Prospective Cohort Study of HIV and Zika in Infants and Pregnancy

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.

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.