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Cases of mother-to-child-transmission in the Surveillance Monitoring of ART Toxicities Study of Pediatric HIV/AIDS Cohort Study were identified from 2007 to 2015. Among 2123 births, 9 infants were HIV infected, giving a mother-to-child-transmission rate of 0.5% (95% confidence interval: 0.3%-1.0%). Mothers with perinatal HIV infections had a higher mother-to-child-transmission rate (1.1%; 95% confidence interval: 0.3%-4.3%) than mothers without perinatal HIV infections (0.4%; 95% confidence interval: 0.2%-1.0%), associated with a greater likelihood of detectable viral load at delivery.

Background:Abnormal childhood growth may affect future health. Maternal tenofovir (TFV) use was associated with lower body length and head circumference at 1 year of age in HIV-exposed uninfected (HEU) US children.Methods:We studied 509 HEU children in the US-based Surveillance Monitoring of Antiret

Maternal tenofovir disoproxil fumarate (TDF) treatment among HIV-infected pregnant women results in fetal tenofovir (TFV) exposure. Fetal TFV toxicity was demonstrated in animals, but most clinical investigations have not observed toxicity in humans.We evaluated HIV-exposed, uninfected infants in the Surveillance Monitoring for Antiretroviral Therapy Toxicities cohort of the Pediatric HIV/AIDS Cohort Study whose mothers were prescribed TDF for ≥ 8 third trimester weeks. Infant dual-energy X-ray absorptiometry scans were obtained at 0-4 weeks to measure whole body bone mineral content. Meconium TFV concentrations were quantified by liquid chromatography-tandem mass spectrometry.Fifty-eight TFV-exposed infants had meconium TFV quantified. Detectable concentrations were 11-48,100 ng/g; 3 infants had undetectable concentrations. Maternal TDF prescription duration ranged from 8 to 41 gestational weeks; infant gestational ages were 36-41 weeks. Meconium TFV concentrations were not correlated with TFV exposure duration or timing and did not vary by concomitant prescription of protease inhibitors. Increased meconium TFV concentrations were associated with greater gestational ages (ρ = 0.29, P = 0.03) and lower maternal plasma HIV RNA before delivery (ρ = -0.29, P = 0.04). Meconium TFV concentrations were not associated with infant weight, length (n = 58) or bone mineral content (n = 49).For the first time, we explored associations between meconium TFV concentrations and infant growth and bone measurements; we did not observe a meconium concentration-dependent relationship for these infant outcomes. These findings support other clinical research failing to show dose-response relationships for growth and bone outcomes among intrauterine TFV-exposed infants. High meconium TFV concentrations correlated with low maternal viral load, suggesting maternal TDF adherence significantly contributes to meconium TFV concentrations.

Use of antiretroviral (ARV) medications during pregnancy has led to a dramatic decline in mother-to-child transmission of human immunodeficiency virus (HIV)1 while increasing the number of HIV-exposed, uninfected children worldwide.2,3 ARVs may have a negative effect on infant and child health and development.2,4-6 Currently, most pregnant women with HIV in the U.S. receive combination ARV (cARV) therapy to prevent mother-to-child transmission.2,4,7-9 Investigators conducting human and animal studies of prenatal ARV exposure have noted structural and functional changes in the central nervous system (CNS),10-13 suggesting the CNS may be an important target of these agents. In utero exposure to NRTIs such as zidovudine (Retrovir; GlaxoSmithKline, Brentford, Middlesex, UK) has been associated with mitochondrial toxicities in animal and human studies.14-23 Mitochondrial defects adversely affect high-energy organ systems including the brain and peripheral nervous system.24 Conflicting information exists regarding effects of ARV exposure on neurologic and neurodevelopmental functioning. The French Perinatal Cohort study25 examined approximately 1800 children exposed to ARVs and reported 8 with findings compatible with mitochondrial dysfunction, higher than expected in the general population. The European Collaborative Study26 and the Petra study27 found no increase in the rate of severe adverse events in children with perinatal ARV exposure. Among 1037 HIV-exposed, uninfected children, Brogly and colleagues28 identified 20 (1.9%) with possible mitochondrial dysfunction, including 19 with neurological or developmental abnormalities. No clear-cut association with in utero NRTI exposure emerged, but results suggested that first exposure to lamivudine (Epivir; GlaxoSmithKline, Brentford, Middlesex, UK) or zidovudine/lamivudine (Combivir; GlaxoSmithKline, Brentford, Middlesex, UK) in third trimester might be associated with clinical findings of mitochondrial dysfunction. Children with clinical abnormalities in this study tended to have laboratory evidence of mitochondrial abnormalities compared to ARV-exposed and ARV-unexposed children without clinical findings.29 A risk-benefit analysis of ARV use in pregnancy30 found the three least effective regimens demonstrated low toxicity, while three-drug ARV regimens initiated in first trimester resulted in fewer HIV infections but slightly more cases of suspected mitochondrial toxicity. Risk for lowered cognitive performance or increased behavior problems in ARV- and HIV-exposed children is not firmly established.31-35 The French Perinatal Cohort study25 found evidence of developmental delay in children with prenatal ARV exposure, but other investigators26,27,31,32 reported no such association. Some studies did not control adequately for maternal/caregiver and environmental characteristics associated with developmental delays in infants and children, including prenatal exposure to alcohol, drugs, and infections; environmental factors such as poverty, lead exposure, maternal education, and parental medical and psychiatric illness; and, for infants with HIV exposure, severity of maternal HIV disease and pre- and postnatal ARV exposure.28,30,36-41 The primary objective of this analysis was to evaluate safety of in utero and neonatal ARV exposure with respect to development in HIV-exposed, uninfected infants during the first year of life. Specific aims were: (1) describe infant development across developmental domains, (2) evaluate prenatal and postnatal factors confounding the relationship between in utero ARV exposure and infant development, (3) evaluate effects of type and timing of prenatal ARV exposure on development, and (4) evaluate effects of neonatal ARV exposure on development.

Elevated aspartate aminotransferase-to-platelet ratio index (APRI) may signal liver fibrosis. Among 397 US children with perinatal HIV infection, APRI at baseline was > 1.5 in 0.8% (95% confidence interval [CI], 0.2–2.2%) and > 0.5 in 6.5% (95%CI, 4.3–9.4%); incidence on study was 0.5 (95%CI, 0.2–1.2) and 6.4 (95%CI, 4.8–8.3) per 100 person-years, respectively. Long-term liver outcomes after perinatal HIV infection warrant further study.

Background: Some studies have detected associations between in utero antiretroviral therapy (ARV) exposure and birth defects but evidence is inconclusive. Methods: A total of 2202 human immunodeficiency virus (HIV)-exposed children enrolled in the Pediatric AIDS Clinical Trials Group 219 and 219 C protocols before 1 year of age were included. Birth defects were classified using the Metropolitan Atlanta Congenital Defects Program coding. Logistic regression models were used to evaluate associations between first trimester in utero ARV exposure and birth defects. Results: A total of 117 live-born children had birth defects for a prevalence of 5.3% (95% confidence interval [CI] : 4.4, 6.3). Prevalence did not differ by HIV infection status or overall ARV exposure; rates were 4.8% (95% CI: 3.7, 6.1) and 5.8% (95% CI: 4.2, 7.8) in children without and with first trimester ARV exposure, respectively. The defect rate was higher among children with first trimester efavirenz exposure (5/32, 15.6%) versus children without first trimester efavirenz exposure (adjusted odds ratio [aOR] = 4.31 [95% CI: 1.56, 11.86]). Protective effects of first trimester zidovudine exposure on musculoskeletal defects were detected (aOR = 0.24 [95% CI: 0.08, 0.69]), while a higher risk of heart defects was found (aOR = 2.04 [95% CI: 1.03, 4.05]). Conclusions: The prevalence of birth defects was higher in this cohort of HIV-exposed children than in other pediatric cohorts. There was no association with overall ARV exposure, but there were some associations with specific agents, including efavirenz. Additional studies are needed to rule out confounding and to evaluate newer ARV agents.