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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT00326716

First received: May 15, 2006

Last updated: November 4, 2011

Last verified: November 2011

History of Changes

Results First Received: January 5, 2011

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Pharmacokinetics Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	HIV Infection
Intervention:	Drug: Atazanavir + Ritonavir + Combivir

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Pregnant participants were enrolled at 6 sites: United States (2), South Africa (3), and Puerto Rico (1).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 69 enrolled participants, 28 mothers were not treated. Failure to continue to meet enrollment criteria resulting in discontinuation in 24/28 participants and 4 were not treated: 1 poor/no compliance, 1 met exclusion criteria, 1 was ARV naive subject with HIV RNA < 400 c/mL, and 1 was unable to comply with study procedures.

Reporting Groups

	Description
Mother ATV 300 mg / RTV 100 mg	Mothers receiving atazanavir (ATV) / ritonavir (RTV) 300/100 mg once daily (QD) + lamivudine (ZDV) / zidovudine (3TC) 300/150 mg twice daily (BID) during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Infants ATV 300 mg / RTV 100 mg	Infants born to mothers receiving treatment with ATV 300 mg / RTV 100 mg during the third trimester of pregnancy.
Infants ATV 400 mg / RTV 100 mg	Infants born to mothers receiving treatment with ATV 400 mg / RTV 100 mg during the third trimester of pregnancy.

Participant Flow for 2 periods

Period 1: Pre-Natal Mothers

	Mother ATV 300 mg / RTV 100 mg	Mother ATV 400 mg / RTV 100 mg	Infants ATV 300 mg / RTV 100 mg	Infants ATV 400 mg / RTV 100 mg
STARTED	20	21	0	0
COMPLETED	19 ^[1]	19 ^[1]	0 ^[2]	0 ^[2]
NOT COMPLETED	1	2	0	0
Discontinued ATV Before Delivery	1	2	0	0

[1]	Completion was defined as completing the study.
[2]	Completion was defined as completing all follow up visits through 6 months.

Period 2: Infants

	Infants ATV 300 mg / RTV 100 mg	Infants ATV 400 mg / RTV 100 mg
STARTED	20 ^[1]	20 ^[2]
COMPLETED	20	20
NOT COMPLETED	0	0

[1]	All infants were followed.
[2]	All infants were followed. One mother withdrew consent pre-delivery and her infant was not followed.

Baseline Characteristics

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Reporting Groups

	Description
Mother ATV 300 mg / RTV 100 mg	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Total	Total of all reporting groups

Baseline Measures

	Mother ATV 300 mg / RTV 100 mg	Mother ATV 400 mg / RTV 100 mg	Total
Number of Participants [units: participants]	20	21	41
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	20	21	41
>=65 years	0	0	0
Age [units: Years] Median ( Full Range )	29 ( 21 to 38 )	28 ( 19 to 37 )	28 ( 19 to 38 )
Gender [units: participants]
Female	20	21	41
Male	0	0	0
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	17	19	36
White	3	1	4
More than one race	0	1	1
Unknown or Not Reported	0	0	0
Region of Enrollment [units: participants]
North America	6	6	12
Africa	14	15	29
HIV RNA Distribution at Baseline [units: c/mL]
<50	3	1	4
50 to < 30,000	13	13	26
30,000 to < 100,000	3	6	9
>= 100,000	1	1	2
Infant Gestational Age at Delivery [units: Weeks] Median ( Full Range )	38 ( 35 to 40 )	38 ( 35 to 41 )	38 ( 35 to 41 )

Outcome Measures

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1. Primary:

Infant Gestational Age at Delivery [ Time Frame: At the time of delivery ]

Measure Type	Primary
Measure Title	Infant Gestational Age at Delivery
Measure Description	No text entered.
Time Frame	At the time of delivery
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All infants.

Reporting Groups

	Description
Mothers ATV 300 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 38 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / 100 mg Third Trimester	Mothers ATV 400 mg / 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	20	20
Infant Gestational Age at Delivery [units: Weeks] Mean ± Standard Error	38 ± 0.3	38 ± 0.3

No statistical analysis provided for Infant Gestational Age at Delivery

2. Primary:

Infant Gender [ Time Frame: At the time of delivery ]

Measure Type	Primary
Measure Title	Infant Gender
Measure Description	No text entered.
Time Frame	At the time of delivery
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All infants.

Reporting Groups

	Description
Mothers ATV 300 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 38 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / 100 mg Third Trimester	Mothers ATV 400 mg / 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	20	20
Infant Gender [units: Participants]
Male	12	9
Female	8	11

No statistical analysis provided for Infant Gender

3. Primary:

Infant Race [ Time Frame: At the time of delivery ]

Measure Type	Primary
Measure Title	Infant Race
Measure Description	No text entered.
Time Frame	At the time of delivery
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All infants.

Reporting Groups

	Description
Mothers ATV 300 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 38 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / 100 mg Third Trimester	Mothers ATV 400 mg / 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	20	20
Infant Race [units: Participants]
Black	15	18
White	5	1
Mixed Race	0	1

No statistical analysis provided for Infant Race

4. Primary:

Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]

Measure Type	Primary
Measure Title	Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the pharmacokinetic (PK) concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg once daily (QD) + ZDV/3TC 300/150 mg twice daily (BID) during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers ATV 400 mg / RTV 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval [units: ng / mL] Geometric Mean ( 95% Confidence Interval )	3,729.09 ( 2,744.17 to 5,067.52 )	3,291.46 ( 2,444.82 to 4,431.30 )	4,210.76 ( 3,369.46 to 5,262.11 )

No statistical analysis provided for Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval

5. Primary:

Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]

Measure Type	Primary
Measure Title	Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg once daily (QD) + ZDV/3TC 300/150 mg twice daily (BID) during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers ATV 400 mg / RTV 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval [units: ng / mL] Geometric Mean ( 95% Confidence Interval )	530.81 ( 333.20 to 845.61 )	587.36 ( 423.55 to 814.52 )	524.48 ( 368.76 to 745.95 )

No statistical analysis provided for Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval

6. Primary:

Mean ATV Area Under the Concentration Curve (AUC TAU) [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]

Measure Type	Primary
Measure Title	Mean ATV Area Under the Concentration Curve (AUC TAU)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg once daily (QD) + ZDV/3TC 300/150 mg twice daily (BID) during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers ATV 400 mg / RTV 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean ATV Area Under the Concentration Curve (AUC TAU) [units: ng•h / mL] Geometric Mean ( 95% Confidence Interval )	34,399.13 ( 25,975.68 to 45,554.15 )	34,251.50 ( 27,173.69 to 43,172.84 )	46,602.45 ( 36,445.75 to 59,589.63 )

No statistical analysis provided for Mean ATV Area Under the Concentration Curve (AUC TAU)

7. Primary:

Mean RTV Area Under the Concentration Curve (AUC TAU) [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]

Measure Type	Primary
Measure Title	Mean RTV Area Under the Concentration Curve (AUC TAU)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg once daily (QD) + ZDV/3TC 300/150 mg twice daily (BID) during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers ATV 400 mg / RTV 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean RTV Area Under the Concentration Curve (AUC TAU) [units: ng•h / mL] Geometric Mean ( 95% Confidence Interval )	4,500.03 ( 3,243.97 to 6,242.43 )	4,664.93 ( 3,670.14 to 5,929.35 )	4,383.30 ( 3,107.41 to 6,183.06 )

No statistical analysis provided for Mean RTV Area Under the Concentration Curve (AUC TAU)

8. Primary:

Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose. ]

Measure Type	Primary
Measure Title	Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose
Measure Description	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.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg once daily (QD) + ZDV/3TC 300/150 mg twice daily (BID) during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers ATV 400 mg / RTV 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose [units: ng•h / mL] Geometric Mean ( 95% Confidence Interval )	663.78 ( 492.65 to 894.35 )	668.48 ( 529.06 to 844.64 )	916.63 ( 665.77 to 1,262.02 )

No statistical analysis provided for Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose

9. Primary:

Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose. ]

Measure Type	Primary
Measure Title	Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose
Measure Description	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.
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg once daily (QD) + ZDV/3TC 300/150 mg twice daily (BID) during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg Second Trimester	Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers ATV 400 mg / RTV 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose [units: ng•h / mL] Geometric Mean ( 95% Confidence Interval )	50.10 ( 28.39 to 88.43 )	41.12 ( 29.06 to 58.21 )	38.05 ( 26.24 to 55.17 )

No statistical analysis provided for Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose

10. Primary:

Mean ATV Terminal Elimination Half Life (T 1/2) [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]

Measure Type	Primary
Measure Title	Mean ATV Terminal Elimination Half Life (T 1/2)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 38 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / 100 mg Second Trimester	Mothers ATV 300 mg / 100 mg Third Trimester	Mothers ATV 400 mg / 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean ATV Terminal Elimination Half Life (T 1/2) [units: Hours] Geometric Mean ( 95% Confidence Interval )	10.42 ( 9.14 to 11.89 )	12.10 ( 9.44 to 15.51 )	12.17 ( 10.42 to 14.21 )

No statistical analysis provided for Mean ATV Terminal Elimination Half Life (T 1/2)

11. Primary:

Mean RTV Terminal Elimination Half Life (T 1/2) [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]

Measure Type	Primary
Measure Title	Mean RTV Terminal Elimination Half Life (T 1/2)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set

Reporting Groups

	Description
Mothers ATV 300 mg / 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 38 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / 100 mg Second Trimester	Mothers ATV 300 mg / 100 mg Third Trimester	Mothers ATV 400 mg / 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean RTV Terminal Elimination Half Life (T 1/2) [units: Hours] Geometric Mean ( 95% Confidence Interval )	5.03 ( 4.51 to 5.60 )	5.28 ( 4.73 to 5.90 )	5.10 ( 4.30 to 6.05 )

No statistical analysis provided for Mean RTV Terminal Elimination Half Life (T 1/2)

12. Primary:

Mean ATV Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum ]

Measure Type	Primary
Measure Title	Mean ATV Time of Maximum Observed Plasma Concentration (Tmax)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 38 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / 100 mg Second Trimester	Mothers ATV 300 mg / 100 mg Third Trimester	Mothers ATV 400 mg / 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean ATV Time of Maximum Observed Plasma Concentration (Tmax) [units: Hours] Geometric Mean ( 95% Confidence Interval )	3.68 ( 2.92 to 4.64 )	2.94 ( 2.36 to 3.65 )	3.30 ( 2.57 to 4.23 )

No statistical analysis provided for Mean ATV Time of Maximum Observed Plasma Concentration (Tmax)

13. Primary:

Mean RTV Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Pregnancy Weeks 12 to 28, Weeks 28 to 36, and 4-6 Weeks Postpartum ]

Measure Type	Primary
Measure Title	Mean RTV Time of Maximum Observed Plasma Concentration (Tmax)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants in the PK concentration data set.

Reporting Groups

	Description
Mothers ATV 300 mg / 100 mg Second Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 12 to 28 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 300 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 38 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / 100 mg Second Trimester	Mothers ATV 300 mg / 100 mg Third Trimester	Mothers ATV 400 mg / 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	9	20	20
Mean RTV Time of Maximum Observed Plasma Concentration (Tmax) [units: Hours] Geometric Mean ( 95% Confidence Interval )	6.11 ( 3.81 to 9.80 )	4.15 ( 3.12 to 5.54 )	4.63 ( 3.45 to 6.19 )

No statistical analysis provided for Mean RTV Time of Maximum Observed Plasma Concentration (Tmax)

14. Secondary:

Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery [ Time Frame: Day of Delivery ± 2 Days ]

Measure Type	Secondary
Measure Title	Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery
Measure Description	The maternal HIV RNA level is assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.
Time Frame	Day of Delivery ± 2 Days
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis for the proportion of HIV RNA < 400 and < 50 c/mL at delivery is based on the Virologic Response - Observed Cases (VR-OC). VR-OC classifies subjects who remain on study therapy as responders according to a single HIV RNA measurement < 400 c/mL (or < 50 c/mL) closest to delivery and within delivery date ± 2 days.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 38 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg	Mothers ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	19	20
Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery [units: Participants]
HIV RNA < 400 copies/mL	19	20
HIV RNA < 50 copies/mL	19	19

No statistical analysis provided for Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery

15. Secondary:

Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level [ Time Frame: Baseline, Day of Delivery ± 2 Days ]

Measure Type	Secondary
Measure Title	Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The median maternal HIV RNA Level Change From Baseline was calculated for all treated mothers at the time of delivery. The maternal HIV RNA level at delivery was determined as the closest to delivery and within a pre-defined visit window for delivery, which is delivery date ± 2 days.

Reporting Groups

	Description
Mother ATV 300 mg / RTV 100 mg	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mother ATV 300 mg / RTV 100 mg	Mother ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	18	19
Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level [units: log10 c / mL] Median ( Inter-Quartile Range )	-1.8 ( -2.43 to -1.39 )	-2.37 ( -2.93 to -1.81 )

No statistical analysis provided for Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level

16. Secondary:

Mean HIV RNA Level at Baseline [ Time Frame: Baseline ]

Measure Type	Secondary
Measure Title	Mean HIV RNA Level at Baseline
Measure Description	No text entered.
Time Frame	Baseline
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All treated participants.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers ATV 400 mg / RTV 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	20	21
Mean HIV RNA Level at Baseline [units: log10 cm / mL] Mean ± Standard Error	3.520 ± 0.232	4.020 ± 0.171

No statistical analysis provided for Mean HIV RNA Level at Baseline

17. Secondary:

Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count [ Time Frame: Baseline, Day of Delivery ± 2 Days ]

Measure Type	Secondary
Measure Title	Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The median CD4 Cell Count Change From Baseline was calculated based on all treated mothers. The maternal CD4 cell count at delivery was determined as the closest to delivery and within a pre-defined visit window for delivery, which is delivery date ± 2 days.

Reporting Groups

	Description
Mother ATV 300 mg / RTV 100 mg	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mother ATV 300 mg / RTV 100 mg	Mother ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	17	20
Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count [units: cells / mm^3] Median ( Inter-Quartile Range )	89 ( -75 to 213 )	174 ( -39 to 257 )

No statistical analysis provided for Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count

18. Secondary:

Mean CD4 Cell Count at Baseline [ Time Frame: Baseline ]

Measure Type	Secondary
Measure Title	Mean CD4 Cell Count at Baseline
Measure Description	No text entered.
Time Frame	Baseline
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All treated participants.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg Third Trimester	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during weeks 28 to 36 of pregnancy. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg Third Trimester	Mothers ATV 400 mg / RTV 100 mg Third Trimester
Number of Participants Analyzed [units: participants]	20	21
Mean CD4 Cell Count at Baseline [units: cells / mm^3] Mean ± Standard Error	435.0 ± 39.2	390.0 ± 25.0

No statistical analysis provided for Mean CD4 Cell Count at Baseline

19. Secondary:

Infant HIV Status [ Time Frame: Birth Through 6 Months on Study ]

Measure Type	Secondary
Measure Title	Infant HIV Status
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All infants.

Reporting Groups

	Description
Infant ATV 300 mg / RTV 100 mg	No text entered.
Infant ATV 400 mg / RTV 100 mg	No text entered.

Measured Values

	Infant ATV 300 mg / RTV 100 mg	Infant ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	20	20
Infant HIV Status [units: Participants]
HIV Positive	0	0
HIV Negative	20	20

No statistical analysis provided for Infant HIV Status

20. Secondary:

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: During study period and 30 days post-study. ]

Measure Type	Secondary
Measure Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measure Description	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.
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The number of SAEs is based on enrolled participants. Data were pooled from the ATV 300 mg / RTV 100 mg and ATV 400 mg / RTV 100 mg groups for all treated mothers and all infants.

Reporting Groups

	Description
All Treated Mothers	Data are pooled for mothers in the ATV 300 mg / RTV 100 mg and the ATV 400 mg / 100 mg groups.
All Infants	Data are pooled for infants in the ATV 300 mg / RTV 100 mg and the ATV 400 mg / 100 mg groups.

Measured Values

	All Treated Mothers	All Infants
Number of Participants Analyzed [units: participants]	41	40
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [units: Participants]
Death (n=41, n=40)	0	0
Serious Adverse Event (n=41, n=40)	16	14
Total AEs Leading to Discontinuation (n=41, n=40)	2	2
Anemia Leading to Discontinuation (n=41, n=40)	1	2
Transaminitis Discontinuation (n=41, n=40)	1	0
Prematurity Causing Discontinuation (n=41, n=40)	NA ^[1]	1
All AEs (n=41, n=40)	40	40
Anemia (n=41, n=40)	6	3
Diarrhea (n=41, n=40)	4	4
Nausea (n=41, n=40)	6	0
Vomiting (n=41, n=40)	7	5
Jaundice (n=41, n=40)	10	20
Hyperbilirubinemia (n=41, n=40)	1	1
Ocular Icterus (n=41, n=40)	3	0
Skin / subcutaneous tissue disorders (n=41, n=40)	10	20

[1]	Prematurity causing discontinuation was considered an infant only AE/SAE and thus was not deemed appropriate for evaluation in the mothers only population.

No statistical analysis provided for Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

21. Secondary:

Number of Participants With Grade 2 to Grade 4 AEs and SAEs [ Time Frame: During Study Period and 30 Days Post-Study. ]

Measure Type	Secondary
Measure Title	Number of Participants With Grade 2 to Grade 4 AEs and SAEs
Measure Description	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.
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data were pooled from the ATV 300 mg / RTV 100 mg and ATV 400 mg / RTV 100 mg groups for all treated mothers and all infants. The number of AEs and SAEs is based on enrolled participants.

Reporting Groups

	Description
All Treated Mothers	Data are pooled for mothers in the ATV 300 mg / RTV 100 mg and the ATV 400 mg / 100 mg groups.
All Infants	Data are pooled for infants in the ATV 300 mg / RTV 100 mg and the ATV 400 mg / 100 mg groups.

Measured Values

	All Treated Mothers	All Infants
Number of Participants Analyzed [units: participants]	41	40
Number of Participants With Grade 2 to Grade 4 AEs and SAEs [units: Participants]
Grade 2 to Grade 4 (n=41, n=40)	32	19
Related Grade 2 to Grade 4 (n=41, n=40)	10	0
Grade 3 to Grade 4 (n=41, n=40)	12	8
Grade 3 to Grade 4 Total Bilirubin (n=41, n=40)	19	7

No statistical analysis provided for Number of Participants With Grade 2 to Grade 4 AEs and SAEs

22. Secondary:

SAEs in Enrolled Mothers [ Time Frame: During Study Period and 30 Days Post-Study. ]

Measure Type	Secondary
Measure Title	SAEs in Enrolled Mothers
Measure Description	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.
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data were analyzed for all treated and untreated mothers.

Reporting Groups

	Description
Mother ATV 300 mg / RTV 100 mg	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mother ATV 300 mg / RTV 100 mg	Mother ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	20	21
SAEs in Enrolled Mothers [units: Participants]
Any Adverse Experience	7	8
Blood and Lymphatic System Disorders	1	2
Anemia	1	2
Cardiac Disorders	1	1
Cardiomyopathy	1	0
Sinus Arrhythmia	0	1
Gastrointestinal Disorders	0	1
Abdominal Hernia	0	1
Hepatobiliary Disorders	0	1
Hyperbilirubinemia	0	1
Infections and Infestations	2	2
Endometrial Decidual	2	0
Pneumonia	0	1
Sepsis	0	1
Investigations	0	1
Transaminases Increased	0	1
Pregnancy, Puerperium, and Perinatal Conditions	2	2
Amenorrhea	0	1
Pre-eclampsia	1	1
Pregnancy Induced Hypertension	0	0
Premature Rupture of Membranes	1	0
Vascular Disorders	1	1
Hypertension	0	1
Hemorrhage	1	0

No statistical analysis provided for SAEs in Enrolled Mothers

23. Secondary:

SAEs in Enrolled Infants [ Time Frame: Birth Through Week 16 of Life ]

Measure Type	Secondary
Measure Title	SAEs in Enrolled Infants
Measure Description	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
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
SAEs were recorded for all enrolled infants.

Reporting Groups

	Description
Infant ATV 300 mg / RTV 100 mg	Infants of mothers taking ATV 300 mg / RTV 100 mg at birth.
Infant ATV 400 mg / RTV 100 mg	Infants of mothers taking ATV 400 mg / RTV 100 mg at birth.

Measured Values

	Infant ATV 300 mg / RTV 100 mg	Infant ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	20	20
SAEs in Enrolled Infants [units: Participants]
Any Adverse Experience	10	4
Blood and Lymphatic System Disorders	1	1
Anemia	1	1
Cardiac Disorders	1	0
Cardio-Respiratory Arrest	1	0
Restrictive Cardiomyopathy	1	0
Congenital, Familial, and Genetic Disorders	0	1
Atrial Septal Defect	0	1
Gastrointestinal Disorders	1	0
Constipation	1	0
Vomiting	1	0
Hepatobiliary Disorders	1	1
Hyperbilirubinemia	0	1
Jaundice	1	0
Infections and Infestations	4	2
Bronchiolitis	0	2
Gastroenteritis	1	0
Meningitis	1	0
Pneumonia	0	1
Sepsis	1	0
Syphilis	1	0
Injury, Poisoning, and Procedural Complications	1	0
Overdose	1	0
Metabolism and Nutrition Disorders	1	1
Hyperkalemia	1	0
Hypoglycemia	0	1
Nervous System Disorders	1	0
Cerebral Ischemia	1	0
Convulsion	1	0
Pregnancy, Puerperium, and Perinatal Conditions	1	1
Premature Baby	1	1
Respiratory, Thoracic, and Mediastinal Disorders	2	0
Neonatal Respiratory Distress Syndrome	1	0
Respiratory Distress	1	0

No statistical analysis provided for SAEs in Enrolled Infants

24. Secondary:

Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration [ Time Frame: At Time of Delivery ]

Measure Type	Secondary
Measure Title	Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration
Measure Description	Mean atazanavir maternal plasma concentration and neonatal cord blood concentration as measured at the time of delivery.
Time Frame	At Time of Delivery
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Mothers ATV 300 mg / RTV 100 mg	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID at the time of delivery. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mothers ATV 400 mg / RTV 100 mg	Infants born to mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID at the time of delivery. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mothers ATV 300 mg / RTV 100 mg	Mothers ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	20	21
Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration [units: ng / mL] Mean ± Standard Deviation
Maternal Serum Concentration	1,412.05 ± 888.85	1,568.06 ± 846.44
Cord Blood Concentration	273.20 ± 182.04	231.49 ± 158.29

No statistical analysis provided for Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration

25. Secondary:

Median Infant Total Bilirubin Level [ Time Frame: Birth (Day 1), Day 3, Day 5, and Day 7 of Life ]

Measure Type	Secondary
Measure Title	Median Infant Total Bilirubin Level
Measure Description	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
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Infant ATV 300 mg / RTV 100 mg	Infants of mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Infant ATV 400 mg / RTV 100 mg	Infansts of mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Infant ATV 300 mg / RTV 100 mg	Infant ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	20	20
Median Infant Total Bilirubin Level [units: mg / dL] Median ( Inter-Quartile Range )
Day 1 (Birth)	3.20 ( 2.80 to 4.30 )	3.25 ( 2.80 to 4.40 )
Day 3	8.40 ( 5.40 to 11.30 )	9.20 ( 7.00 to 9.60 )
Day 5	7.10 ( 3.05 to 10.20 )	9.25 ( 5.50 to 10.45 )
Day 7	5.10 ( 1.90 to 8.90 )	7.30 ( 2.50 to 9.30 )

No statistical analysis provided for Median Infant Total Bilirubin Level

26. Secondary:

Mean Atazanavir Plasma Protein Binding [ Time Frame: Pregnancy Weeks 28 to Delivery at 3 Hours Postdose and 24 Hours Postdose, and Time of Delivery ]

Measure Type	Secondary
Measure Title	Mean Atazanavir Plasma Protein Binding
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Mother ATV 300 mg / RTV 100 mg	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mother ATV 300 mg / RTV 100 mg	Mother ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	20	21
Mean Atazanavir Plasma Protein Binding [units: Percentage Bound] Mean ± Standard Deviation
Third Trimester 3 Hours Post Dose (n = 20, 20)	91.34 ± 2.32	87.70 ± 2.69
Third Trimester 24 Hours Post Dose (n = 19, 20)	90.37 ± 2.58	88.89 ± 2.40
Time of Delivery (n = 15, 12)	77.05 ± 6.88	75.62 ± 4.34

No statistical analysis provided for Mean Atazanavir Plasma Protein Binding

27. Secondary:

Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose [ Time Frame: Study Week 2, Pregnancy Weeks 20 to Weeks 28, Pregnancy Weeks 28 to Delivery, Week 2 Postpartum, Week 4 Postpartum ]

Measure Type	Secondary
Measure Title	Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All treated participants were included in this evaluation.

Reporting Groups

	Description
Mother ATV 300 mg / RTV 100 mg	Mothers receiving ATV/RTV 300/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.
Mother ATV 400 mg / RTV 100 mg	Mothers receiving ATV/RTV 400/100 mg QD + ZDV/3TC 300/150 mg BID during the third trimester. Each dose of ATV/RTV (taken with a light meal or snack) was taken approximately 24 hours apart. Each dose of ZDV/3TC (taken with or without food) was taken approximately 12 hours apart.

Measured Values

	Mother ATV 300 mg / RTV 100 mg	Mother ATV 400 mg / RTV 100 mg
Number of Participants Analyzed [units: participants]	20	21
Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose [units: Participants]
Study Week 2 Regimen (n = 20,18)	20	17
Study Week 2 ATV (n = 20,18)	20	17
Study Week 2 RTV (n = 20,18)	20	17
Study Week 2 ZDV/3TC (n = 20,18)	20	17
Visit 1 Pregnancy Week 20 to 28 Regimen (n=12, 9)	11	8
Visit 1 Pregnancy Week 20 to 28 ATV (n=12, 9)	12	8
Visit 1 Pregnancy Week 20 to 28 RTV (n=12, 9)	12	9
Visit 1 Pregnancy Week 20 to 28 ZDV/3TC (n=12, 9)	11	9
Visit 2 Pregnancy Week 20 to 28 Regimen (n=8, 5)	3	3
Visit 2 Pregnancy Week 20 to 28 ATV (n=8, 5)	8	5
Visit 2 Pregnancy Week 20 to 28 RTV (n=8, 5)	7	4
Visit 2 Pregnancy Week 20 to 28 ZDV/3TC (n=8, 5)	4	4
Visit 3 Pregnancy Week 20 to 28 Regimen (n=6, 2)	4	2
Visit 3 Pregnancy Week 20 to 28 ATV (n=6, 2)	5	2
Visit 3 Pregnancy Week 20 to 28 RTV (n=6, 2)	5	2
Visit 3 Pregnancy Week 20 to 28 ADV/3TC (n=6, 2)	4	2
Visit 4 Pregnancy Wk 20 to 28 Regimen (n=0, 13)	NA ^[1]	13
Visit 4 Pregnancy Week 20 to 28 ATV (n=0, 13)	NA ^[1]	13
Visit 4 Pregnancy Week 20 to 28 RTV (n=0, 13)	NA ^[1]	13
Visit 4 Pregnancy Wk 20 to 28 ZDV/3TC (n=0, 13)	NA ^[1]	13
Visit 1 Pregnancy Wk 20 to Birth Regimen (n=20,20)	19	20
Visit 1 Pregnancy Week 20 to Birth ATV (n=20,20)	20	20
Visit 1 Pregnancy Week 20 to Birth RTV (n=20,20)	20	20
Visit 1 Pregnancy Wk 20 to Birth ZDV/3TC (n=20,20)	19	20
Visit 2 Pregnancy Wk 20 to Birth Regimen (n=19,19)	18	18
Visit 2 Pregnancy Week 20 to Birth ATV (n=19,19)	19	19
Visit 2 Pregnancy Week 20 to Birth RTV (n=19,19)	19	19
Visit 2 Pregnancy Wk 20 to Birth ZDV/3TC (n=19,19)	18	18
Visit 3 Pregnancy Wk 20 to Birth Regimen (n=15,19)	12	18
Visit 3 Pregnancy Week 20 to Birth ATV (n=15,19)	13	19
Visit 3 Pregnancy Week 20 to Birth RTV (n=15,19)	13	19
Visit 3 Pregnancy Wk 20 to Birth ZDV/3TC (n=15,19)	12	18
Visit 4 Pregnancy Wk 28 to Birth Regimen (n=5,15)	5	15
Visit 4 Pregnancy Week 28 to Birth ATV (n=5,15)	5	15
Visit 4 Pregnancy Week 28 to Birth RTV (n=5,15)	5	15
Visit 4 Pregnancy Wk 28 to Birth ZDV/3TC (n=5,15)	5	15
Visit 5 Pregnancy Wk 28 to Birth Regimen (n=1, 2)	1	2
Visit 5 Pregnancy Week 28 to Birth ATV (n=1, 2)	1	2
Visit 5 Pregnancy Week 28 to Birth RTV (n=1, 2)	1	2
Visit 5 Pregnancy Wk 28 to Birth ZDV/3TC (n=1, 2)	1	2
Visit 6 Pregnancy Wk 28 to Birth Regimen (n=0, 1)	NA ^[2]	1
Visit 6 Pregnancy Week 28 to Birth ATV (n=0, 1)	NA ^[2]	1
Visit 6 Pregnancy Week 28 to Birth RTV (n=0, 1)	NA ^[2]	1
Visit 6 Pregnancy Wk 28 to Birth ZDV/3TC (n=0, 1)	NA ^[2]	1
Postpartum Week 2 Regimen (n=19, 19)	14	18
Postpartum Week 2 ATV (n=18, 19)	16	18
Postpartum Week 2 RTV (n=18, 19)	16	18
Postpartum Week 2 ZDV/3TC (n =19, 19)	14	18
Postpartum Week 4 Regimen (n=17, 19)	16	18
Postpartum Week 4 ATV (n=17, 19)	17	19
Postpartum Week 4 RTV (n=17, 19)	16	19
Postpartum Week 4 ZDV/3TC (n=17, 19)	17	18

[1]	Participants were titrated to the ATV 400 mg / RTV 100 mg prior to this visit and thus data are not available for this dosing group.
[2]	Participants experienced a dose escalation from ATV 300 mg / RTV 100 mg to ATV 400 mg / RTV 100 mg in the third trimester and thus this value was not calculated.

No statistical analysis provided for Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: clinical.trials@bms.com

No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Conradie F, Zorrilla C, Josipovic D, Botes M, Osiyemi O, Vandeloise E, Eley T, Child M, Bertz R, Hu W, Wirtz V, McGrath D. Safety and exposure of once-daily ritonavir-boosted atazanavir in HIV-infected pregnant women. HIV Med. 2011 Oct;12(9):570-9. Epub 2011 May 16.

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00326716 History of Changes
Other Study ID Numbers:	AI424-182
Study First Received:	May 15, 2006
Results First Received:	January 5, 2011
Last Updated:	November 4, 2011
Health Authority:	United States: Food and Drug Administration Republic of South Africa: National Ministry of Health

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