Surveillance Monitoring for ART Toxicities (SMARTT) Study

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Project Summary/Abstract The Surveillance Monitoring for ART Toxicities (SMARTT) study was developed by the Pediatric HIV/AIDS Cohort Study (PHACS) network to evaluate the safety of in utero antiretroviral (ARV) exposures on children born to mothers with HIV. The study has been highly productive, informing national and international guidelines for safe and effective ARV regimens during pregnancy. The SMARTT study uses an innovative trigger-based surveillance approach for identifying adverse events (AEs) that may be attributed to prenatal and perinatal ARV therapy exposure. All children receive periodic clinical and laboratory evaluations and only those meeting certain thresholds or “triggers” receive additional assessments to evaluate specific AE criteria designated as “cases”. The study opened to enrollment in 2007, and as of October 2019 has enrolled over 4000 infants and children who are HIV-exposed but uninfected (CHEU) born to mothers with HIV. By 2019, 33% of children had met case status in at least one domain. Pregnant women living with HIV are increasingly receiving combination antiretroviral treatment at the time of conception, and newer ARV medications approved over the last decade have raised concerns regarding possible increased risk of congenital anomalies, preterm birth, and other adverse birth outcomes. As the landscape of treating HIV in pregnancy evolves, there is a need to develop the most cost-effective and informative study designs for future monitoring of ARV safety among CHEU. Building on the established experience of the PHACS network, we will enroll 200 mother-infant pairs over 5 years from 21 clinical sites to evaluate potential adverse birth outcomes and alterations in growth and neurodevelopment, and cardiometabolic, maternal, and oral health based on follow-up from birth through age 5 (intensive follow-up cohort). We will also conduct targeted long-term follow-up through age 17 years among CHEU identified as AE cases based on the SMARTT trigger design, along with a comparison cohort of 800 randomly-selected CHEU (stratified by clinical research site), to evaluate persistence, resolution, and longitudinal profiles of health functioning across multiples domains of interest (extended follow-up cohort). This large cohort will serve as a platform for multiple separately funded emerging research pilots, and allow synergy with other PHACS projects. Innovative epidemiologic and statistical methods will be used to analyze this large dataset to promote improved understanding of both child and maternal health in relation to HIV.