Pharmacokinetics of Atazanavir/Ritonavir in HIV-1 Infected Pregnant Women

Cmax = maximum observed plasma concentration of atazanavir at specified time points.

Cmax = maximum observed plasma concentration of ritonavir at specified time points.

AUC = area under the concentration curve (AUC [TAU]) of atazanavir in one dosing interval from time zero to 24 hours.

AUC = area under the concentration curve (AUC [TAU]) of ritonavir in one dosing interval.

Cmin = plasma concentration 24 hours post dose of atazanavir at specified time points.

Cmin = plasma concentration 24 hours post dose of ritonavir at specified time points.

T 1/2 = terminal elimination half life of atazanavir at specified time points.

T 1/2 = terminal elimination half life of ritonavir at specified time points.

Tmax = time to reach maximum observed plasma concentration of atazanavir at specified time points.

Tmax = time to reach the maximum observed plasma concentration of ritonavir at specified time points.

The maternal HIV RNA level is assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.

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.

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.

The neonatal HIV-1 status are assessed by the Roche Amplicor HIV-1 DNA Assay Version 1.5 (Roche Molecular Systems).

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.

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]).

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.

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.

Mean atazanavir maternal plasma concentration and neonatal cord blood concentration as measured at the time of delivery.

Median infant total bilirubin level as measured at specified time points.

Atazanavir Plasma Protein Binding Percentage measured at specified time points.

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.