Evaluating the Safety and Pharmacokinetics of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection

Maraviroc is a CCR5 receptor antagonist used to treat HIV infection in adults. Adding
maraviroc to a standard of care prophylaxis regimen may also reduce the risk of perinatal
transmission of HIV. The purpose of this study is to evaluate the safety, tolerability, and
pharmacokinetics of maraviroc in HIV-1-exposed infants at risk for mother-to-child HIV
transmission. This study will also determine an appropriate dose of maraviroc during the
first 6 weeks of life.

The study will enroll up to 72 mother-infant pairs in two cohorts. Because maraviroc
interacts with the antiretroviral drug efavirenz (EFV) in adults, infants in this study will
be stratified within the cohorts based on their exposure to maternal EFV. Cohort 1 will be
stratified by in utero exposure to maternal EFV, with infants in both strata receiving a
single dose of maraviroc solution within 3 days of birth and another single dose at Week 1 of
life. Stratum 1A includes infants without in utero exposure to maternal EFV during the 8
weeks immediately before delivery. Stratum 1B includes infants with in utero exposure to
maternal EFV for a minimum of 2 weeks immediately before delivery.

Cohort 2 will be stratified by exposure to maternal EFV after birth, with infants in both
strata receiving maraviroc oral solution twice daily starting within 3 days of birth and
continuing for up to 42 days. Based on evaluation of the Cohort 1 data, the initial daily
dose of maraviroc oral solution to be administered in Cohort 2 will be 8 mg/kg dose given
twice daily. Stratum 2A includes infants without any exposure to maternal EFV either in utero
during the 8 weeks immediately before delivery or while breastfeeding. Stratum 2B includes
breastfeeding infants with exposure to maternal EFV both in utero and after birth while
breastfeeding, for a minimum of 2 weeks immediately before delivery and while breastfeeding.

Participants will attend an entry visit within 3 days after the infant's birth. Participants
will attend 5 to 6 study visits through Month 4. Visits may include medical history reviews,
physical examinations, blood collection from the mother and/or infant, HIV testing, and
adherence counseling.

Inclusion Criteria:

- Mother is of legal age to provide independent informed consent for research
participation and is willing and able to provide written informed consent for her and
her infant's participation in this study.

- Mother has confirmed HIV-1 infection based on testing of two samples collected at
different time points. More information on this criterion can be found in the
protocol.

- At entry, infant meets EFV exposure requirements, based on mother's report and
confirmed by medical records if available, as follows:

- For Cohort 1, Stratum 1A: Infant born to a mother who did not receive EFV during
the eight weeks immediately prior to delivery. Note: Breastfeeding and formula
feeding infants are eligible for this stratum.

- For Cohort 1, Stratum 1B: Infant born to a mother who received EFV for a minimum
of two weeks immediately prior to delivery. Note: Breastfeeding and formula
feeding infants are eligible for this stratum.

- For Cohort 2, Stratum 2A: Infants born to a mother who did not receive EFV during
the eight weeks immediately prior to delivery and if breastfeeding, mother is not
receiving maternal EFV. Note: Breastfeeding and formula feeding infants are
eligible for this stratum.

- For Cohort 2, Stratum 2B: Breastfeeding infants born to a mother who received EFV
for a minimum of two weeks immediately prior to delivery, intends to breastfeed
for a minimum of six weeks and will continue to receive maternal EFV while
breastfeeding. Note: Only breastfeeding infants are eligible for this stratum.

- At birth, infant's estimated gestational age was at least 37 weeks. Note: If
gestational age at birth is not documented in the infant's available birth records,
study staff may assess gestational age at the earliest possible opportunity during the
screening period and use this assessment for purposes of eligibility determination.

- At birth, infant's weight was at least 2 kg. Note: If weight at birth is not
documented in the infant's available birth records, study staff may assess infant
weight at the earliest possible opportunity during the screening period and use this
assessment for purposes of eligibility determination.

- At entry, infant is less than or equal to 3 days old.

- At entry, infant has the following lab values:

- Grade 0 alanine transaminase (ALT) (normal)

- Less than or equal to Grade 1 aspartate aminotransferase (AST) and total
bilirubin

- Less than or equal to Grade 2 hemoglobin, white blood cell counts, platelet
counts

- At entry, infant has initiated antiretroviral prophylaxis that does not include a
potent CYP3A4 inhibitor or inducer. See the protocol for more information.

- At entry, infant is assessed by the site investigator or designee as generally healthy
based on review of available medical records, other available medical history
information, and physical examination findings.

- Born after singleton delivery (not after multiple birth).

Exclusion Criteria:

- Infant has any other condition that, in the opinion of the site investigator or
designee, would make participation in the study unsafe, complicate interpretation of
study outcome data, or otherwise interfere with achieving the study objectives; for
example, severe congenital malformation, other medical condition, or clinically
significant finding from physical examination.

- At entry, any positive infant HIV nucleic acid test result (results are not required
to be available prior to entry but any positive results obtained prior to entry are
exclusionary).

- At entry, infant or breastfeeding mother is receiving any disallowed medication listed
in the protocol.

- Mother received maraviroc during pregnancy.