Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts.
BACKGROUND
Nucleoside reverse transcriptase inhibitors (NRTIs) have been associated with mitochondrial toxicity in individuals receiving treatment. A report of two deaths in Europe attributed to mitochondrial dysfunction in HIV-uninfected infants with perinatal NRTI exposure prompted a review of five U.S. cohorts.


METHODS
Deaths in HIV-exposed children <60 months of age and HIV-uninfected or indeterminate were reviewed. Review included birth history; perinatal antiretroviral drug exposure; hospital, laboratory, and clinic records; death reports; autopsy results; and local physician queries. Deaths were classified as unrelated (Class 1), unlikely related (Class 2), possibly related (Class 3), or highly suggestive or proven relationship (Class 4), to mitochondrial dysfunction; sudden infant death syndrome (SIDS) was categorized separately.


CONCLUSIONS
Among over 20,000 children of HIV-infected women, over half of whom had been exposed to NRTIs, 223 died. In HIV-uninfected children, 26 deaths were attributed to Class 1, and 4 were attributed to SIDS. In HIV-indeterminate children, 141, 10, 3, and 0 were Classes 1, 2, 3, and 4, respectively; 33 were due to SIDS and 6 could not be classified. There was no indication that antiretroviral exposure was associated with Class 2 or 3 deaths, or deaths from SIDS. A search for mitochondrial dysfunction among living children in these cohorts is ongoing.
D019380:Anti-HIV Agents / Q000009:adverse effects*; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D017240:Mitochondrial Myopathies / Q000453:epidemiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D014481:United States
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors