Clinical trial NCT03263195: Prospective Cohort Study of HIV and Zika in Infants and Pregnancy
Official title: Prospective Cohort Study of HIV and Zika in Infants and Pregnancy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
Zika Virus
Pregnant Women
Keywords: HIV
Zika Virus
Pregnancy
MTCT
Lead sponsor: Westat
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2017-08-28
Enrollment: 395
Sex: FEMALE
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

Detailed description: This is a two-phase prospective international cohort study of pregnant women and their infants from those pregnancies 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 across clinical sites in the continental U.S., P.R. and Brazil.

Phase I will enroll pregnant women/infant 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. Phase I will assess the feasibility of enrolling a total of 200 pregnant women/infant pairs within a year, with a target of 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 by the end of pregnancy.

Should the feasibility of Phase I prove successful, Phase II will commence by enrolling up to 1,800 additional pregnant women/infant pairs to the 4 groups described above. The comparison group of HIV-uninfected pregnant women/infant pairs from P.R and Brazil (ZIKV-infected and uninfected) will be obtained from data collected in the concurrent International Prospective Observational Cohort Study of Zika in Infants and Pregnancy (ZIP study).

All HIV-infected and uninfected study participants will be tested for ZIKV. Enrolled women will be followed throughout their pregnancy and up to six weeks postpartum. Infants born to enrolled women will be followed for a full year after birth. Thereafter, the infants born to women at continental U.S. and P.R. sites also implementing the Surveillance Monitoring for Antiretroviral Therapy (ART) Toxicities (SMARTT) study may be followed up yearly until adulthood through SMARTT depending on the availability of funds.

Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

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.

Primary outcomes:
measure: 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).
timeFrame: At the time of delivery of all those enrolled up to 1 year after the first enrollment
measure: Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery.
timeFrame: Maternal viral load at delivery
measure: Incidence of ZIKV Infection (Among Pregnant Women With HIV Infection Compared to Those Without HIV Infection).
timeFrame: Maternal baseline to delivery
measure: 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).
timeFrame: At time of delivery
measure: 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).
timeFrame: Infant birth to 12 months
measure: 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).
timeFrame: Infant birth, 3 months
measure: Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone.
timeFrame: Infant birth to 12 months
measure: Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV
timeFrame: Infant Birth, 3 months, 6 months, 12 months
measure: Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV
timeFrame: Infant Birth, 3 months, 6 months, 12 months
measure: Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV
timeFrame: Within one month of infant birth, 3 months, 6 months, 12 months
measure: Ophthalmologic Structure and Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV
timeFrame: Within one month of infant birth, 12 months;
measure: Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV
timeFrame: Infant 3 months, 6 months, 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Pediatric/Prenatal HIV/AIDS
state: Florida
city: Bronx
country: United States
facility: Bronx-Lebanon Hospital Center NICHD CRS
state: New York
city: Houston
country: United States
facility: Baylor College of Medicine; Texas Children's Hospital
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Belo Horizonte
country: Brazil
facility: SOM Federal University Minas Gerais Brazil NICHD CRS
state: Minas Gerais
city: Rio de Janeiro
country: Brazil
facility: Hospital Federal dos Servidores do Estado NICHD CRS
city: Rio de Janeiro
country: Brazil
facility: Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS
city: Rio de Janeiro
country: Brazil
facility: Hosp. Geral De Nova Igaucu Brazil NICHD CRS
city: São Paulo
country: Brazil
facility: University of Sao Paulo at Riberaio Preto Brazil
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico Pediatrics HIV/AIDS Research Program
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
Study officials:
affiliation: University of Sao Paolo, Riberao Preto Medical School, Department of Pediatrics
name: Marisa M. Mussi-Pinhata, MD
role: STUDY_CHAIR
References: