Researchers at Harvard School of Public Health (HSPH) have been awarded a $30 million five-year grant to study the long-term effects on children of antiretroviral (ART) drugs that were administered to their pregnant mothers in an effort to prevent mother-to-infant transmission of HIV.
The award is from the National Institute of Child Health and Human Development of the National Institutes of Health (NIH). It will establish the Pediatric HIV/AIDS Cohort Study (PHACS) to evaluate the growth and development of two cohorts of children to be called the Surveillance Monitoring for ART Toxicities Study and the Adolescent Master Protocol.
Data will come from patients enrolled and followed in previous studies as well as new children currently in care at clinical sites in the United States. Clinical sites, in which HIV care, including the provision of antiretroviral therapy is the standard of care, will be selected during the next year.
The scientific objectives of the Surveillance Monitoring for ART Toxicities Study (SMART Study) will be to evaluate the long-term safety of ART used to prevent mother-to-infant transmission of HIV-1 among 2,000 uninfected children, including potential toxicities arising from damage to mitochondrial DNA.
A second cohort, the Adolescent Master Protocol, is designed to evaluate the impact of HIV infection and ART on growth and development, sexual maturation, pubertal development, and cognitive, academic, vocational, and social functioning of 1,000 pre-adolescents and adolescents with perinatal HIV as they proceed through adolescence into adulthood.
The principal investigator for the PHACS data and operations center awarded to HSPH is George Seage, associate professor of epidemiology at HSPH. Other HSPH faculty collaborators are Paige Williams from the Center for Biostatistics and AIDS Research (CBAR) and Miguel Hernan, Sonia Hernandez-Diaz, Arnold Chan, and James Robbins from the HSPH Department of Epidemiology. HSPH is collaborating with Westat Inc., Frontier Science and Technology Research Foundation (FSTRF), and the Boston University School of Public Health. Russell Van Dyke, of Tulane University School of Medicine, will head the PHACS scientific coordinating center that includes Seage and other HSPH faculty.ÝÝ
“It is suspected that while ART therapy saves the lives of thousands of children born to HIV-positive mothers, these strong medications may have some long-term safety concerns,” said HSPH’s Seage. “We hope that by closely analyzing health indicators among HIV- and ART-exposed children, we can suggest to clinicians how to adjust therapy or step in with remedial interventions to minimize any aftereffects of life-saving treatment.”
Seage continued, “Also the health and social well-being of HIV-positive, perinatally infected preadolescents and adolescents has only been minimally examined because until the advent of successful ART treatment there were so few of them. We need to know more about the impact of HIV and lifelong ART on their sexual maturation, pubertal development, and socialization as they grow into adolescence.”
PHACS is an observational prospective cohort study and will collect data on children and adolescents already in care. HSPH will be analyzing data obtained from these sites, but will not be providing care.