Project Summary/Abstract Zika virus (ZIKV) is likely to become endemic and pose a sustained threat to pregnant women in areas where human immunodeficiency virus (HIV) infection is also common. This concern motivated the NIH to initiate ‘Prospective Cohort Study of HIV and Zika in Infants and Pregnancy’ (HIV ZIP) -- an international, 4-6 year, 2,000 person clinical study to examine the impact of HIV/ZIKV co-infections on pregnant women and their infants. The purpose of this grant is to complement HIV ZIP by rapidly obtaining companion data from highly controlled studies of macaque monkeys. Specifically, we will: Aim 1: Evaluate adverse pregnancy outcomes in rhesus macaques infected with simian immunodeficiency virus (SIV) only, ZIKV only, both SIV and ZIKV, and neither SIV nor ZIKV. As in the HIV ZIP trial, SIV-infected macaques will be virologically suppressed using antiretroviral drugs. All 24 pregnancies will be monitored carefully throughout gestation for adverse pregnancy outcomes including spontaneous miscarriage, prolonged ZIKV viremia, SIV-associated disease, and ZIKV neuropathogenesis. Aim 2: Define impacts of in utero SIV and ZIKV infections on infant growth, hearing, vision, and neurodevelopment in the first year of life. Because macaques develop more quickly than humans, abnormalities that occur by one year of age may presage future impacts in children born with congenital Zika syndrome (CZS). Aim 3: Assess incidence of vertical transmission of SIV and ZIKV. Comprehensive necropsies of newborns will be performed at one year of age and more than 60 tissues will be examined for the presence of SIV and ZIKV viral RNA, as well as negative-sense ZIKV RNA replication intermediates. This study is made possible by our large network of collaborators who have extensive experience studying both SIV and ZIKV in macaques. Data from this study will inform HIV ZIP and provide an early indication of whether babies born to HIV+ women are at enhanced risk for CZS.