Antiretroviral exposure and lymphocyte mtDNA content among uninfected infants of HIV-1-infected women.
OBJECTIVE
Concern for potential adverse effects of antiretroviral (ARV) chemotherapy used to prevent mother-to-child HIV transmission has led the US Public Health Service to recommend long-term follow-up of ARV-exposed children. Nucleoside reverse transcriptase inhibitor ARV agents can inhibit DNA polymerase gamma, impairing mitochondrial DNA (mtDNA) synthesis and resulting in depletion or dysfunction.


METHODS
We measured the mtDNA content of stored peripheral blood mononuclear cells (PBMCs) of 411 healthy children who were born to HIV-uninfected women and 213 uninfected infants who were born to HIV-infected women with or without in utero and neonatal ARV exposure. Cryopreserved PBMC mtDNA was quantified by using the Primagen Retina Mitox assay.


RESULTS
Geometric mean PBMC mtDNA levels were lower at birth in infants who were born to HIV-infected women. Among HIV-exposed children, mtDNA levels were lowest in those who were not exposed to ARVs, higher in those with exposure to zidovudine alone, and higher still in those with combination nucleoside reverse transcriptase inhibitor exposure. A similar pattern was observed in the corresponding women. Levels of mtDNA increased during the first 5 years of life in all HIV-exposed children but achieved normal levels only in those with ARV exposure.


CONCLUSIONS
Levels of mtDNA are lower than normal in HIV-exposed children. Contrary to expectation, PBMC mtDNA levels are significantly higher in ARV-exposed, HIV-uninfected infants and their infected mothers compared with ARV-unexposed infants and women. By 5 years, levels of PBMC mtDNA rise to normal concentrations in ARV-exposed children but remain depressed in ARV-unexposed children.
Aldrovandi
Grace M
GM
Saban Research Institute of Childrens Hospital Los Angeles, University of Southern California, Los Angeles, California 90027, USA. galdrovandi@chla.usc.edu
Chu
Clara
C
Shearer
William T
WT
Li
Daner
D
Walter
Jan
J
Thompson
Bruce
B
McIntosh
Kenneth
K
Foca
Marc
M
Meyer
William A
WA
Ha
Belinda F
BF
Rich
Kenneth C
KC
Moye
Jack
J
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000097:blood / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D008137:Longitudinal Studies; D009000:Monocytes / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011263:Pregnancy Trimester, Third; D011297:Prenatal Exposure Delayed Effects; D012016:Reference Values; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine