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Metabolic complications of in utero maternal HIV and antiretroviral exposure in HIV-exposed infants.

ABSTRACT: 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.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.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.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.

SUBMITTER: Jao J

PROVIDER: S-EPMC4055505 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Metabolic complications of in utero maternal HIV and antiretroviral exposure in HIV-exposed infants.

Jao Jennifer J Abrams Elaine J EJ

The Pediatric infectious disease journal 20140701 7

<h4>Background</h4>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.<h4>Methods</h4>We conducted a systematic review of the current literature addressing potential metabolic complications of in utero HIV and ARV exposure. We ...[more]

PMID: 24378947

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Project description:Most studies examining the association of prenatal antiretroviral (ARV) exposures with congenital anomalies (CAs) in children born to human immunodeficiency virus (HIV)-infected women have been reassuring, but some evidence suggests an increased risk with specific ARV agents.To evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children.Prospective cohort study design. The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23, 2007, and June 18, 2012.First-trimester exposure to any ARV and to specific ARV medications.The primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures, adjusting for demographic and maternal characteristics.Congenital anomalies occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI, 5.85%-7.82%); 242 major CAs were confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence of CAs increased significantly among successive birth cohorts (3.8% for children born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no association of first-trimester exposures with CAs was found for any ARV, for combination ARV regimens, or for any drug class. No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55) CAs.Few individual ARVs and no drug classes were associated with an increased risk of CAs in HIV-exposed infants after adjustment for calendar year and maternal characteristics. While the overall risk remained low, a relative increase was observed in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy use during pregnancy still outweigh such risks, although further studies are warranted.

Project description:IntroductionThere is a growing population of children who are HIV-exposed and uninfected (HEU) with the successful expansion of antiretroviral therapy (ART) use in pregnancy. Children who are HEU are at risk of delayed neurodevelopment; however, there is limited research on early brain growth and maturation. We aimed to investigate the effects of in utero exposure to HIV/ART on brain structure of infants who are HEU compared to HIV-unexposed (HU).MethodsMagnetic resonance imaging using a T2-weighted sequence was undertaken in a subgroup of infants aged 2-6 weeks enrolled in the Drakenstein Child Health Study birth cohort, South Africa, between 2012 and 2015. Mother-child pairs received antenatal and postnatal HIV testing and ART per local guidelines. We compared subcortical and total grey matter volumes between HEU and HU groups using multivariable linear regression adjusting for infant age, sex, intracranial volume and socio-economic variables. We further assessed associations between brain volumes with maternal CD4 cell count and ART exposure.ResultsOne hundred forty-six infants (40 HEU; 106 HU) with high-resolution images were included in this analysis (mean age 3 weeks; 50.7% male). All infants who were HEU were exposed to ART (88% maternal triple ART). Infants who were HEU had smaller caudate volumes bilaterally (5.4% reduction, p < 0.05) compared to HU infants. There were no group differences in other subcortical volumes (all p > 0.2). Total grey matter volume was also reduced in infants who were HEU (2.1% reduction, p < 0.05). Exploratory analyses showed that low maternal CD4 cell count (<350 cells/mm3 ) was associated with decreased infant grey matter volumes. There was no relationship between timing of ART exposure and grey matter volumes.ConclusionsLower caudate and total grey matter volumes were found in infants who were HEU compared to HU in the first weeks of life, and maternal immunosuppression was associated with reduced volumes. These findings suggest that antenatal HIV exposure may impact early structural brain development and improved antenatal HIV management may have the potential to optimize neurodevelopmental outcomes of children who are HEU.

Dataset Information

Metabolic complications of in utero maternal HIV and antiretroviral exposure in HIV-exposed infants.

Publications

Metabolic complications of in utero maternal HIV and antiretroviral exposure in HIV-exposed infants.

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