Prospective Cohort Study of HIV and Zika in Infants and Pregnancy

NCT03263195 | Completed Results DMC

• 2 other identifiers: HIV-ZIPHHSN275201800001I
• Study Type: observational
• Target: 395
• Locations: 3 countries
• Sites: 11

Brief Summary

The purpose of this study is to compare 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 maternal and child outcomes associated with ZIKV/HIV co-infection across clinical sites in the continental United States (U.S.), Puerto Rico (P.R.) and Brazil.

Conditions

HIV; Zika Virus; Pregnant Women

Keywords

HIV; Zika Virus; Pregnancy; MTCT

Outcome Measures

Primary Outcomes (12)

• Enrollment (150 HIV-infected and 50 HIV-uninfected Pregnant Women Within One Year, With a Minimum of 20 of These Women Having HIV/ZIKV Co-infection by Their End of Pregnancy).

  This outcome measured feasibility of enrolling 150 pregnant women living with HIV and 50 pregnant women without HIV, with a minimum of 20 of these women having HIV/ZIKV co-infection by their end of pregnancy

  At the time of delivery of all those enrolled up to 1 year after the first enrollment

• Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery.

  This outcome intended to measure HIV suppression at the time of delivery among women living with HIV with and without ZIKV infection during pregnancy. Note there were no women with ZIKV infection in pregnancy. Viral suppression was defined at different thresholds (\<40 copies/mL, \<400 copies/mL, \<1000 copies/mL).

  Maternal viral load at delivery

• Incidence of ZIKV Infection (Among Pregnant Women With HIV Infection Compared to Those Without HIV Infection).

  Cumulative incidence of ZIKV infection during pregnancy (among pregnant women with HIV infection compared to those without HIV infection).

  Maternal baseline to delivery

• Incidence of Adverse Pregnancy Outcomes (in Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone, and Doubly Uninfected Women).

  Adverse pregnancy outcomes included miscarriage, stillbirth and preterm delivery. Note there were no women with ZIKV infection in pregnancy. Miscarriage was defined as fetal demise at \<20 weeks of gestation. Stillbirth was defined as fetal demise at ≥20 weeks of gestation. Preterm delivery was defined as delivery at \<37 weeks of gestation.

  At time of delivery

• Incidence of Vertical Transmission of HIV and/or ZIKV (in Women Co-infected With HIV and ZIKV and Women Infected With Either HIV or ZIKV Alone).

  Cumulative incidence of confirmed HIV infection among enrolled infants. Note there were no women with ZIKV infection in pregnancy so therefore no risk of transmission of ZIKV to any infants.

  Infant birth to 12 months

• Incidence of Congenital Malformations (Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone, and Doubly Uninfected Women).

  Cumulative incidence of congenital malformations. Note there were no women with ZIKV infection in pregnancy. Observed major congenital malformations included: anhydramnios, cerebral ventriculomegaly, clubfoot (unresolved), Down syndrome, hydrops, hypospadias, patient ductus arteriosus, polydactyly (left foot), Potter syndrome, short stature, syndactyly (left foot, 1st and 2nd toes). Observed minor congenital malformations included: clubfoot (resolved), cryptorchidism (bilateral), dislocated hip, heart defect (patent foramen ovale), heart murmur (unresolved), hemangioma, hip dysplasia, hydrocele, inguinal hernia, head circumference -3 ≤ z-score \<-2, persistent ductus arteriosus (resolved), plagiocephaly, restrictive ductus arteriosus, renal pyelectasis, sacral dimple, small perimembranous ventricular septal defect, stenosis of nasolacrimal duct, umbilical hernia.

  Infant birth, 3 months

• Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone.

  Other adverse outcomes included microcephaly, neonatal dealth, central nervous system (CNS) malformation, hydrops, and ocular abnormalities. Note there were no women with ZIKV infection in pregnancy. Microcephaly was defined as head circumference less than a z-score of -3 at birth or 3 month visit. Neonatal death was defined as death within 28 days of life. Observed CNS malformations included: cerebral ventriculomegaly. Ocular abnormalities included both structural and functional ophthalmologic abnormalities.

  Infant birth to 12 months

• Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV

  Weight as a measure of growth. Note there were no women with ZIKV infection in pregnancy.

  Infant Birth, 3 months, 6 months, 12 months

• Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV

  Length and head circumference as measures of growth. Note there were no women with ZIKV infection in pregnancy.

  Infant Birth, 3 months, 6 months, 12 months

• Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV

  Audiologic function as assessed by OAE test reported. Note there were no women with ZIKV infection in pregnancy.

  Within one month of infant birth, 3 months, 6 months, 12 months

• Ophthalmologic Structure and Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV

  Ocular abnormalities included both structural and functional ophthalmologic abnormalities. Note there were no women with ZIKV infection in pregnancy.

  Within one month of infant birth, 12 months;

• Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV

  Infant neurodevelopment was assessed by either the Bayley III or Ages and Stages Questionnaires- 3rd Edition. Combined results reported. Note there were no women with ZIKV infection in pregnancy.

  Infant 3 months, 6 months, 12 months

Study Arms (8)

Women with HIV only

Pregnant women with HIV infection only

Women with ZIKV only

Pregnant women with ZIKV infection only

Women with HIV and ZIKV

Pregnant women with HIV and ZIKV infection

Women without HIV or ZIKV

Pregnant women without HIV or ZIKV infection

Infants of women with HIV only

Infants of women with HIV infection during pregnancy

Infants of women with ZIKV only

Infants of women with ZIKV infection during pregnancy

Infants of women with HIV and ZIKV

Infants of women with HIV and ZIKV infection during pregnancy

Infants of women without HIV or ZIKV

Infants of women without HIV or ZIKV infection during pregnancy

Eligibility Criteria

• Age: 15 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Maternal: HIV infected or uninfected (the latter in the continental U.S only) pregnant women, ages 15 years and older, residing in a geographic area accessible to a research site in Brazil, Puerto Rico or the continental U.S., meet the ZIKV infection risk criteria and are less than 18 weeks GA or any GA if presenting with acute ZIKV-like symptoms and have confirmed ZIKV infection by positive ZIKV RNA detection at the Screening visit. Infant: All infants born to women while enrolled in this study if the parent(s)/legal guardian(s) consents for the infant's participation. Infants may be in one of the following groups: a) HIV infected only; b) ZIKV infected only; c) HIV and ZIKV infected; or d) HIV and ZIKV uninfected

You may qualify if:

• Maternal
• Provides written informed consent (IC) (or assent and parent(s)/legal guardian(s) permission, where required per state or country regulations).
• Age 15 years or older at enrollment.
• Confirmation of pregnancy by βhCG measurement in blood or urine or fetal ultrasound (US) heart tones present.
• Based on pregnancy calculator or fetal US: Confirmation of being at \<18 weeks gestational age (GA) of pregnancy or at any GA if presents with acute ZIKV-like symptoms (i.e., fever, rash, arthralgia, myalgia, pruritus, headache, eye pain, and conjunctivitis) and has laboratory-confirmed ZIKV infection by ZIKV RNA detection.
• Plans on remaining in the area of the current study site or if moving, within an area of any other study site, for the duration of her and her child's participation.
• Willingness of parent(s)/legal guardian(s) to provide written consent to enroll the infant from the current pregnancy once delivered.
• Has met one of the following three ZIKV-exposure risk categories:
• Has resided in for at least three months or traveled within the last three months to a country or United States (U.S.) territory with active, cautionary, or previously active or cautionary ZIKV transmission based on the list found at http://www.cdc.gov/zika/geo/active-countries.html; or
• Sexual partner has resided in or traveled within the last six months to a country or U.S. territory with active, cautionary, or previously active or cautionary ZIKV transmissions, or was diagnosed with ZIKV within the previous six months; or
• Household member has been diagnosed with ZIKV infection or has traveled since the woman's last menstrual period (LMP) to a country or U.S. territory with active, cautionary, or previously active or cautionary ZIKV transmission.
• For HIV-infected women only: Laboratory evidence or clinical criteria for a confirmed case of HIV infection per Centers for Disease Control and Prevention (CDC) Surveillance Case Definition for HIV, 2014 (Section 1.1.1 or Section 1.1.2) http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6303a1.htm.
• Infant
• Born to an enrolled mother.
• Parent(s)/legal guardian(s) provided written IC for his or her child to participate.

You may not qualify if:

• Maternal:
• Incarcerated or placed in detention.
• Enrolled in other clinical research (including other ZIKV research) requiring blood collection, which in combination with HIV ZIP evaluations would exceed a total blood draw volume of 50 mL in an eight-week period and/or blood collection would be required more frequently than two times per week.
• Infant:
• Enrolled in other clinical research (including other ZIKV research) requiring blood collection, which in combination with HIV ZIP evaluations, would exceed three mL per kg in an eight week period and/or blood collection would be required more frequently than two times per week.

Sponsors & Collaborators

• Westat: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (11)

University of Miami Pediatric/Prenatal HIV/AIDS

Miami, Florida, 33146, United States

Location

Bronx-Lebanon Hospital Center NICHD CRS

The Bronx, New York, 10457, United States

Location

Baylor College of Medicine; Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

SOM Federal University Minas Gerais Brazil NICHD CRS

Belo Horizonte, Minas Gerais, 30.130-100, Brazil

Location

Hospital Federal dos Servidores do Estado NICHD CRS

Rio de Janeiro, 20221-903, Brazil

Location

Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS

Rio de Janeiro, 21941-612, Brazil

Location

Hosp. Geral De Nova Igaucu Brazil NICHD CRS

Rio de Janeiro, 26030, Brazil

Location

University of Sao Paulo at Riberaio Preto Brazil

São Paulo, 14049-900, Brazil

Location

University of Puerto Rico Pediatrics HIV/AIDS Research Program

San Juan, 00936-5067, Puerto Rico

Location

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

Location

Biospecimen

Retention: SAMPLES WITH DNA

Maternal blood, maternal urine, cord blood, and placenta tissue. Infant blood and infant urine.

MeSH Terms

Conditions

Zika Virus Infection

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections

Results Point of Contact

• Title: Dr. Marisa Mussi-Pinhata
• Organization: Department of Pediatrics Ribeirão Preto Medical School

mmmpinha@fmrp.usp.br

55-16-3602-2807

Study Officials

• Marisa M. Mussi-Pinhata, MD

  University of Sao Paolo, Riberao Preto Medical School, Department of Pediatrics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2017
• First Posted: August 28, 2017
• Study Start: August 23, 2017
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: January 14, 2022
• Results First Posted: January 14, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: No later than one year after the date of acceptance for publication of the main findings from the final dataset.
• Access Criteria: A Memorandum of Understanding (MOU) about the extent and nature of the sharing as well as a data use agreement will be executed for all collaborations. The MOU will include an understanding of the control of the use of the data, publication rights and authorship rights, as well as address the human participant's confidentiality issues

Locations

PR (2); BR (5); US (4)