To determine what dosing regimen of atazanavir (ATV) / ritonavir (RTV) produces adequate drug exposure during pregnancy compared to drug exposure in historical data in human immunodeficiency virus (HIV) infected participants.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
69
Capsules, tablets, Oral, initially ATV 300 mg + RTV 100 mg + ZDV/3TC 300/150 mg, dose escalated to ATV 400 mg + RTV 100 mg + ZDV/3TC 300/150 mg, ATV and RTV once daily, lamivudine (ZDV) / zidovudine (3TC) twice daily (BID), up to 36 weeks
Triple O Medical Services, P.A.
West Palm Beach, Florida, United States
Women's Hospital Of Texas
Houston, Texas, United States
Local Institution
San Juan, Puerto Rico
Local Institution
Soweto, Gauteng, South Africa
Infant Gestational Age at Delivery
Time frame: At the time of delivery
Infant Gender
Time frame: At the time of delivery
Infant Race
Time frame: At the time of delivery
Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval
Cmax = maximum observed plasma concentration of atazanavir at specified time points.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval
Cmax = maximum observed plasma concentration of ritonavir at specified time points.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
Mean ATV Area Under the Concentration Curve (AUC TAU)
AUC = area under the concentration curve (AUC \[TAU\]) of atazanavir in one dosing interval from time zero to 24 hours.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
Mean RTV Area Under the Concentration Curve (AUC TAU)
AUC = area under the concentration curve (AUC \[TAU\]) of ritonavir in one dosing interval.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose
Cmin = plasma concentration 24 hours post dose of atazanavir at specified time points.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Local Institution
Sunnyside, Gauteng, South Africa
Local Institution
Westdene, Gauteng, South Africa
Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose
Cmin = plasma concentration 24 hours post dose of ritonavir at specified time points.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose.
Mean ATV Terminal Elimination Half Life (T 1/2)
T 1/2 = terminal elimination half life of atazanavir at specified time points.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
Mean RTV Terminal Elimination Half Life (T 1/2)
T 1/2 = terminal elimination half life of ritonavir at specified time points.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
Mean ATV Time of Maximum Observed Plasma Concentration (Tmax)
Tmax = time to reach maximum observed plasma concentration of atazanavir at specified time points.
Time frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum
Mean RTV Time of Maximum Observed Plasma Concentration (Tmax)
Tmax = time to reach the maximum observed plasma concentration of ritonavir at specified time points.
Time frame: Pregnancy Weeks 12 to 28, Weeks 28 to 36, and 4-6 Weeks Postpartum
Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery
The maternal HIV RNA level is assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.
Time frame: Day of Delivery ± 2 Days
Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level
The maternal HIV RNA level was determined at baseline and the day of delivery ± 2 days using VR-OC. The maternal HIV RNA level is assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.
Time frame: Baseline, Day of Delivery ± 2 Days
Mean HIV RNA Level at Baseline
Time frame: Baseline
Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count
The median CD4 cell count change from baseline was calculated for all treated mothers at the time of delivery ± 2 days. Maternal CD4 cell counts were assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.
Time frame: Baseline, Day of Delivery ± 2 Days
Mean CD4 Cell Count at Baseline
Time frame: Baseline
Infant HIV Status
The neonatal HIV-1 status are assessed by the Roche Amplicor HIV-1 DNA Assay Version 1.5 (Roche Molecular Systems).
Time frame: Birth Through 6 Months on Study
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE =any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time frame: During study period and 30 days post-study.
Number of Participants With Grade 2 to Grade 4 AEs and SAEs
AEs and SAEs considered possibly, probably, or certainly related to study treatment, were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). Hyperbilirubinemia (Grade 1=1.1 to 1.5 upper limit of normal \[ULN\] \[mild\], Grade 2=1.6 to 2.5 ULN \[moderate\], Grade 3=2.6 to 5.0 ULN \[severe\], Grade 4= \> 5.0 ULN \[potentially life threatening\]).
Time frame: During Study Period and 30 Days Post-Study.
SAEs in Enrolled Mothers
SAEs were evaluated for all treated and untreated participants. An SAE was defined as an untoward medical occurrence that results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event); might have caused death if it were more severe, required inpatient hospitalization or prolongation of existing hospitalization, in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, an important medical event that required intervention to prevent serious outcomes.
Time frame: During Study Period and 30 Days Post-Study.
SAEs in Enrolled Infants
SAEs were evaluated for all treated and untreated participants. An SAE was defined as an untoward medical occurrence that results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event); might have caused death if it were more severe, required inpatient hospitalization or prolongation of existing hospitalization, in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, an important medical event that required intervention to prevent serious outcomes.
Time frame: Birth Through Week 16 of Life
Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration
Mean atazanavir maternal plasma concentration and neonatal cord blood concentration as measured at the time of delivery.
Time frame: At Time of Delivery
Median Infant Total Bilirubin Level
Median infant total bilirubin level as measured at specified time points.
Time frame: Birth (Day 1), Day 3, Day 5, and Day 7 of Life
Mean Atazanavir Plasma Protein Binding
Atazanavir Plasma Protein Binding Percentage measured at specified time points.
Time frame: Pregnancy Weeks 28 to Delivery at 3 Hours Postdose and 24 Hours Postdose, and Time of Delivery
Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose
The MACS was administered to evaluate participant adherence to each drug and the adherence to the regimen. The MACS adherence questionnaire asks patients how many medication doses they missed during the previous day, 2 days, 3 days and 4 days. Drug-specific questions included adherence with dose and frequency. Adherence was defined as taking all doses and numbers of pills as prescribed for each medication. This strict adherence cut-off was based on the guidelines stating that anything less than excellent adherence may result in a virus breakthrough and development of resistance.
Time frame: Study Week 2, Pregnancy Weeks 20 to Weeks 28, Pregnancy Weeks 28 to Delivery, Week 2 Postpartum, Week 4 Postpartum