Safety of tenofovir use during pregnancy

Abstract

Objective To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants. Design US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure. Methods We evaluated the association of maternal TDF use during pregnancy with small for gestational age (SGA); low birth weight (LBW, <2.5kg); weight-for-age z-scores (WAZ), length-forage z-scores (LAZ) and head circumference-for-age (HCAZ) z-scores at newborn visit; and LAZ, HCAZ, and WAZ at age one year. Logistic regression models for LBW and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted linear regression models were used to evaluate LAZ, WAZ and HCAZ by TDF exposure. Results Of 2029 enrolled children with maternal antiretroviral information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14% in 2003 to 43% in 2010. There was no difference between those exposed to combination regimens with versus without TDF for SGA, LBW, and newborn LAZ and HCAZ. However, at age one year, infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: −0.17 vs. −0.03, p=0.04; HCAZ: 0.17 vs. 0.42, p=0.02). Conclusions TDF use during pregnancy was not associated with increased risk for LBW or SGA. The slightly lower mean LAZ and HCAZ observed at age one year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy.

Tenofovir exposure in utero and linear growth in HIV-exposed, uninfected infants

“…Over time, substantial changes have occurred in prescribing patterns resulting in highly heterogeneous ART exposure, making it difficult to single out the effects of a single drug whilst also increasing the risk for confounding by indication. [3, 4] In particular, the use of TDF with a PI has generally been more common in the US than in African settings including ours,[16, 18, 19] and residual confounding may explain some of the differences observed in observational studies. Differences in co-occurring risk factors for poor child growth may however also contribute to the differential results.…”

“…In a large US cohort, the average length-for-age Z-score (LAZ) for 12-month old HEU infants exposed to TDF-containing ART regimens in utero was 0.14 lower than for those without TDF exposure. [3] In a similar but smaller cohort, TDF-exposed neonates had demonstrably lower bone mineral content (BMC) than their unexposed counterparts. [4] By contrast, preliminary data from the randomized IMPAACT-PROMISE trial conducted in Malawi, Zimbabwe, Uganda and South Africa showed no adverse association between TDF exposure and either birth length or neonatal BMC, although triple ART-exposed infants as a group had lower BMC than those exposed only to short course antiretrovirals for PMTCT.…”

Adverse drug reactions associated with antiretroviral therapy during pregnancy

“…In the APR, the prevalence of overall birth defects with exposure to TDF in the first trimester was 2.4% of 1612 live births and did not differ from the background rate in the USA [148]. Two studies showed no difference in fetal growth between infants exposed or not exposed to TDF [160,161]. TDF has limited penetration into breast milk, which limits its potential toxicity to the breastfeeding infant.…”

It is Time to Explore the Potential Benefit of Routine Micronutrient Supplementation in Optimizing Bone Health and Growth in HIV Exposed Uninfected Children in the Context of Early Antiretroviral Exposure in Resource Limited Settings

“…Additionally, children born to HIV infected women are already prone to undernutrition related to maternal factors yet nutrition plays a critical role in bone mass formation and mineralization during the fetal and infancy periods, 13,14 Some studies have indicated lower Bone Mineral Content (BMC) and lower height-for-age Z-score (HAZ) as well as lower head circumference-for-age Z-score (HCAZ) in infants exposed to TDF in-utero. [15][16][17] More recently, a study that was designed to evaluate the potential bone and kidney toxic effects of TDF among HIVinfected pregnant and breastfeeding women and their infants reported that there were significant decreases in BMC among newborns whose mothers received Protease Inhibitor-based ART during pregnancy compared to those who received only zidovudine (ZDV) during pregnancy. 18 Another first line antiretroviral, EFV is associated with vitamin D deficiency through multiple postulated mechanisms.…”