first positive HIV test (p=0.03, r=0.3). In
multivariate analysis, the CD4 cell count (p=0.001) and the
time since first positive HIV Test (p=0.04) remained significant
in contrast to HI viral load.
Conclusions: HIV-infection itself has a significant influence
on mitochondrial membrane potential of PBMC and is correlated
to the immune status of the patient.
D.40 (Vortrag)
Lipoatrophy and ubiquitous mtDNA depletion in
mice following long-term stavudine treatment
Stankov M. 1 , Schmidt R.E. 1 , Behrens G. 1 , Competence
Network HIV/AIDS
1 Hannover Medical School, Clinical Immunology, Hannover,
Germany
Background: Mitochondrial DNA (mtDNA) depletion has
been proposed as an important factor leading to peripheral
lipoatrophy in HIV-patients receiving antiretroviral therapy.
The extent to which mtDNA depletion occurs in other organs
and tissue in humans has not been evaluated and animal models
for lipoatrophy have not been established so far.
Methods: Groups of mice were treated with d4T, AZT or vehicle
(5-20 mice per group) for up to 15 weeks with daily human
doses adjusted for murine body surface area. In order to
better parallel the pharmacokinetics in humans drugs were administered
via oral gavage. MtDNA contend was determined
by Real-Time PCR in liver, muscle, heart, brain, and fat tissue.
Adiponectin and leptin were measured by ELISA in the
serum.
Results: Over a time period of 15 weeks mice receiving d4T
or AZT gained less weight (d4T from 25.3±0.17g to
29.1±0.2g; AZT from 25.8±0.2g to 30.2±0.2g) as compared to
control animals (from 26.1±0.2g to 34.8±0.2g) while no differences
in food and water intake were detected. Post mortem
examination revealed that mice on AZT treatment but particularly
animals receiving d4T had less of both peripheral as well
as central fat. Similarly, d4T treated animals had lower serum
adiponectin levels as compared to control mice (2.62±0.1
g/ml vs. 3.05±0.1 g/ml; p