Abstract
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.
Highlights
With the advent of antiretroviral therapy (ART), the incidence of perinatal HIV-1 transmission has decreased from 20-25% to less than 2% [1]
Using a basic Boolean search technique, we used the search terms “antiretroviral therapy” OR “nucleoside reverse transcriptase inhibitor (NRTI)” OR “protease inhibitor” AND “mitochondrial.” We were interested in the effects that in utero exposure to highly active ART (HAART) has on the cardiovascular system and what cardiac effects are present in this population during early childhood, since these are well-known developmental changes associated with drug toxicities
Several studies have found that mitochondrial DNA levels were below normal in HIV-uninfected children exposed to antiretroviral agents in utero [6,11,12]
Summary
With the advent of antiretroviral therapy (ART), the incidence of perinatal HIV-1 transmission has decreased from 20-25% to less than 2% [1]. ART prophylaxis during pregnancy is the standard treatment given to HIV-infected pregnant women, subjecting all infants born to HIV-positive mothers to drug toxicity. As the elimination of mother-to-child transmission of HIV becomes a reality, more patients are becoming exposed to antiretrovirals in utero, while long-term effects of these exposures remain unknown. Recent studies suggest that exposure to antiretroviral medications may have marked adverse effects, independent of HIV status [3,4]. Since the mid-1990s, highly active ART (HAART), a combination therapy of three or more HIV-suppressing drugs, has significantly improved the immunological status of the infected population, making HIV a manageable illness. Though mothers on HAART regimens may have optimal health, they expose their children to potent drugs and possible toxicity
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