Overview

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)