Mitochondrial toxicity in HIV type-1-exposed pregnancies in the era of highly active antiretroviral therapy.
BACKGROUND
The aim of this study was to determine the effects of HIV type-1 (HIV-1) infection and antiretroviral therapy (ART) on placental mitochondria.


METHODS
HIV-1-infected pregnant women and HIV-1-uninfected controls were enrolled prospectively. Placental mitochondrial DNA (mtDNA) copy numbers were determined by quantitative PCR, subunits II and IV of cytochrome c oxidase (COX) were quantified by western blot and mitochondrial ultrastructure was evaluated by electron microscopy. Venous blood lactate was measured in newborns.


RESULTS
In total, 45 HIV-1-infected pregnant women on ART and 32 controls were included. Mean +/-sd mtDNA copy numbers were significantly reduced in ART and HIV-1-exposed placentas (240 +/-118 copies/cell) in comparison with controls (686 +/-842 copies/cell; P<0.001). The mean COX II/IV ratio was 48% lower in the investigational group compared with controls (P<0.001). There was no evidence of severe ultrastructural damage within mitochondria of HIV-1-infected ART-exposed placentas. Although lactate levels between newborns did not differ, they were negatively correlated with placental mtDNA levels. There was no clear association between mitochondrial parameters and a particular nucleoside reverse transcriptase inhibitor (NRTI), the number of NRTIs or time of NRTI exposure.


CONCLUSIONS
Placental tissue of HIV-1-infected ART-exposed pregnancies shows evidence of mtDNA depletion with secondary respiratory chain compromise. The clinical effects of this finding warrant further investigation.
Gingelmaier
Andrea
A
Department of Obstetrics and Gynaecology, Ludwig Maximilians University of Munich, Munich, Germany. andrea.gingelmaier@med.uni-muenchen.de
Grubert
Thomas A
TA
Kost
Bernd P
BP
Setzer
Bernhard
B
Lebrecht
Dirk
D
Mylonas
Ioannis
I
Mueller-Hoecker
Josef
J
Jeschke
Udo
U
Hiedl
Stephan
S
Friese
Klaus
K
Walker
Ulrich A
UA
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D004272:DNA, Mitochondrial / Q000032:analysis; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000821:virology*; D012189:Retrospective Studies
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D019344:Lactic Acid; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV