IMPAACT P1106: Pharmacokinetic Characteristics of Antiretrovirals and Tuberculosis Medicines in Low Birth Weight Infants

P1106 is Phase IV prospective pharmacokinetic (PK) study of low birth weight infants who are receiving or will be receiving as part of clinical care nevirapine (NVP) prophylaxis, tuberculosis (TB) prophylaxis or treatment and/or combination antiretroviral (ARV) treatment containing lopinavir/ritonavir (LPV/r). The study is designed to describe the pharmacokinetics and safety of NVP, INH, RIF, and LPV/r in these infants receiving the drug(s) as part of clinical care.

Study Overview

• Status: Completed
• Conditions: HIV; Tuberculosis; Low-Birth-Weight Infant

• Study Type: Observational
• Enrollment (Actual): 124

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • Soweto IMPAACT CRS (8052)
  • Western Cape Province
    • Cape Town, Western Cape Province, South Africa, 7505
      • Family Clinical Research Unit (FAM-CRU) CRS (8950)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Low birth weight (LBW) infants less than or equal to 2500 grams at birth who are receiving or will be receiving as part of clinical care nevirapine (NVP) prophylaxis, tuberculosis (TB) prophylaxis or treatment and/or combination antiretroviral (ARV) treatment containing lopinavir/ritonavir (LPV/r)

Description

Inclusion Criteria:

Inclusion Criteria for Arms 1 and 3 (HIV-exposed infants):

• Breastfeeding infants born to HIV-infected mothers who are receiving either no ARV therapy or ARV therapy that does not include NVP
• Age 7 to 14 days
• Birth weight less than 2500 grams
• Receiving or will be receiving prophylaxis as prescribed by clinical care provider as follows: NVP (Arm 1), NVP plus INH (Arm 2), NVP plus INH plus RIF (Arm 3)
• Parent or legal guardian able and willing to provide written informed consent. [Note to sites: modify per locally relevant language].

Inclusion Criteria for Arm 2 (HIV-exposed infants):

• Breastfeeding infants born to HIV-infected mothers who are receiving either no ARV therapy or ARV therapy that does not include NVP
• Age 7 to 84 days
• Birth weight less than or equal to 4000 grams
• Receiving or will be receiving prophylaxis as prescribed by clinical care provider as follows: NVP (Arm 1), NVP plus INH (Arm 2), NVP plus INH plus RIF (Arm 3)
• Parent or legal guardian able and willing to provide written informed consent. [Note to sites: modify per locally relevant language].

Inclusion Criteria for Arm 4 (HIV-unexposed but TB exposed infants):

• Age 7 to 84 days
• Birth weight less than or equal to 4000 grams
• Receiving prophylaxis with INH alone or INH plus RIF as prescribed by clinical care provider
• Not receiving any therapy for HIV prophylaxis or treatment
• Parent or legal guardian able and willing to provide written informed consent. [Note to sites: modify per locally relevant language].

Inclusion Criteria for Arms 5 and 6 (HIV-infected infants):

• Documentation of HIV-1 infection defined as positive HIV DNA PCR done as part of clinical care. An HIV RNA confirmatory test must be done at study entry but results may be pending at time of enrollment.
• Birth weight less than or equal to 4000 grams
• Age less than or equal to 12 weeks (defined as 84 days)
• Intention by clinical care provider to prescribe LPV/r plus 2 NRTIs and no RIF (Arm 5) or LPV/r plus 2 NRTIs plus RIF (Arm 6)
• Parent or legally acceptable representative able and willing to provide written informed consent. [Note to sites: modify per locally relevant language].

Exclusion Criteria:

Any severe congenital malformation or other medical condition incompatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort
Arm 1; Breastfeeding infants 7 to 14 days of age with birth weight less than 2500 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected and TB negative; infant receiving NVP prophylaxis but not TB prophylaxis or treatment
Arm 2; Breastfeeding infants 7 to 84 days of age with birth weight less than or equal to 4000 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected with active TB disease; infant receiving NVP prophylaxis plus isoniazid (INH) but not rifampicin (RIF) for TB prophylaxis
Arm 3; Breastfeeding infants 7 to 14 days of age with birth weight less than 2500 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected with active TB disease; infant receiving NVP prophylaxis plus INH plus RIF for TB prophylaxis or treatment
Arm 4; Breast or formula feeding infants 7 to 84 days of age with birth weight less than or equal to 4000 grams born to HIV-uninfected mothers with active TB disease; infant receiving INH alone or INH plus RIF for TB prophylaxis
Arm 5; Breast or formula feeding infants newly diagnosed with HIV infection weighing less than or equal to 4000 grams at birth and are less than or equal to 12 weeks of age. Infants who were enrolled in Arms 1, 2 or 3 and later determined to be HIV infected are then are eligible to enroll in Arm 5 if started on an LPV/r regimen. Infants initiating treatment with LPV/r plus 2 NRTIs, and not receiving RIF (but may be receiving INH)
Arm 6; Breast or formula feeding infants newly diagnosed with HIV infection weighing less than 2500 grams at birth and are less than or equal to 12 weeks of age. Infants who were enrolled in Arms 1, 2 or 3 and later determined to be HIV infected are then are eligible to enroll in Arm 6 if started on an LPV/r regimen. Infants initiating treatment with LPV/r plus 2 NRTIs, and receiving RIF (and may be receiving INH)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance of NVP, INH, RIF, and LPV/r after oral dose	Apparent clearance (CL/F) of NVP, INH, RIF, and LPV/r	Week 24 of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary safety endpoints	Number of participants with adverse events of grade 3 or 4 severity, death, or serious adverse clinical events	Study duration

Collaborators and Investigators

• Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Chair: Mark Cotton, MD, MBChB, FCPaed, MMED, University of Stellenbosch; Study Chair: Mark H Mirochnick, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2015
• Primary Completion (Actual): February 14, 2020
• Study Completion (Actual): February 14, 2020

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: March 3, 2015
• First Posted (Estimate): March 9, 2015

Study Record Updates

• Last Update Posted (Actual): August 6, 2021
• Last Update Submitted That Met QC Criteria: July 31, 2021
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Body Weight; Birth Weight
• Other Study ID Numbers: IMPAACT P1106; 11882 (Other Identifier: DAIDS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• IPD Sharing Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.; For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network.; By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)