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

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT02778204
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), ViiV Healthcare (Industry), GlaxoSmithKline (Industry)
47
9
4
29.5
5.2
0.2

Study Details

Study Description

Brief Summary

This study aimed to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in infants at risk for mother-to-child HIV transmission, and to determine an appropriate dose of maraviroc during the first six weeks of life.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

Maraviroc is a C-C Chemokine Receptor 5 (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 was to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in HIV-1-exposed infants at risk for mother-to-child HIV transmission. This study also aimed to determine an appropriate dose of maraviroc during the first six weeks of life.

The study allowed up to 72 mother-infant pairs in two cohorts to achieve a target of 36 evaluable infants receiving the final recommended dose of maraviroc. Because maraviroc interacts with the antiretroviral drug efavirenz (EFV) in adults, infants in this study were stratified within the cohorts based on their exposure to maternal EFV. Cohort 1 was stratified by in utero exposure to maternal EFV, with infants in both strata receiving a single dose of maraviroc solution within three days of birth and another single dose at Week 1 of life. Stratum 1A included infants without in utero exposure to maternal EFV during the eight weeks immediately before delivery. Stratum 1B included infants with in utero exposure to maternal EFV for a minimum of two weeks immediately before delivery.

Cohort 2 was stratified by exposure to maternal EFV after birth, with infants in both strata receiving maraviroc oral solution twice daily starting within three 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 was 8 mg/kg dose given twice daily. Stratum 2A included infants without any exposure to maternal EFV either in utero during the eight weeks immediately before delivery or while breastfeeding. Stratum 2B included 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 attended an entry visit within three days after the infant's birth. Participants attended five to six study visits through Week 16. Visits included medical history reviews, physical examinations, blood collection from the mother and/or infant, HIV testing, and adherence counseling.

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection
Actual Study Start Date :
Jun 5, 2017
Actual Primary Completion Date :
Sep 6, 2019
Actual Study Completion Date :
Nov 20, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1 Stratum 1A

Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.

Drug: Maraviroc
8 mg/kg oral solution as a single dose.

Experimental: Cohort 1 Stratum 1B

Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.

Drug: Maraviroc
8 mg/kg oral solution as a single dose.

Experimental: Cohort 2 Stratum 2A

Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.

Drug: Maraviroc
8 mg/kg oral solution given twice daily.

Experimental: Cohort 2 Stratum 2B

Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz

Drug: Maraviroc
8 mg/kg oral solution given twice daily.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding [Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).]

    Percentage (%) of failure and Clopper-Pearson 95% Confidence Interval (CI). Failure is defined as having: Any life threatening adverse event (AE), including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug

  2. Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis [Measured from first dose of maraviroc to Week 6 Visit (up to 42 days)]

    Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug

  3. Number of Participants Failing to Meet PK Target [Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).]

    Number of failures. The pharmacokinetic (PK) target is Average Concentration (Cavg) greater than or equal to 75 ng/mL (based on a dose interval of every 12 hours). Failure is defined as Cavg <75 ng/mL at each intensive PK visit. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

  4. Pharmacokinetic (PK) Parameter: Average Concentration (Cavg) [Cohort 1: Measured at Entry and Week 1 Visit. Cohort 2: Measured at Week 1 and Week 4 Visit]

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). Cavg was determined as the area-under-the-curve (AUC) divided by the dose interval, tau (τ) of every 12 hours. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

  5. Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC) [Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).]

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). For Cohort 1 (single doses), area-under-the-curve (AUC) was determined from time zero to infinity. For Cohort 2 (at steady-state), area-under-the-curve (AUC) was determined from time pre-dose to tau (12 hours). For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

  6. Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax) [Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).]

    Pharmacokinetic parameters were determined from plasma concentration-time profiles. Cmax was the observed highest concentration. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

  7. Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax) [Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).]

    Pharmacokinetic parameters were determined from plasma concentration-time profiles. Tmax was the time at which Cmax, the observed highest concentration, occurred. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

  8. Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau) [Measured at Week 1 and Week 4 Visit]

    Pharmacokinetic parameters were determined from plasma concentration-time profiles. Ctau was the observed concentration at the trough time of 12 hours post-dose with steady-state dosing. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Secondary Outcome Measures

  1. Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding [Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)]

    Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug

  2. Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis [Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)]

    Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 3 Days
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Mother was of legal age to provide independent informed consent for research participation and was willing and able to provide written informed consent for her and her infant's participation in this study.

  • Mother had 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 met 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 were 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 were 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 was not receiving maternal EFV. Note: Breastfeeding and formula feeding infants were 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, intended to breastfeed for a minimum of six weeks and continued to receive maternal EFV while breastfeeding. Note: Only breastfeeding infants were 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 was less than or equal to 3 days old.

  • At entry, infant had 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 had initiated antiretroviral prophylaxis that did not include a potent CYP3A4 inhibitor or inducer. See the protocol for more information.

  • At entry, infant was 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 had 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 was receiving any disallowed medication listed in the protocol.

  • Mother received maraviroc during pregnancy.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Usc La Nichd Crs Los Angeles California United States 90089
2 Univ. of Colorado Denver NICHD CRS Aurora Colorado United States 80045
3 Rush Univ. Cook County Hosp. Chicago NICHD CRS Chicago Illinois United States 60612
4 Lurie Children's Hospital of Chicago (LCH) CRS Chicago Illinois United States 60614-3393
5 St. Jude Children's Research Hospital CRS Memphis Tennessee United States 38105-3678
6 Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS Kericho Kenya 20200
7 Soweto IMPAACT CRS Johannesburg Gauteng South Africa 1862
8 Umlazi CRS Durban Kwa Zulu Natal South Africa 4001
9 Siriraj Hospital ,Mahidol University NICHD CRS Bangkok Bangkoknoi Thailand 10700

Sponsors and Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • ViiV Healthcare
  • GlaxoSmithKline

Investigators

  • Study Chair: Mark Mirochnick, MD, Boston University School of Medicine/Boston Medical Center

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02778204
Other Study ID Numbers:
  • IMPAACT 2007
  • 20734
First Posted:
May 19, 2016
Last Update Posted:
Jan 4, 2022
Last Verified:
Dec 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details Accrual occurred between June 2017 and July 2019 in Kenya, Thailand, South Africa, and the United States at 9 different medical clinic sites. Pregnant mothers were screened and subsequently enrolled for 1 day at the same day their newborn infants were enrolled (within 3 days of life).
Pre-assignment Detail The sample size of the study (47) represents the infants enrolled. As multiple births are disallowed in the study, this also represents the total mother-infant pairs.
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Period Title: Overall Study
STARTED 8 7 16 16
COMPLETED 6 7 12 12
NOT COMPLETED 2 0 4 4

Baseline Characteristics

Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B Total
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz Total of all reporting groups
Overall Participants 8 7 16 16 47
Age (days) [Median (Inter-Quartile Range) ]
Mean (Standard Deviation)
1.5
0
1
2
2
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]
29.5
26
32
32
31
Sex: Female, Male (Count of Participants)
Female
5
62.5%
4
57.1%
7
43.8%
7
43.8%
23
48.9%
Male
3
37.5%
3
42.9%
9
56.3%
9
56.3%
24
51.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
3
37.5%
0
0%
2
12.5%
0
0%
5
10.6%
Not Hispanic or Latino
5
62.5%
7
100%
14
87.5%
16
100%
42
89.4%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
3
18.8%
0
0%
3
6.4%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
Black or African American
5
62.5%
7
100%
10
62.5%
16
100%
38
80.9%
White
3
37.5%
0
0%
3
18.8%
0
0%
6
12.8%
More than one race
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (participants) [Number]
United States
7
87.5%
0
0%
13
81.3%
0
0%
20
42.6%
South Africa
1
12.5%
7
100%
0
0%
14
87.5%
22
46.8%
Thailand
0
0%
0
0%
3
18.8%
0
0%
3
6.4%
Kenya
0
0%
0
0%
0
0%
2
12.5%
2
4.3%
Birth Weight (kilograms) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kilograms]
3.2
3.4
3.0
3.0
3.05
Birth Length (centimeters) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [centimeters]
50.0
50.0
49.0
48.5
49.0
Gestational Age (weeks) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [weeks]
38.5
39.0
39.0
40.0
39.0
APGAR at 1 minute (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]
9.0
8.0
8.5
9.0
9.0
Alanine Aminotransferase (ALT) (ukat/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ukat/L]
0.2
0.2
0.2
0.2
0.2
Aspartate Aminotransferase (AST) (ukat/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ukat/L]
0.7
1.1
0.9
1.0
0.9
Total Bilirubin (umol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [umol/L]
39.3
44.0
76.1
75.3
50.7
Creatinine (umol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [umol/L]
70.7
62.0
61.9
69.0
66
Platelets (10^9 platelets/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [10^9 platelets/L]
274.0
297.0
252.5
311.0
289.0
Hemoglobin (g/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [g/L]
163.0
178.0
166.5
179.0
170.0
White Blood Cell Count (WBC) (10^9 cells/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [10^9 cells/L]
14.6
17.3
15.5
12.6
14.6

Outcome Measures

1. Primary Outcome
Title Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding
Description Percentage (%) of failure and Clopper-Pearson 95% Confidence Interval (CI). Failure is defined as having: Any life threatening adverse event (AE), including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Time Frame Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).

Outcome Measure Data

Analysis Population Description
Safety-evaluable population are those who were taking maraviroc for the expected time-frame (Cohort 1: through 7 day post-dose visit, Cohort 2: Through week 6)
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 6 7 12 12
Number (95% Confidence Interval) [percentage of participants]
0
0%
0
0%
0
0%
0
0%
2. Primary Outcome
Title Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis
Description Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Time Frame Measured from first dose of maraviroc to Week 6 Visit (up to 42 days)

Outcome Measure Data

Analysis Population Description
Analysis Endpoint includes all treated participants
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 8 7 16 16
Number (95% Confidence Interval) [percentage of participants]
0
0%
0
0%
0
0%
0
0%
3. Primary Outcome
Title Number of Participants Failing to Meet PK Target
Description Number of failures. The pharmacokinetic (PK) target is Average Concentration (Cavg) greater than or equal to 75 ng/mL (based on a dose interval of every 12 hours). Failure is defined as Cavg <75 ng/mL at each intensive PK visit. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Time Frame Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

Outcome Measure Data

Analysis Population Description
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. In Cohort 1 Stratum 1A and 1B at the week 1 visit (Second Visit), only 3 PK sample were drawn (pre-dose, 1-2 hours post-dose, and 22-26 hours post-dose). Maraviroc was only measurable (above assay limit) at 1 time point (1-2 hours post-dose). Therefore, AUC (hence Cavg) could not be estimated with non-compartmental methods from only 1 concentration and thus the number analyzed was 0.
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 6 7 13 12
First Visit
0
0%
0
0%
3
18.8%
4
25%
Second Visit
4
50%
5
71.4%
4. Primary Outcome
Title Pharmacokinetic (PK) Parameter: Average Concentration (Cavg)
Description Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). Cavg was determined as the area-under-the-curve (AUC) divided by the dose interval, tau (τ) of every 12 hours. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Time Frame Cohort 1: Measured at Entry and Week 1 Visit. Cohort 2: Measured at Week 1 and Week 4 Visit

Outcome Measure Data

Analysis Population Description
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. In Cohort 1 Stratum 1A and 1B at the week 1 visit (Second Visit), only 3 PK sample were drawn (pre-dose, 1-2 hours post-dose, and 22-26 hours post-dose). Maraviroc was only measurable (above assay limit) at 1 time point (1-2 hours post-dose). Therefore, AUC (hence Cavg) could not be estimated with non-compartmental methods from only 1 concentration and thus the number analyzed was 0.
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 6 7 13 12
First Visit
190.47
375.47
152.24
124.67
Second Visit
93.58
101.39
5. Primary Outcome
Title Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC)
Description Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). For Cohort 1 (single doses), area-under-the-curve (AUC) was determined from time zero to infinity. For Cohort 2 (at steady-state), area-under-the-curve (AUC) was determined from time pre-dose to tau (12 hours). For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Time Frame Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

Outcome Measure Data

Analysis Population Description
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. In Cohort 1 Stratum 1A and 1B at the week 1 visit (Second Visit), only 3 PK sample were drawn (pre-dose, 1-2 hours post-dose, and 22-26 hours post-dose). Maraviroc was only measurable (above assay limit) at 1 time point (1-2 hours post-dose). Therefore, AUC (hence Cavg) could not be estimated with non-compartmental methods from only 1 concentration and thus the number analyzed was 0.
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 6 7 13 12
First Visit
2285.68
4506.17
1826.87
1496.05
Second Visit
1122.99
1216.62
6. Primary Outcome
Title Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax)
Description Pharmacokinetic parameters were determined from plasma concentration-time profiles. Cmax was the observed highest concentration. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Time Frame Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

Outcome Measure Data

Analysis Population Description
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results.
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 6 7 13 12
First Visit
227.3
550.5
256.9
308.8
Second Visit
128.9
163.4
416.5
221.8
7. Primary Outcome
Title Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax)
Description Pharmacokinetic parameters were determined from plasma concentration-time profiles. Tmax was the time at which Cmax, the observed highest concentration, occurred. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Time Frame Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

Outcome Measure Data

Analysis Population Description
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results.
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 6 7 13 12
First Visit
4.68
1.52
1.50
3.00
Second Visit
1.18
1.08
1.50
2.19
8. Primary Outcome
Title Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau)
Description Pharmacokinetic parameters were determined from plasma concentration-time profiles. Ctau was the observed concentration at the trough time of 12 hours post-dose with steady-state dosing. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Time Frame Measured at Week 1 and Week 4 Visit

Outcome Measure Data

Analysis Population Description
Analysis population included Cohort 2 dose-finding evaluable participants with intensive pharmacokinetic (PK) results.
Arm/Group Title Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 13 12
Week 1 Visit
27.9
23.4
Week 4 Visit
34.4
54.9
9. Secondary Outcome
Title Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding
Description Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Time Frame Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)

Outcome Measure Data

Analysis Population Description
Safety-evaluable population are those who were taking maraviroc for the expected time-frame (Cohort 1: through 7 day post-dose visit, Cohort 2: Through week 6)
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 6 7 12 12
Number (95% Confidence Interval) [percentage of participants]
0
0%
0
0%
0
0%
0
0%
10. Secondary Outcome
Title Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis
Description Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Time Frame Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)

Outcome Measure Data

Analysis Population Description
All treated participants
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Measure Participants 8 7 16 16
Number (95% Confidence Interval) [percentage of participants]
0
0%
0
0%
0
0%
0
0%

Adverse Events

Time Frame From study entry to study completion at Week 16 or premature study discontinuation
Adverse Event Reporting Description All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Arm/Group Title Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Arm/Group Description Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
All Cause Mortality
Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/8 (0%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Serious Adverse Events
Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/8 (25%) 1/7 (14.3%) 4/16 (25%) 2/16 (12.5%)
Blood and lymphatic system disorders
Haemolytic anaemia 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Cardiac disorders
Cyanosis 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Congenital, familial and genetic disorders
Hypospadias 0/8 (0%) 1/7 (14.3%) 0/16 (0%) 0/16 (0%)
Hepatobiliary disorders
Jaundice 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Infections and infestations
Escherichia urinary tract infection 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Pneumonia bacterial 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Sepsis neonatal 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Staphylococcal sepsis 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Investigations
Haemoglobin decreased 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Neutrophil count decreased 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Weight decreased 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Metabolism and nutrition disorders
Failure to thrive 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 1/16 (6.3%)
Nervous system disorders
Slow response to stimuli 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Tremor 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Other (Not Including Serious) Adverse Events
Cohort 1 Stratum 1A Cohort 1 Stratum 1B Cohort 2 Stratum 2A Cohort 2 Stratum 2B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 7/8 (87.5%) 7/7 (100%) 15/16 (93.8%) 14/16 (87.5%)
Blood and lymphatic system disorders
Haemolytic anaemia 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Cardiac disorders
Tachycardia 0/8 (0%) 0/7 (0%) 2/16 (12.5%) 0/16 (0%)
Congenital, familial and genetic disorders
Congenital melanocytic naevus 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Congenital syphilis 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Hypospadias 0/8 (0%) 1/7 (14.3%) 0/16 (0%) 0/16 (0%)
Eye disorders
Conjunctival pallor 0/8 (0%) 1/7 (14.3%) 0/16 (0%) 1/16 (6.3%)
Eye discharge 1/8 (12.5%) 1/7 (14.3%) 0/16 (0%) 3/16 (18.8%)
Ocular hyperaemia 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Orbital oedema 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Gastrointestinal disorders
Abdominal distension 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Abdominal pain 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Diarrhoea 0/8 (0%) 1/7 (14.3%) 3/16 (18.8%) 0/16 (0%)
Infantile colic 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Infantile vomiting 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Mouth ulceration 0/8 (0%) 1/7 (14.3%) 0/16 (0%) 0/16 (0%)
Teething 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
General disorders
Face oedema 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Feeling hot 0/8 (0%) 0/7 (0%) 0/16 (0%) 2/16 (12.5%)
Pyrexia 0/8 (0%) 1/7 (14.3%) 2/16 (12.5%) 1/16 (6.3%)
Hepatobiliary disorders
Hyperbilirubinaemia 0/8 (0%) 0/7 (0%) 2/16 (12.5%) 0/16 (0%)
Hyperbilirubinaemia neonatal 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Jaundice 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Infections and infestations
Acarodermatitis 0/8 (0%) 1/7 (14.3%) 0/16 (0%) 0/16 (0%)
Conjunctivitis bacterial 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Escherichia urinary tract infection 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Genital candidiasis 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Impetigo 0/8 (0%) 2/7 (28.6%) 0/16 (0%) 0/16 (0%)
Nasopharyngitis 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Ophthalmia neonatorum 1/8 (12.5%) 0/7 (0%) 1/16 (6.3%) 2/16 (12.5%)
Oral candidiasis 1/8 (12.5%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Pneumonia bacterial 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 1/16 (6.3%)
Sepsis neonatal 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Staphylococcal sepsis 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Tinea versicolour 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Injury, poisoning and procedural complications
Contusion 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Eyelid injury 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Investigations
Alanine aminotransferase increased 0/8 (0%) 1/7 (14.3%) 0/16 (0%) 1/16 (6.3%)
Aspartate aminotransferase increased 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 3/16 (18.8%)
Bilirubin conjugated increased 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Blood bilirubin increased 2/8 (25%) 0/7 (0%) 9/16 (56.3%) 4/16 (25%)
Blood potassium increased 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Cardiac murmur 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Haemoglobin decreased 4/8 (50%) 4/7 (57.1%) 11/16 (68.8%) 5/16 (31.3%)
Neutrophil count decreased 0/8 (0%) 2/7 (28.6%) 5/16 (31.3%) 7/16 (43.8%)
Weight decreased 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
White blood cell count decreased 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Metabolism and nutrition disorders
Failure to thrive 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 1/16 (6.3%)
Hyperkalaemia 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Malnutrition 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Poor feeding infant 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Underweight 3/8 (37.5%) 1/7 (14.3%) 4/16 (25%) 0/16 (0%)
Musculoskeletal and connective tissue disorders
Acquired macrocephaly 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Nervous system disorders
Hypertonia 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Hypotonia 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Pregnancy, puerperium and perinatal conditions
Jaundice neonatal 1/8 (12.5%) 0/7 (0%) 3/16 (18.8%) 2/16 (12.5%)
Small for dates baby 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Psychiatric disorders
Irritability 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 0/8 (0%) 1/7 (14.3%) 2/16 (12.5%) 4/16 (25%)
Hypoxia 0/8 (0%) 0/7 (0%) 2/16 (12.5%) 0/16 (0%)
Nasal congestion 0/8 (0%) 3/7 (42.9%) 2/16 (12.5%) 3/16 (18.8%)
Neonatal hypoxia 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Rhinorrhoea 0/8 (0%) 0/7 (0%) 2/16 (12.5%) 2/16 (12.5%)
Sneezing 0/8 (0%) 0/7 (0%) 2/16 (12.5%) 0/16 (0%)
Tachypnoea 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Use of accessory respiratory muscles 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Skin and subcutaneous tissue disorders
Dermatitis diaper 1/8 (12.5%) 2/7 (28.6%) 0/16 (0%) 2/16 (12.5%)
Erythema toxicum neonatorum 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Intertrigo 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Miliaria 0/8 (0%) 0/7 (0%) 0/16 (0%) 2/16 (12.5%)
Papule 0/8 (0%) 2/7 (28.6%) 0/16 (0%) 1/16 (6.3%)
Petechiae 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Pruritus 0/8 (0%) 0/7 (0%) 0/16 (0%) 1/16 (6.3%)
Rash 1/8 (12.5%) 5/7 (71.4%) 1/16 (6.3%) 3/16 (18.8%)
Rash neonatal 0/8 (0%) 2/7 (28.6%) 1/16 (6.3%) 3/16 (18.8%)
Rash papular 1/8 (12.5%) 0/7 (0%) 0/16 (0%) 0/16 (0%)
Seborrhoeic dermatitis 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)
Vascular disorders
Haematoma 0/8 (0%) 0/7 (0%) 1/16 (6.3%) 0/16 (0%)

Limitations/Caveats

As with other Antiretrovirals (ARVs) in young infants, maraviroc PK parameters showed high intra- and inter-participant variability.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights

Results Point of Contact

Name/Title Melissa Allen, Director, IMPAACT Operations Center
Organization Family Health International (FHI 360)
Phone (919) 405-1429
Email mallen@fhi360.org
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02778204
Other Study ID Numbers:
  • IMPAACT 2007
  • 20734
First Posted:
May 19, 2016
Last Update Posted:
Jan 4, 2022
Last Verified:
Dec 1, 2021