HIV/AIDS Tuberculosis
Conditions
Interventions
Pharmacokinetics of medications under study
Sponsors
National Institute of Allergy and Infectious Diseases
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Mother is of legal age or otherwise able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures, and is willing and able to provide written informed consent for her own and her infant’s participation in this study. Prior to study entry, HIV status confirmed as HIV infected At study entry, pregnant and in one of the following two enrollment windows, based on best available obstetrical estimate of gestational age: • Second trimester: gestational age of 20 0/7 to 26 6/7 weeks • Third trimester: gestational age of 30 0/7 to 37 6/7 weeks At study entry, receiving at least two of the following first-line TB treatment drugs under study AND at least one of the following ARV drugs or drug combinations under study, based on maternal report and available medical records: First-line TB treatment drugs: • Isoniazid (INH) 4-6 mg/kg (max 300 mg) q.d. • Rifampin (RIF) 8-12 mg/kg (max 600 mg) q.d. • Rifabutin (RFB) 150-300 mg q.d. • Ethambutol (EMB) 15-20 mg/kg q.d. • Pyrazinamide (PZA) 20-30 mg/kg q.d. • Moxifloxacin (MFX) 400 mg or 800mg q.d. ARVs: Arm 3.1 Dolutegravir (DTG) 50 mg b.i.d. when combined with RIF or 50 mg q.d. if RIF is not part of the TB regimen Arm 3.2 Atazanavir/ritonavir (ATV/r) =300/100 mg q.d. or Darunavir/ritonavir (DRV/r) = 600/100 mg b.i.d. Arm 3.3 Lopinavir/ritonavir (LPV/r) 800/200 mg b.i.d. At study entry, has been receiving the drug combination under study at the required dose for at least two weeks based on maternal report and available medical records. At study entry, assessed by study staff as having no identified barriers to completing initial PK sampling within 20 0/7 – 26 6/7 weeks gestation (second trimester) or 30 0/7 to 37 6/7 weeks gestation (third trimester) and within 14 days of enrollment. At study entry, if receiving a generic ARV or TB formulation of the drug or drug combination under study, approval of the formulation.
Exclusion criteria
Exclusion criteria: At study entry, mother has received within the past 14 days medicines known to interfere with absorption, metabolism, or clearance of the drug or drug combination under study based on maternal report and available medical records. At study entry, has a clinical or laboratory finding or condition that, in the opinion of the site investigator, is likely to require a change of the ARV or TB drug under study during the period of study follow-up. 4.2.3 Arms 1.3, 1.4 and 1.5 only: At study entry, mother has received TDF-based therapy within the past 6 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maternal breast milk/maternal plasma concentration ratio Infant plasma concentration Arms 3.1, 3.2 and 3.3: DTG, ATV, DRV, LPV, INH, RIF, RFB, EMB, PZA, MFX: AUC at 2T, 3T and PP | — |
Secondary
| Measure | Time frame |
|---|---|
| Grade 3 or higher maternal adverse events | — |
Countries
Kenya
Contacts
Public ContactCHARLES KILEL
Kenya Medical Research Institute Walter Reed Project Clinical Research Center
Outcome results
None listed