Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects.

Introduction: The unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk-benefit messaging when a safety signal is identified.

Discussion: The Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll-out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk.

Syphilis in HIV-infected mothers and infants: results from the NICHD/HPTN 040 study.

Background: Untreated syphilis during pregnancy is associated with spontaneous abortion, stillbirth, prematurity and infant mortality. Syphilis may facilitate HIV transmission, which is especially concerning in low- and middle-income countries where both diseases are common.

Methods: We performed an analysis of data available from NICHD/HPTN 040 (P1043), a study focused on the prevention of intrapartum HIV transmission to 1684 infants born to 1664 untreated HIV-infected women.

Infant growth outcomes after maternal tenofovir disoproxil fumarate use during pregnancy.

Objective: To determine whether maternal use of tenofovir disoproxil fumarate for treatment of HIV in pregnancy predicts fetal and infant growth.

Methods: The study population included HIV-uninfected live-born singleton infants of mothers enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 (born 2002-2011) in the United States and exposed in utero to a combined (triple or more) antiretroviral regimen. Infant weight at birth and 6 months was compared between infants exposed and unexposed to tenofovir in utero using 2-sample t test, χ test, and multivariable linear and logistic regression models, including demographic and maternal characteristics.

Lipids and lactate in human immunodeficiency virus-1 infected pregnancies with or without protease inhibitor-based therapy.

Objective: To evaluate the effect of protease inhibitors on lipid and lactate levels and gastrointestinal symptoms in pregnancy.

Methods: Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (ACTG) A5084 was an observational cohort study of human immunodeficiency virus (HIV)-infected pregnant women. Women recruited between 20 and 34 weeks of gestation were required to be on a stable, highly active antiretroviral therapy (HAART) regimen, stratified by protease inhibitor compared with no protease inhibitor regimens.