HIV, Pregnant Women, Zika Virus
Conditions
Keywords
HIV, Zika Virus, Pregnancy, MTCT
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.
Interventions
None listed
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
Westat
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
15 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | At the time of delivery of all those enrolled up to 1 year after the first enrollment | 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 |
| Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | Maternal viral load at 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). |
| Incidence of ZIKV Infection (Among Pregnant Women With HIV Infection Compared to Those Without HIV Infection). | Maternal baseline to delivery | Cumulative incidence of ZIKV infection during pregnancy (among pregnant women with HIV infection compared to those without HIV infection). |
| 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). | At time of delivery | 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. |
| 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). | Infant birth to 12 months | 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. |
| 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). | Infant birth, 3 months | 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. |
| Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Infant birth to 12 months | 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. |
| Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Infant Birth, 3 months, 6 months, 12 months | Weight as a measure of growth. Note there were no women with ZIKV infection in pregnancy. |
| Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Infant Birth, 3 months, 6 months, 12 months | Length and head circumference as measures of growth. Note there were no women with ZIKV infection in pregnancy. |
| Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Within one month of infant birth, 3 months, 6 months, 12 months | Audiologic function as assessed by OAE test reported. Note there were no women with ZIKV infection in pregnancy. |
| Ophthalmologic Structure and Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Within one month of infant birth, 12 months; | Ocular abnormalities included both structural and functional ophthalmologic abnormalities. Note there were no women with ZIKV infection in pregnancy. |
| Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Infant 3 months, 6 months, 12 months | 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. |
Countries
Brazil, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Women With HIV Only Pregnant women with HIV infection only | 174 |
| Women With ZIKV Only Pregnant women with ZIKV infection only | 0 |
| Women With HIV and ZIKV Pregnant women with HIV and ZIKV infection | 0 |
| Women Without HIV or ZIKV Pregnant women without HIV or ZIKV infection | 26 |
| Total | 200 |
Baseline characteristics
| Characteristic | Total | Women With HIV Only | Women Without HIV or ZIKV | Women With HIV and ZIKV | Women With ZIKV Only |
|---|---|---|---|---|---|
| Age, Continuous | 28.3 years | 28.2 years | 29.2 years | — | — |
| Gestational age at enrollment | 15.0 weeks | 14.5 weeks | 16.0 weeks | — | — |
| Race/Ethnicity, Customized Amarela/Yellow (Brazil) | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian (US) | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black (Brazil) | 40 Participants | 40 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black (US) | 8 Participants | 2 Participants | 6 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Indigenous (Brazil) | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed Black (Brazil) | 51 Participants | 51 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized More than one race (Brazil) | 21 Participants | 21 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized More than one race (US) | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Mulatto (Brazil) | 8 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not reported (US) | 10 Participants | 3 Participants | 7 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other (US) | 3 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White (Brazil) | 39 Participants | 39 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White (US) | 10 Participants | 4 Participants | 6 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Brazil | 164 participants | 164 participants | 0 participants | — | — |
| Region of Enrollment Puerto Rico | 9 participants | 9 participants | 0 participants | — | — |
| Region of Enrollment United States | 27 participants | 1 participants | 26 participants | — | — |
| Sex: Female, Male Female | 200 Participants | 174 Participants | 26 Participants | — | — |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | — | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 174 | 0 / 0 | 0 / 0 | 0 / 26 | 2 / 170 | 0 / 0 | 0 / 0 | 0 / 25 |
| other Total, other adverse events | 0 / 174 | 0 / 0 | 0 / 0 | 0 / 26 | 0 / 170 | 0 / 0 | 0 / 0 | 0 / 25 |
| serious Total, serious adverse events | 0 / 174 | 0 / 0 | 0 / 0 | 0 / 26 | 0 / 170 | 0 / 0 | 0 / 0 | 0 / 25 |
Outcome results
Primary
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.
Time frame: Within one month of infant birth, 3 months, 6 months, 12 months
Population: Infants enrolled in HIV ZIP
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (3 months) | Test result not available | 60 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (Birth) | Test result not available | 46 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (6 months) | Failed | 21 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (12 months) | Test result not available | 66 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (6 months) | Failed | 20 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (Birth) | Passed | 108 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (6 months) | Passed | 102 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (Birth) | Failed | 16 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (6 months) | Test result not available | 47 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (3 months) | Passed | 100 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (Birth) | Passed | 112 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (3 months) | Failed | 10 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (6 months) | Test result not available | 47 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (3 months) | Test result not available | 60 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (Birth) | Failed | 12 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (6 months) | Passed | 103 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (12 months) | Passed | 84 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (3 months) | Passed | 99 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (12 months) | Passed | 84 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (3 months) | Failed | 11 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (12 months) | Failed | 21 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (12 months) | Failed | 20 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (12 months) | Test result not available | 65 Participants |
| Women With HIV Only | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (Birth) | Test result not available | 46 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (12 months) | Test result not available | 10 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (Birth) | Test result not available | 22 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (3 months) | Test result not available | 7 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (6 months) | Passed | 14 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (6 months) | Failed | 1 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (12 months) | Passed | 13 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (Birth) | Test result not available | 22 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (6 months) | Failed | 1 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (Birth) | Passed | 3 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (Birth) | Failed | 0 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (3 months) | Passed | 17 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (3 months) | Failed | 1 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (6 months) | Test result not available | 10 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (12 months) | Failed | 2 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Right ear (12 months) | Test result not available | 10 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (Birth) | Passed | 3 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (Birth) | Failed | 0 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (3 months) | Passed | 17 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (3 months) | Failed | 1 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (3 months) | Test result not available | 7 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (6 months) | Passed | 14 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (6 months) | Test result not available | 10 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (12 months) | Passed | 13 Participants |
| Women Without HIV or ZIKV | Audiologic Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Left ear (12 months) | Failed | 2 Participants |
Primary
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
Time frame: At the time of delivery of all those enrolled up to 1 year after the first enrollment
Population: While the protocol was successful at enrolling at least 150 women living with HIV, it did not achieve its aim of enrolling 50 women without HIV and there were no ZIKV infections observed during the study period. Total enrollment into the expected arms is presented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Women With HIV Only | 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). | 174 Participants |
| Women With ZIKV Only | 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). | 0 Participants |
| Women With HIV and ZIKV | 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). | 0 Participants |
| Women Without HIV or ZIKV | 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). | 26 Participants |
Primary
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.
Time frame: At time of delivery
Population: Women enrolled in HIV ZIP during pregnancy~Miscarriage was defined as fetal demise \<20 weeks of gestation. Stillbirth was defined as fetal demise ≥20 weeks of gestation. Preterm delivery was defined as delivery at \<37 weeks of gestation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Women With HIV Only | 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). | Miscarriage | 3 Participants |
| Women With HIV Only | 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). | Stillbirth | 1 Participants |
| Women With HIV Only | 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). | Preterm delivery | 16 Participants |
| Women Without HIV or ZIKV | 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). | Preterm delivery | 1 Participants |
| Women Without HIV or ZIKV | 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). | Miscarriage | 0 Participants |
| Women Without HIV or ZIKV | 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). | Stillbirth | 0 Participants |
Primary
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.
Time frame: Infant birth, 3 months
Population: Infants enrolled in HIV ZIP
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Women With HIV Only | 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). | Major malformations | 6 Participants |
| Women With HIV Only | 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). | Minor malformations | 32 Participants |
| Women Without HIV or ZIKV | 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). | Minor malformations | 5 Participants |
| Women Without HIV or ZIKV | 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). | Major malformations | 2 Participants |
Primary
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.
Time frame: Infant birth to 12 months
Population: Infants enrolled in HIV ZIP
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Women With HIV Only | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Neonatal death | 1 Participants |
| Women With HIV Only | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Hydrops | 2 Participants |
| Women With HIV Only | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | CNS malformations | 0 Participants |
| Women With HIV Only | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Ocular abnormalities | 18 Participants |
| Women With HIV Only | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Microcephaly | 0 Participants |
| Women Without HIV or ZIKV | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Ocular abnormalities | 5 Participants |
| Women Without HIV or ZIKV | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Microcephaly | 0 Participants |
| Women Without HIV or ZIKV | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Neonatal death | 0 Participants |
| Women Without HIV or ZIKV | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | CNS malformations | 1 Participants |
| Women Without HIV or ZIKV | Incidence of Other Adverse Outcomes Among Offspring of Women Co-infected With HIV and ZIKV, Women Infected With Either HIV or ZIKV Alone. | Hydrops | 0 Participants |
Primary
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.
Time frame: Infant birth to 12 months
Population: Infants enrolled in HIV ZIP who were born to women with HIV or ZIKV infection in pregnancy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Women With HIV Only | 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). | 0 Participants |
Primary
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).
Time frame: Maternal baseline to delivery
Population: Women with HIV and women without HIV enrolled in HIV ZIP during pregnancy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Women With HIV Only | Incidence of ZIKV Infection (Among Pregnant Women With HIV Infection Compared to Those Without HIV Infection). | 0 Participants |
| Women With ZIKV Only | Incidence of ZIKV Infection (Among Pregnant Women With HIV Infection Compared to Those Without HIV Infection). | 0 Participants |
Primary
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.
Time frame: Infant Birth, 3 months, 6 months, 12 months
Population: Infants enrolled in HIV ZIP
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Women With HIV Only | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Length at birth | 48.2 cm |
| Women With HIV Only | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Length at 3 months | 58.5 cm |
| Women With HIV Only | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Length at 6 months | 65.0 cm |
| Women With HIV Only | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Length at 12 months | 75.0 cm |
| Women With HIV Only | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Head circumference at birth | 34.0 cm |
| Women With HIV Only | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Head circumference at 3 months | 40.0 cm |
| Women With HIV Only | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Head circumference at 6 months | 43.0 cm |
| Women With HIV Only | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Head circumference at 12 months | 46.0 cm |
| Women Without HIV or ZIKV | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Head circumference at 12 months | 46.3 cm |
| Women Without HIV or ZIKV | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Length at birth | 48.3 cm |
| Women Without HIV or ZIKV | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Head circumference at birth | 34.0 cm |
| Women Without HIV or ZIKV | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Length at 3 months | 59.5 cm |
| Women Without HIV or ZIKV | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Head circumference at 6 months | 43.8 cm |
| Women Without HIV or ZIKV | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Length at 6 months | 67.0 cm |
| Women Without HIV or ZIKV | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Head circumference at 3 months | 40.3 cm |
| Women Without HIV or ZIKV | Length and Head Circumference Among Children With and Without in Utero Exposure to HIV and/or ZIKV | Length at 12 months | 74.2 cm |
Primary
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.
Time frame: Infant 3 months, 6 months, 12 months
Population: Infants enrolled in HIV ZIP
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 3 months | Yes | 2 Participants |
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 6 months | Missing | 14 Participants |
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 3 months | No | 159 Participants |
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 3 months | Missing | 9 Participants |
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 6 months | Yes | 2 Participants |
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 6 months | No | 154 Participants |
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 12 months | Yes | 3 Participants |
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 12 months | No | 134 Participants |
| Women With HIV Only | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 12 months | Missing | 33 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 12 months | Missing | 9 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 6 months | No | 17 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 3 months | Yes | 2 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 6 months | Missing | 8 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 3 months | No | 20 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 12 months | No | 16 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 3 months | Missing | 3 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 12 months | Yes | 0 Participants |
| Women Without HIV or ZIKV | Neurodevelopment Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Failed screening test at 6 months | Yes | 0 Participants |
Primary
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.
Time frame: Within one month of infant birth, 12 months;
Population: Infants enrolled in HIV ZIP
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Women With HIV Only | Ophthalmologic Structure and Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Ocular abnormalities | 18 Participants |
| Women With HIV Only | Ophthalmologic Structure and Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | No ocular abnormalities | 152 Participants |
| Women Without HIV or ZIKV | Ophthalmologic Structure and Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | No ocular abnormalities | 20 Participants |
| Women Without HIV or ZIKV | Ophthalmologic Structure and Function Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Ocular abnormalities | 5 Participants |
Primary
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).
Time frame: Maternal viral load at delivery
Population: All women with HIV enrolled in HIV ZIP during pregnancy
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <1000 copies/mL | Missing | 51 Participants |
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <40 copies/mL | Yes | 101 Participants |
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <40 copies/mL | No | 22 Participants |
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <40 copies/mL | Missing | 51 Participants |
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <400 copies/mL | Yes | 110 Participants |
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <400 copies/mL | No | 13 Participants |
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <400 copies/mL | Missing | 51 Participants |
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <1000 copies/mL | Yes | 111 Participants |
| Women With HIV Only | Viral Suppression (in HIV-infected Women With ZIKV Co-infection Compared to Those Without ZIKV Co-infection During Pregnancy) at the Time of Delivery. | VL <1000 copies/mL | No | 12 Participants |
Primary
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.
Time frame: Infant Birth, 3 months, 6 months, 12 months
Population: Infants enrolled in HIV ZIP
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Women With HIV Only | Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Weight at birth | 3.2 kg |
| Women With HIV Only | Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Weight at 6 months | 7.7 kg |
| Women With HIV Only | Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Weight at 3 months | 5.9 kg |
| Women With HIV Only | Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Weight at 12 months | 10.0 kg |
| Women Without HIV or ZIKV | Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Weight at 3 months | 5.7 kg |
| Women Without HIV or ZIKV | Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Weight at birth | 3.2 kg |
| Women Without HIV or ZIKV | Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Weight at 12 months | 9.8 kg |
| Women Without HIV or ZIKV | Weight Among Children With or Without in Utero Exposure to HIV and/or ZIKV | Weight at 6 months | 8.2 kg |