European Journal of Medical Research - Deutsche AIDS ...

96 EUROPEAN JOURNAL OF MEDICAL RESEARCH
June 27, 2007
D.42 (Vortrag)
Mitochondrial toxicity in HIV- and ART-exposed
pregnancies
Gingelmaier A. 1 , Mylonas I. 1 , Walker U.A. 2 , Kost B. 1 ,
Kästner R. 1 , Sovric M. 1 , Grubert T.A. 3
1 Ludwig-Maximilians-Universität, Universitätsfrauenklinik
Innenstadt, München, Germany, 2 Medizinische
Universitätsklinik, Rheumatologie und klinische Immunologie,
Freiburg, Germany, 3 Gynäkologische Praxis, Ravensburg,
Germany
Objectives: Nowadays, nucleoside reverse transcriptase inhibitors
(NRTI´s) are administered routinely to HIV-infected
pregnant women for the reduction of vertical transmission of
HIV and for the treatment of the disease. The consequences
for the newborn like a potential mitochondrial toxicity are further
on unclear. The objectives of this study were:
a) evaluation of a mitochondrial toxicity of the HIV- and
NRTI-exposed placenta and
b) clinical manifestations in the newborns.
Methods: The quantity of the mitochondrial DNA (mtDNA)
of placental tissue was assessed using Taqman-PCR. Additonally,
an analysis of the mitochondrial morphology was performed
by electron microscope. The examined placentas derived
from HIV-infected pregnant women in comparison to
placentas of a control group. The HIV- and NRTI-exposed
newborns were examined clinically and the lactate level of the
peripheral blood was measured.
Results: The mt-DNA count per cell of 46 HIV- and NRTIexposed
placentas was reduced significant in comparison to
22 placentas of HIV-uninfected women (p=0.047). The morphology
of the mitochondria differed not significant between
the two groups. The lactate levels of the HIV- and NRTI-exposed
newborns were elevated considerable within the first
days of live, but no other symptoms occurred.
Conclusion: This study provided evidence that there could be
a mitochondropathy of the placentas and newborns of HIV-infected
mothers with ART treatment in pregnancy. To what extent
this will have an impact on the further live of the HIV-uninfected
child remains unclear.
D.43 (Vortrag)
Acute renal failure and rhabdomyolysis in a
patient treated with a Tenofovir containing
HAART regime, Statins and Fibrates -
a case report
Emmelkamp J. 1 , Thaler J. 1 , Oette M. 1 , Jensen B. 1 ,
Koch S. 1 , Bode J. 1 , Häussinger D. 1
1 Heinrich Heine Universität, Gastroenterologie, Hepatologie
& Infektiologie, Düsseldorf, Germany
Background: Tenofovir is a widely used NtRTI in patients
under HAART. Its use hase been associated with cases of renal
failure, predominantly in patients with preexisting renal
disease. Tenofovir is frequently adminstered in combination
with HIV protease inhibitors (PI) or non-nucleoside reverse
transcriptase inhibitors. Lipid lowering drugs such as HMG
CoA reductase inhibitors (statins) and fibrates are often used
in HIV-positive patients with dyslipidemia, as they can partly
reverse the alterations in lipid profiles due to HAART.
Case report: We report the case of a fourty year old woman
treated with a HAART regimen containing Tenofovir, Abacavir
and a PI. Kidney function was tested normal before initiating
Tenofovir therapy. For severe combined hyperlipidemia
and lipodystrophy she was prescribed pravastatin as
well as fenofibrate. The patient developed acute polyuric renal
failure (GFR 20ml/min, excretion >8000 ml/d) with following
hyperuremia (plasma urea 99 mg/dl) in combination
with rhabdomyolysis (CK11680 U/l). Glomerular fitration
rate returned to normal only three months after discontinuing
lipid lowering medication and switching ART to a double-PI
regimen.
Conclusions: In this patient, Tenofovir-induced renal insufficiency
led to impaired elimination of statins and fibrates with
predominant renal excretion, resulting in excessive rhabdomyolysis,
which in its turn exacerbated renal failure.
This case shows that bioavailability of lipid lowering drugs
may be influenced significantly due to altered pharmacokinetics
in Tenofovir-associated renal insufficiency. Physicians in
HIV-practice should be aware of the interactive potential of
these frequently coadministered drugs, even in patients with
no history of renal disease.
D.44 (Vortrag)
Atherogenic risk in HIV-infected children on
HAART due to triglycerides and small, dense LDL
Thiemeyer N. 1 , Neubert J. 1 , Verweel G. 2 , Königs C. 3 ,
Notheis G. 4 , Baumann U. 5 , Feiterna-Sperling C. 6 ,
Buchholz B. 7 , Richter W.O. 8 , Niehues T. 1
1 Heinrich Heine University, Centre for Pediatric, Düsseldorf,
Germany, 2 University of Rotterdam, Centre for Pediatric,
Rotterdam, Netherlands, 3 Johann Wolfgang Goethe
University, Centre for Pediatric, Frankfurt, Germany,
4 University Hospital Munich, Children`s Hospital, München,
Germany, 5 Medical School Hannover, Children`s University
Hospital, Hannover, Germany, 6 Charite Hospital, Centre for
Pediatric, Berlin, Germany, 7 University of Mannheim, Centre
for Pediatric, Mannheim, Germany, 8Institute for Lipoprotein
Metabolism, Windach, Germany
Background: Hypertriglyceridemia is associated with HIVinfection
whether treated or not. In non-HIV-infected subjects
atherogenic risk is thought to be due to small, dense low-density
lipoprotein (sdLDL) derived from triglycerid (TG) rich
lipoproteins.
Objective: To investigate whether different antiretroviral substance
classes are associated with elevation of TG and sdLDL.
Methods: We studied 66 children (9.0 ± 4.6 years old, 37
girls) who were treated with two NRTI plus NNRTI (n = 24,
group 1), two NRTI plus lopinavir/ ritonavir (n = 33, group
2), or lopinavir/ritonavir plus NNRTI (n = 9, group 3).
Among 13 different lipid parameters SdLDL- apolipoprotein
B-100 was measured after ultracentrifugation of serum in the
infranatant with a density > 1.44 g/ml. The data were compared
to data from healthy controls (n=28).
Results: The main findings were elevated TG in 7/24 children
of group 1, 18/33 of group 2 and 5/9 of group 3 (median TG:
94, 109, 229 mg/dl). Elevated sdLDL-ApoB-100 was found in
7/24 children of group 1 (3 with elevated TG), 7 children of
group 2 (3) and 5 children of group 3 (2). The mean concentration
of sdLDL-ApoB-100 did not differ significantly between
the three groups (11.6 ± 5.8; 11.9 ± 6.7; 14.4 ± 6.2
mg/dl). Eleven children have a high capacity to catabolize
TG-rich VLDL producing elevated sdLDL leading to normal
fasting TG.
Conclusions: No single antiretroviral substance class is associated
with elevation of TG and sdLDL. In our cohort 22/66