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 a ssociated 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 fi ve U.S. cohorts. Methods: Deaths in HIV-exposed children <60 months of age and HIV-uninfecte d or indeterminate were reviewed. Review included birth history; perinatal antiretroviral drug exposure; hospital, laboratory, and clinic records; dea th reports; autopsy results; and local physician queries. Deaths were class ified as unrelated (Class 1), unlikely related (Class 2), possibly related (Class 3), or highly suggestive or proven relationship (Class 4), to mitoch ondrial dysfunction; sudden infant death syndrome (SIDS) was categorized se parately. Results and Conclusions: Among over 20,000 children of HIV-infected women, over half of whom had been exposed to NRTIs, 223 died. In HIV-uninfected ch ildren, 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, an d 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.