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

Study Overview
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Brief Summary
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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.

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

Conditions
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HIV, Low-Birth-Weight Infant, Tuberculosis

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 7 Days
Maximum Age: 84 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1<br>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<br>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<br>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<br>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<br>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<br>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?
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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 |