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

NCT ID: NCT02383849

Last Updated: 2021-08-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 124 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-08-04
• Study Completion Date: 2020-02-14

Brief Summary

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.

Conditions

Low-Birth-Weight Infant; Tuberculosis; HIV

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

No interventions assigned to this group

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

No interventions assigned to this group

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

No interventions assigned to this group

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

No interventions assigned to this group

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)

No interventions assigned to this group

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)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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].

• 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].

• 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].

• 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.

• Minimum Eligible Age: 7 Days
• Maximum Eligible Age: 84 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Cotton, MD, MBChB, FCPaed, MMED

Role: STUDY_CHAIR

University of Stellenbosch

Mark H Mirochnick, MD

Role: STUDY_CHAIR

Boston Medical Center

Locations

Soweto IMPAACT CRS (8052)

Johannesburg, Gauteng, South Africa

Family Clinical Research Unit (FAM-CRU) CRS (8950)

Cape Town, Western Cape, South Africa

Countries

South Africa

References

Bekker A, Yang J, Wang J, Cotton MF, Cababasay M, Wiesner L, Moye J, Browning R, Nakwa FL, Rabie H, Violari A, Mirochnick M, Cressey TR, Capparelli EV. Safety and Pharmacokinetics of Lopinavir/Ritonavir Oral Solution in Preterm and Term Infants Starting Before 3 Months of Age. Pediatr Infect Dis J. 2024 Apr 1;43(4):355-360. doi: 10.1097/INF.0000000000004243. Epub 2024 Jan 4.

Reference Type: DERIVED

PMID: 38190642 (View on PubMed)

Other Identifiers

11882

Identifier Type: OTHER

Identifier Source: secondary_id

IMPAACT P1106

Identifier Type: -

Identifier Source: org_study_id