The effects of fetal and childhood exposure to antiretroviral agents

Purpose: The compliant use of combination antiretroviral therapy has virtually eliminated perinatal HIV transmission. Although antiretroviral drug toxicities in adults have been well documented, the effects of fetal and early childhood exposure to antiretroviral drugs on children of HIV-positive mothers are not well known. Methods: We searched the Pub Med database, reviewed publications, and selected abstracts on the use of antiretroviral agents to prevent HIV transmission and their effects on growth and cardiac endpoints in fetal and postnatal life. Results: The link between nucleoside analogs and mitochondrial dysfunction is controversial, and the association between in utero antiretroviral exposure and mitochondrial dysfunction in children is unclear. In utero exposure to antiretroviral therapy has effects on the heart, regardless of HIV status, including improved cardiac function but also reduced cardiac mass of unclear future clinical significance. Preterm delivery and impaired somatic growth have been reported in infants exposed to antiretrovirals, but results are inconsistent. In utero exposure has also been associated with below-normal hematologic parameters. In HIV-infected children, cumulative postnatal exposure to antiretroviral agents is associated with metabolic disturbances and an increased risk for cardiovascular disease. Conclusion: Antiretroviral therapy is effective in preventing perinatal HIV transmission but may be associated with adverse long-term side effects in exposed infants. Further clinical trials and longitudinal monitoring are needed to understand the long-term effects of in utero exposure to antiretroviral agents.