The primary objective of this study is to evaluate the steady state pharmacokinetics of bictegravir (BIC) and confirm the dose of BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed pregnant women in their second and third trimesters.
Name: B/F/TAF
Description: 50/200/25 mg FDC tablet administered orally once daily without regard to foodType: DrugB/F/TAF
Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Measure: Pharmacokinetic (PK) Parameter: AUCtau of BIC Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Measure: PK Parameter: AUCtau of emtricitabine (FTC) and tenofovir alafenamide (TAF) Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Measure: PK Parameter: AUClast of BIC, FTC, and TAF Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: Cmax is defined as the maximum observed concentration of drug during the dosing interval.
Measure: PK Parameter: Cmax of BIC, FTC, and TAF Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: Ctau is defined as the observed drug concentration at the end of the dosing interval.
Measure: PK Parameter: Ctau of BIC and FTC Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: Clast is defined as the last observable concentration of drug.
Measure: PK Parameter: Clast of BIC, FTC, and TAF Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: Tmax is defined as the time (observed time point) of Cmax.
Measure: PK Parameter: Tmax of BIC, FTC, and TAF Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Measure: PK Parameter: t1/2 of BIC, FTC, and TAF Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: CL/F is defined as the apparent oral clearance following administration of the drug.
Measure: PK Parameter: CL/F of BIC, FTC, and TAF Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: Vz/F is defined as the apparent volume of distribution of the drug.
Measure: PK Parameter: Vz/F of BIC, FTC, and TAF Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseDescription: λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
Measure: PK Parameter: λz of BIC, FTC, and TAF Time: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdoseSingle Group Assignment
There are 2 SNPs
Key Inclusion Criteria: - The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures - With singleton pregnancy, at least 12 weeks but not more than 31 weeks pregnant at the time of screening - Agree not to breastfeed for the duration of the study - Currently on a stable antiretroviral regimen for ≥ 6 months preceding the screening visit - Documented plasma HIV-1 RNA levels of < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at the screening visit - Have no documented or suspected resistance to FTC, Tenofovir (TFV), or integrase strand-transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R or M184V/I - Historic genotype reports will be collected if available - Have a normal ultrasound, completed locally prior to the Day 1 visit, with no evidence of any fetal malformation or structural abnormality affecting either fetus or placenta - Normal maternal alfa-fetoprotein level at the screening visit Key Exclusion Criteria: - Have chronic hepatitis B virus (HBV) - Have active hepatitis C virus (HCV) infection - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening Note: Other protocol defined Inclusion/Exclusion criteria may apply. --- K65R ---
Key Inclusion Criteria: - The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures - With singleton pregnancy, at least 12 weeks but not more than 31 weeks pregnant at the time of screening - Agree not to breastfeed for the duration of the study - Currently on a stable antiretroviral regimen for ≥ 6 months preceding the screening visit - Documented plasma HIV-1 RNA levels of < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at the screening visit - Have no documented or suspected resistance to FTC, Tenofovir (TFV), or integrase strand-transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R or M184V/I - Historic genotype reports will be collected if available - Have a normal ultrasound, completed locally prior to the Day 1 visit, with no evidence of any fetal malformation or structural abnormality affecting either fetus or placenta - Normal maternal alfa-fetoprotein level at the screening visit Key Exclusion Criteria: - Have chronic hepatitis B virus (HBV) - Have active hepatitis C virus (HCV) infection - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening Note: Other protocol defined Inclusion/Exclusion criteria may apply. --- K65R --- --- M184V ---