In utero nucleoside reverse transcriptase inhibitor exposure and signs of possible mitochondrial dysfunction in HIV-uninfected children.
BACKGROUND
There is equivocal evidence of in utero nucleoside reverse transcriptase inhibitor (NRTI) exposure and the occurrence of mitochondrial dysfunction (MD) in HIV-uninfected children born of HIV-infected women.


METHODS
The primary analysis included 1037 HIV-uninfected children born in 1991-2002 and enrolled in Pediatric AIDS Clinical Trials Group protocols 219/219C. Possible cases with unexplained signs of MD according to the Enquête Périnatale Française criteria were identified through retrospective review. Associations between overall in utero NRTI exposure, and trimester of first in utero NRTI exposure and possible MD were estimated with exact logistic regression.


RESULTS
Cases (n = 20) were significantly more likely to be male and to be born in earlier years than non-cases (n = 1017). There was no association between overall in utero NRTI exposure and MD. In unadjusted models there were higher odds of first in utero exposure in the third trimester to lamivudine (3TC) [odds ratio (OR), 3.76 versus 3TC unexposed; 95% confidence interval (CI), 1.09-11.78] and to zidovudine (ZDV) and 3TC in combination (ZDV/3TC) (OR, 3.29 vs. ZDV/3TC unexposed; 95% CI, 0.96-10.25) among cases than noncases. When adjusted for year of birth the odds of first exposure in the third trimester to 3TC (OR, 10.57; 95% CI, 1.93-75.61) and ZDV/3TC (OR, 9.84; 95% CI, 1.77-71.68) were significantly higher among cases than non-cases. Incomplete data precluded control of possible confounding by maternal viral load and psychoactive drug use.


CONCLUSIONS
Our study suggests that first exposure to 3TC or ZDV/3TC in the third trimester may be associated with the occurrence of possible MD. Further studies that rigorously assess MD and better control confounding are needed.
Brogly
Susan B
SB
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Ylitalo
Nathalie
N
Mofenson
Lynne M
LM
Oleske
James
J
Van Dyke
Russell
R
Crain
Marilyn J
MJ
Abzug
Mark J
MJ
Brady
Michael
M
Jean-Philippe
Patrick
P
Hughes
Michael D
MD
Seage
George R
GR
D019380:Anti-HIV Agents / Q000009:adverse effects*; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D019259:Lamivudine / Q000009:adverse effects; D008297:Male; D008431:Maternal-Fetal Exchange; D028361:Mitochondrial Diseases / Q000139:chemically induced*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D012737:Sex Factors; D015215:Zidovudine / Q000009:adverse effects
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D054303:HIV Reverse Transcriptase