An International Prospective Cohort Study of HIV and Zika in Infants and Pregnancy (HIV ZIP): Study Protocol.

Ann Aschengrau,Frances Whalen,Jill Lebov,Dina Monte,Patricia A Garvie,John Moye,Paige L Williams,Nahida Chakhtoura,Brad Karalius,Kunjal Patel,George R Seage,Marisa M Mussi-Pinhata

doi:10.3389/fgwh.2021.574327

Abstract

Zika virus (ZIKV) infection may adversely affect pregnancies of women living with HIV (WLHIV). Because no study to date has focused on maternal and child effects of HIV and ZIKV co-infection in pregnant women, we undertook the International Prospective Cohort Study of HIV and Zika in Infants and Pregnancy (HIV ZIP). The aims of this two-phase study of pregnant women and their infants are to compare the incidence of ZIKV infection among pregnant women with and without HIV infection and to determine the risk of adverse maternal and child outcomes associated with ZIKV/HIV co-infection at clinical sites in Brazil, Puerto Rico, and the continental United States. Phase I was designed to enroll pregnant women/infant pairs who were: (1) infected with HIV only, (2) infected with ZIKV only, (3) infected with HIV and ZIKV, and (4) not infected with either HIV or ZIKV. A key goal of this phase was to assess the feasibility of enrolling 200 women/infant pairs within a year, with a target of 150 WLHIV, 50 HIV-uninfected women, and a minimum of 20 who were co-infected with HIV and ZIKV. If the feasibility of Phase I proved successful, Phase II would enroll up to 1,800 additional pregnant women/infant pairs to the same four groups. Enrolled women in both phases were to be followed throughout their pregnancy and up to 6 weeks post-partum. Infants were also to be followed for 1 year after birth. To date, Phase 1 data collection and follow-up have been completed. Delineation of possible harmful effects of HIV/ZIKV co-infection will allow the formulation of standard-of-care recommendations to minimize adverse effects but enable the continuation of preventive HIV therapy. Furthermore, while the prospective HIV ZIP study was developed before the COVID pandemic, it is especially relevant today since it can be easily adapted to provide critically important information on the impact of COVID-19 infection or other still unrecognized new agents among pregnant women and their offspring worldwide.

Highlights

Zika virus (ZIKV) infection may adversely affect pregnancies of women living with HIV (WLHIV)
The HIV and Zika in Infants and Pregnancy (HIV Zika in Infants and Pregnancy (ZIP)) Study is a two-phase international prospective cohort study of pregnant women and their infants whose goals are to compare the incidence of ZIKV infection among pregnant women with and without HIV infection, and to determine the risk of adverse maternal and child outcomes associated with ZIKV/HIV co-infection at clinical sites in Brazil, Puerto Rico, and the continental U.S
For Aim 2 of Phase 2, we provide the minimum detectable odds ratios (ORs) at 80% power in Table 2 for comparing the percent with ZIKV infection by the end of pregnancy between WLHIV and HIV-uninfected women, based on a final target enrollment of 2,000 women, and assuming the percent with HIV infection among those enrolled is 40% (ORs are similar for percent with HIV infection ranging from 35 to 65%)

Summary

INTRODUCTION

Zika virus (ZIKV) infection may adversely affect pregnancies of women living with HIV (WLHIV). Two large cohorts from the U.S [13, 14] and one from French territories in the Americas [15] reported smaller estimates (5–7%) of pregnancy losses and/or birth defects potentially related to ZIKV in newborns of symptomatic women. It is likely that the immune system dysfunction of HIVinfected pregnant women will potentially be enhanced by acute viral infection, even in the presence of ART, increasing the risk of MTCT of both HIV and ZIKV and their consequences. There is a growing number of significant adverse infant outcomes, those related to the CNS, following prenatal ZIKV infection [36], and because HIV is a neurotropic virus, the ability of a pregnant WLHIV to maintain HIV RNA suppression will be critical for her child’s health. As we are currently experiencing another widespread pandemic stemming from COVID-19 [38], the need for rapid deployment of studies with adaptable protocols is even more urgent

Study Design and Setting

DISCUSSION

Findings

ETHICS STATEMENT