In Uteroand Postnatal Exposure to Antiretrovirals Among HIV-Exposed But Uninfected Children in the United States

Abstract

An increasing number of antiretroviral agents (ARVs) are approved for use, but their use during pregnancy in the United States has not been completely described. We used data from the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring for ART Toxicities (SMARTT) study, a United States-based prospective cohort study of HIV-exposed but uninfected children, to assess temporal trends and maternal characteristics associated with the use of ARVs during pregnancy. The proportion of children exposed in utero to ARVs was calculated over time. A multivariable logistic regression model was used to estimate associations of maternal characteristics with use of highly active antiretroviral therapy (HAART) during pregnancy. We studied 1768 HIV-exposed but uninfected children born between 1995 and 2009 and enrolled in SMARTT. Prenatal HAART exposure increased from 19% in 1997 to 88% in 2009. Of children born in 2009, 99% had prenatal exposure to NRTIs (including zidovudine, 73%; lamivudine, 72%; tenofovir, 39%; and emtricitabine, 37%). Exposure to protease inhibitors increased from 15% in 1997 to 86% in 2009, while exposure to non-nucleoside reverse transcriptase inhibitors (NNRTIs) declined from 33% in 2003 to 11% in 2009. Higher maternal HIV RNA viral load (VL) concentration, lower maternal CD4 count, and earlier timing of the first maternal CD4 or VL measurement during pregnancy were associated with increased odds of HAART exposure. Prenatal HAART exposure has increased but is not universal. As ARV use during pregnancy continues to evolve, follow-up of children is needed to assess long-term effects of ARV exposures.

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

“…19 Maternal ARV use and pregnancy characteristics Start and stop dates for all ARVs taken during pregnancy were obtained via chart abstraction to classify trimester(s) and duration of exposure to each agent. 20 Combination antiretroviral therapy (cART) was defined as any regimen containing at least three ARVs from two or more drug classes. Data on income, education, smoking, and alcohol use during pregnancy were collected by interview.…”

Interactions of tenofovir and tenofovir disoproxil fumarate with drug efflux transporters ABCB1, ABCG2, and ABCC2; role in transport across the placenta

“…To improve its pharmacokinetic properties, TFV is administered in the form of disoproxil fumarate. Despite being classified as pregnancy category B drug, WHO has incorporated tenofovir disoproxil fumarate (TDF) into recent guidelines for prophylaxis of HIV MTCT [2] and its use in pregnancy tends to increase [5,6]. It must be stressed out that medication of pregnant women requires special attention to guarantee adequate and well tolerated therapy throughout gestation; among others, changes in pharmacokinetics during pregnancy [7] and quantification of drug transport across the placenta [8] need to be taken into account.…”

Long-Term Effects of In Utero Antiretroviral Exposure: Systolic and Diastolic Function in HIV-Exposed Uninfected Youth

“…6 Data on self-reported substance use during pregnancy, including smoking, alcohol, and illicit drug use (e.g., marijuana, cocaine, opiates), were collected by interview. The latest maternal CD4+ lymphocyte counts and percentages and HIV RNA viral load levels available before labor and delivery were abstracted from medical records, as well as the earliest corresponding measures during pregnancy if available.…”

“…6,7 Thus, comparison of cardiac measures by HAART exposure requires careful consideration of a number of potential confounding measures. As children transition to adolescence, the home environment may exert a stronger influence on child health outcomes.…”