Mitochondrial toxicity in HIV type-1-exposed pregnancies in the era of highly active antiretroviral therapy

Abstract

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.