Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy

• Status: Completed
• Trial end date: 2020-09-30
• Target enrollment: 0
• Participant gender: Female

Summary

The purpose of this study is to evaluate the pharmacokinetics (PKs) of antiretroviral (ARV) and tuberculosis (TB) medications in pregnant women and their infants. (Pharmacokinetics are the various interactions between a drug and the body.) This study will also evaluate the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives. The PKs of these drugs will be evaluated by measuring the amount of medicine present in blood and/or vaginal secretions.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Amikacin; Aminosalicylic Acid; Atazanavir Sulfate; Bedaquiline; Capreomycin; Clofazimine; Cobicistat; Contraceptive Agents; Contraceptives, Oral; Cycloserine; Darunavir; Desogestrel; Dolutegravir; Efavirenz; Elvitegravir; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol valerate; Ethambutol; Ethinyl Estradiol; Ethionamide; Etonogestrel; Etravirine; Isoniazid; Kanamycin; Levofloxacin; Linezolid; Lopinavir; Moxifloxacin; Nevirapine; Norgestimate, ethinyl estradiol drug combination; Ofloxacin; Polyestradiol phosphate; Prothionamide; Pyrazinamide; Rifampin; Ritonavir; Tenofovir

Criteria

Maternal Inclusion Criteria:

• Participant must belong to one of the following 5 groups:

1. HIV-infected pregnant women greater than or equal to 20 weeks gestation NOT on TB treatment receiving one or more of the ARV drugs/drug combinations specified in the protocol

2. HIV-infected pregnant women greater than or equal to 20 weeks gestation receiving one of the ARV drugs/drug combinations specified in the protocol and TB treatment with at least one of the TB drugs, specified in the protocol, at study entry

3. HIV-uninfected pregnant women greater than or equal to 20 weeks gestation receiving at least two of the first-line TB drugs, specified in the protocol, at study entry

4. HIV-infected and HIV-uninfected pregnant women greater than or equal to 20 weeks gestation receiving at least two of the second-line TB drugs, specified in the protocol, at study entry

5. HIV-infected women 2 to 12 weeks (14 to 84 days) post-delivery receiving one of the ARV drug combinations listed in the protocol AND starting postpartum contraceptives as listed in the protocol

• The woman must be stable on the ARV drug/drug combination and/or TB drug combination for at least 2 weeks prior to PK sampling

• If a woman is receiving a specific generic ARV formulation, the protocol team has approved this formulation

• HIV-infected pregnant women must be planning to continue on current ARV regimen until postpartum PK sampling is completed. HIV-infected postpartum women on hormonal contraceptives must be planning to continue on ARV and contraceptive regimens until final PK sampling is completed.

• For HIV-infected women: confirmed HIV infection, documented by positive results from two samples collected at different time points prior to study entry. More information on this criterion can be found in the protocol.

• HIV-uninfected pregnant women must have documented negative HIV antibody test during current pregnancy. Note: adequate source documentation, including the date of specimen collection, date of testing, test performed, and test result, must be available.

• Participants enrolling in the 3rd trimester must enroll by 37 6/7 weeks gestation

• Participant can provide legal informed consent per local regulations

• If a woman has completed this study and becomes pregnant again, she may re-enroll in the study only if she is enrolled in a different arm than that studied during her initial enrollment

Maternal Exclusion Criteria:

• Women on medicines known to interfere with absorption, metabolism, or clearance of the drug being evaluated (see protocol for more information). Rifampicin is permitted for women being evaluated for TB and ARV drug interactions.

• If pregnant, carrying multiple fetuses

• Clinical or laboratory toxicity that, in the opinion of the site investigator, would be likely to require a change in the medicine regimen during the period of study

Infant Enrollment Criteria:

• All infants of mothers enrolled during pregnancy (meeting criteria specified above) are enrolled, in utero, immediately after maternal enrollment.

Infant Requirements for Washout Pharmacokinetic Sampling:

• Born to HIV-infected mother enrolled during pregnancy in an ARV arm (does not include infants born to HIV-uninfected mothers receiving TB drugs)

• Birth weight greater than 1000 grams

• Is NOT receiving disallowed medications described in Section 7 of the protocol

• Does not have any severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the site investigator

• Born after singleton delivery (not after multiple birth)