Metabolic Complications of in utero Maternal HIV and Antiretroviral Exposure in HIV-exposed Infants

Background: Despite a wide body of literature supporting the use of antenatal antiretrovirals (ARV) for the prevention of mother-to-child transmission, there remains a need for continued monitoring as the intrauterine interval is a critical period during which fetal programming influences the future health and development of the child. Methods: We conducted a systematic review of the current literature addressing potential metabolic complications of in utero HIV and ARV exposure. We describe studies evaluating metabolic outcomes such as intrauterine and early postnatal growth, bone health and mitochondrial toxicity. Results: Overall, infants exposed to HIV/ARV do not appear to exhibit vastly compromised intrauterine or early postnatal growth. However, some studies on the effect of combination antiretroviral therapy on small for gestational age and low birth weight outcomes in low-middle income countries show a risk for small for gestational age/low birth weight while those in the United States do not. Postnatal growth to 1 year does not appear to be affected by intrauterine tenofovir exposure in African studies, but a US study found statistically significant differences in length for age z scores (LAZ) at 1 year. Little data exists on long-term bone health. Mitochondrial toxicity including abnormal mitochondrial morphology and DNA content, as well as neurologic deficits and death, have been demonstrated in HIV/ARV-exposed infants. Conclusion: Although gross measures of metabolic well-being appear to be reassuring, careful vigilance of even small risks for potential serious adverse effects to infants exposed to intrauterine HIV/ARVs is warranted as intrauterine fetal metabolic programming may substantially impact the future health of the child.