There has been a dramatic decrease in perinatal HIV infection in the United States and other resource‐rich countries since 1994, when Pediatric AIDS Clinical Trials Group protocol 076 showed that administration of zidovudine to the HIV‐infected woman during pregnancy and labor and to her newborn reduced the risk of mother‐to‐child HIV transmission by nearly 70%. Subsequently, it was recognized that the use of combination antiretroviral (ARV) drug regimens during pregnancy could further reduce transmission. Current recommendations for the prevention of mother‐to‐child transmission in the United States include the use of ARV combination therapy during pregnancy for women with HIV RNA loads >1000 copies/mL, with the use of zidovudine prophylaxis alone restricted to women with HIV RNA loads <1000 copies/mL. Although mother‐to‐child transmission in the United States has dramatically decreased, from 25% to <2%, this significant advance entails the in utero and neonatal exposure of many infants to 1 drug of unknown toxicity. Although data regarding the short‐term safety of exposure to ARV drugs for uninfected infants have been reassuring, there is limited information about long‐term effects. Preclinical data have indicated that some ARV drugs, particularly those in the nucleoside‐analogue reverse‐transcriptase inhibitor (NRTI) class, may be associated with mitochondrial dysfunction, and it has been suggested that some infants with in utero or neonatal exposure to these drugs may have laboratory or clinical signs of mitochondrial dysfunction. The French Perinatal Cohort Study Group studied 2644 uninfected HIV‐ and ARV‐exposed children, and they reported an 18‐month incidence of clinical symptoms (primarily neurologic) of mitochondrial dysfunction of 0.26% and a mortality incidence of 0.07%. The same group also reported an increased risk of simple febrile seizures during the first 18 months of life and persistently lower (but clinically insignificant) neutrophil, lymphocyte, and platelet counts in infants associated with in utero NRTI exposure. Although these clinical abnormalities and mortality findings have not been duplicated to date in other cohorts in the United States and Europe, the European Collaborative Study reported similar hematologic abnormalities in uninfected infants with in utero or neonatal ARV exposure.
We report here an analysis of data from the Women Infant Transmission Study (WITS), a longitudinal cohort of HIV‐infected mothers and their infants from the United States and Puerto Rico that explores the effect of perinatal exposure to ARV drugs on hematologic and lymphocytic parameters in HIV‐uninfected infants and children during the first 2 years of life.