FEASIBILITY STUDY OF A PROSPECTIVE COHORT OF HIV & ZIKA IN INFANTS AND PREGNANCY (HIV-ZIP)

Westat, Inc., Rockville MD

Investigators

Abstract

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) seeks to establish an Indefinite-delivery, Indefinite-quantity (IDIQ) Task Order (TO) Contract to support clinical activities for international and domestic pediatric and maternal HIV and other high priority infectious diseases. Individual Task Orders awarded will be warded during this five-year ordering period. The ordering period is 12/1/2017-11/30/2022. NICHD provides clinical trial sites to some other clinical trial networks such as the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) The IMPAACT network and its leadership group are in charge of the creation of all their studies, protocols, and clinical trials. These activities are funded through Grants/Cooperative agreements sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The IMPAACT Network is a cooperative group of institutions, investigators, and other collaborators mainly focused on evaluating potential therapies for HIV infection and its related symptoms and co-infections in infants, children, adolescents and pregnant women. This includes clinical trials of HIV/AIDS interventions for the prevention of mother to child transmission. In 1990 the NICHD began collaborating with the Pediatric AIDS Clinical Trials Group, (PACTG) to expand clinical trial availability at NICHD clinical trial centers/sites. This collaboration made possible to conduct clinical trials by the IMPAACT Network to further evaluate antiretroviral therapeutic agents, other therapies targeted at opportunistic infections, and interventions to prevent perinatal HIV transmission. In recent years, the collaboration is expanding to evaluate potential HIV cure approaches and vaccines. The NICHD will continue providing this Coordinating Center Contract support to the IMPAACT Network providing access to sites and the clinical populations of interest. Zika virus (ZIKV) is an arbovirus (vector-borne virus) of the genus Flaviviridae. Until recently, infections with ZIKV were thought to be mild and self-limiting. Since 2015 however, ZIKV infections have been associated with an increase in microcephaly and other birth defects in newborns following infection of the mother during pregnancy. More recently, it has been associated with Guillain-Barré Syndrome (GBS) in adults of both sexes. Another virus, the Human Immunodeficiency Virus (HIV), is the cause of Acquired Immunodeficiency Syndrome (AIDS), and likewise causes perinatal or congenital infection. Despite substantial progress in reducing maternal to child transmission (MTCT) of HIV, there still were more than 830,000 HIV infected pregnant women identified worldwide in 2015 by screening provided through the President?s Emergency Program for AIDS Relief (PEPFAR), and approximately 8,500 HIV-infected pregnant women give birth each year in the United States. maternal health Objectives This is a feasibility study of a prospective international cohort of pregnant women and their infants from those pregnancies. Its goals are to evaluate the feasibility of a comparative study of the incidence of Zika virus (ZIKV) infection among pregnant women with and without Human Immunodeficiency Virus (HIV) infection and to determine the risk of adverse outcomes associated with ZIKV/HIV co-infection across clinical sites in the continental United States (U.S.), Puerto Rico (P.R.), and Brazil. The study will (1) determine the feasibility of satisfactorily achieving accrual targets and (2) confirm the adequacy of statistical assumptions for power and sample size considerations for a future large scale study in this patient population, as well as (3) provide adequate statistical power to detect clinical meaningful differences in the proportions of HIV-infected women with unsuppressed HIV viral load between HIV-infected women with Zika and HIV-infected women without Zika infection, assuming 10% of the HIV-infected women enrolled (and meeting Zika risk criteria) have ZIKV infection by delivery (maternal health). The primary study analysis will produce a report that addresses each of the topics enumerated above. Specifically, the Contractor shall carry out the following tasks. 1. The Contractor shall identify, recruit, screen, enroll within one year, and conduct protocol specified study evaluations in up to 200 pregnant women pairs who are: (1) infected with HIV only; (2) infected with ZIKV only; (3) infected with HIV and ZIKV; and (4) not infected with HIV or ZIKV. The recruitment will target 150 HIV-infected women, 50 HIV-uninfected women from the continental U.S. sites only, and a minimum of 20 who are co-infected with HIV and ZIKV. The Contractor shall test all HIV-infected and uninfected study participants for ZIKV. The Contractor shall follow enrolled women and their infants throughout pregnancy and through six weeks postpartum. 2. The contractor will coordinate the overall conduct of the study in an effective and efficient manner, to include responsibility for assuring operation and monitoring of the selected clinical sites where study participants are identified, enrolled, and evaluated. 3. The Contractor shall provide personnel, facilities, and other services necessary to maintain and coordinate the conduct of the HIV-ZIP study.