Pharmacokinetics of Atazanavir/Ritonavir in HIV-1 Infected Pregnant Women
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00326716
Collaborator
(none)
69
6
1
38
11.5
0.3
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
69 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Study of the Pharmacokinetics of Atazanavir (ATV)/Ritonavir(RTV) Administered as Part of Highly Active Antiretroviral Therapy (HAART) in HIV-1 Infected Pregnant Women
Study Start Date
:
Jun 1, 2006
Actual Primary Completion Date
:
Jan 1, 2009
Actual Study Completion Date
:
Aug 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment
|
Drug: Atazanavir + Ritonavir + Combivir
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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Infant Gestational Age at Delivery [At the time of delivery]
- Infant Gender [At the time of delivery]
- Infant Race [At the time of delivery]
- Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum]
Cmax = maximum observed plasma concentration of atazanavir at specified time points.
- Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum]
Cmax = maximum observed plasma concentration of ritonavir at specified time points.
- Mean ATV Area Under the Concentration Curve (AUC TAU) [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum]
AUC = area under the concentration curve (AUC [TAU]) of atazanavir in one dosing interval from time zero to 24 hours.
- Mean RTV Area Under the Concentration Curve (AUC TAU) [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum]
AUC = area under the concentration curve (AUC [TAU]) of ritonavir in one dosing interval.
- Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose.]
Cmin = plasma concentration 24 hours post dose of atazanavir at specified time points.
- Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum at 24 hours following the daily dose.]
Cmin = plasma concentration 24 hours post dose of ritonavir at specified time points.
- Mean ATV Terminal Elimination Half Life (T 1/2) [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum]
T 1/2 = terminal elimination half life of atazanavir at specified time points.
- Mean RTV Terminal Elimination Half Life (T 1/2) [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum]
T 1/2 = terminal elimination half life of ritonavir at specified time points.
- Mean ATV Time of Maximum Observed Plasma Concentration (Tmax) [Pregnancy Weeks 12 to 28, 28 to 36, and 4-6 Weeks Postpartum]
Tmax = time to reach maximum observed plasma concentration of atazanavir at specified time points.
- Mean RTV Time of Maximum Observed Plasma Concentration (Tmax) [Pregnancy Weeks 12 to 28, Weeks 28 to 36, and 4-6 Weeks Postpartum]
Tmax = time to reach the maximum observed plasma concentration of ritonavir at specified time points.
Secondary Outcome Measures
- Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery [Day of Delivery ± 2 Days]
The maternal HIV RNA level is assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5.
- Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level [Baseline, Day of Delivery ± 2 Days]
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.
- Mean HIV RNA Level at Baseline [Baseline]
- Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count [Baseline, Day of Delivery ± 2 Days]
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.
- Mean CD4 Cell Count at Baseline [Baseline]
- Infant HIV Status [Birth Through 6 Months on Study]
The neonatal HIV-1 status are assessed by the Roche Amplicor HIV-1 DNA Assay Version 1.5 (Roche Molecular Systems).
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [During study period and 30 days post-study.]
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.
- Number of Participants With Grade 2 to Grade 4 AEs and SAEs [During Study Period and 30 Days Post-Study.]
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 in Enrolled Mothers [During Study Period and 30 Days Post-Study.]
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 in Enrolled Infants [Birth Through Week 16 of Life]
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 [At Time of Delivery]
Mean atazanavir maternal plasma concentration and neonatal cord blood concentration as measured at the time of delivery.
- Median Infant Total Bilirubin Level [Birth (Day 1), Day 3, Day 5, and Day 7 of Life]
Median infant total bilirubin level as measured at specified time points.
- Mean Atazanavir Plasma Protein Binding [Pregnancy Weeks 28 to Delivery at 3 Hours Postdose and 24 Hours Postdose, and Time of Delivery]
Atazanavir Plasma Protein Binding Percentage measured at specified time points.
- Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose [Study Week 2, Pregnancy Weeks 20 to Weeks 28, Pregnancy Weeks 28 to Delivery, Week 2 Postpartum, Week 4 Postpartum]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
HIV-infected pregnant women
-
18 years of age
-
Between week 12 and 32 gestation
-
CD4 > 200 cells/mm³
-
Treatment-naive with HIV RNA > 400 c/mL, on HAART with HIV RNA <50 c/mL, or previously treated with ATV (< 3 weeks) with HIV RNA>400 c/mL
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Triple O Medical Services, P.A. | West Palm Beach | Florida | United States | 33401 |
| 2 | Women's Hospital Of Texas | Houston | Texas | United States | 77054 |
| 3 | Local Institution | San Juan | Puerto Rico | 00936 | |
| 4 | Local Institution | Soweto | Gauteng | South Africa | 2001 |
| 5 | Local Institution | Sunnyside | Gauteng | South Africa | 0002 |
| 6 | Local Institution | Westdene | Gauteng | South Africa | 2092 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00326716
Other Study ID Numbers:
- AI424-182
First Posted:
May 17, 2006
Last Update Posted:
Nov 16, 2011
Last Verified:
Nov 1, 2011
Keywords provided by Bristol-Myers Squibb
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Pregnant participants were enrolled at 6 sites: United States (2), South Africa (3), and Puerto Rico (1). |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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 born to mothers receiving treatment with ATV 300 mg / RTV 100 mg during the third trimester of pregnancy. | Infants born to mothers receiving treatment with ATV 400 mg / RTV 100 mg during the third trimester of pregnancy. |
| Period Title: Pre-Natal Mothers | ||||
| STARTED | 20 | 21 | 0 | 0 |
| COMPLETED | 19 | 19 | 0 | 0 |
| NOT COMPLETED | 1 | 2 | 0 | 0 |
| Period Title: Pre-Natal Mothers | ||||
| STARTED | 0 | 0 | 20 | 20 |
| COMPLETED | 0 | 0 | 20 | 20 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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 of all reporting groups |
| Overall Participants | 20 | 21 | 41 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
20
100%
|
21
100%
|
41
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (Years) [Median (Full Range) ] | |||
| Median (Full Range) [Years] |
29
|
28
|
28
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
20
100%
|
21
100%
|
41
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
17
85%
|
19
90.5%
|
36
87.8%
|
| White |
3
15%
|
1
4.8%
|
4
9.8%
|
| More than one race |
0
0%
|
1
4.8%
|
1
2.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| North America |
6
30%
|
6
28.6%
|
12
29.3%
|
| Africa |
14
70%
|
15
71.4%
|
29
70.7%
|
| HIV RNA Distribution at Baseline (c/mL) [Number] | |||
| <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 (Weeks) [Median (Full Range) ] | |||
| Median (Full Range) [Weeks] |
38
|
38
|
38
|
Outcome Measures
| Title | Maternal HIV Ribonucleic Acid (RNA) Level on Day of Delivery |
|---|---|
| Description | The maternal HIV RNA level is assessed by the Roche Amplicor® Ultrasensitive Assay Version 1.5. |
| Time Frame | Day of Delivery ± 2 Days |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Mothers ATV 300 mg / RTV 100 mg | Mothers ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 19 | 20 |
| HIV RNA < 400 copies/mL |
19
95%
|
20
95.2%
|
| HIV RNA < 50 copies/mL |
19
95%
|
19
90.5%
|
| Title | Median Change From Baseline to Day of Delivery in Maternal HIV RNA Level |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 18 | 19 |
| Median (Inter-Quartile Range) [log10 c / mL] |
-1.8
|
-2.37
|
| Title | Mean HIV RNA Level at Baseline |
|---|---|
| Description | |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Mothers ATV 300 mg / RTV 100 mg Third Trimester | Mothers ATV 400 mg / RTV 100 mg Third Trimester |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 20 | 21 |
| Mean (Standard Error) [log10 cm / mL] |
3.520
(0.232)
|
4.020
(0.171)
|
| Title | Median Change From Baseline to Day of Delivery in Maternal Cluster of Differentiation 4 (CD4) Cell Count |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 17 | 20 |
| Median (Inter-Quartile Range) [cells / mm^3] |
89
|
174
|
| Title | Mean CD4 Cell Count at Baseline |
|---|---|
| Description | |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Mothers ATV 300 mg / RTV 100 mg Third Trimester | Mothers ATV 400 mg / RTV 100 mg Third Trimester |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 20 | 21 |
| Mean (Standard Error) [cells / mm^3] |
435.0
(39.2)
|
390.0
(25.0)
|
| Title | Infant HIV Status |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All infants. |
| Arm/Group Title | Infant ATV 300 mg / RTV 100 mg | Infant ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 20 | 20 |
| HIV Positive |
0
0%
|
0
0%
|
| HIV Negative |
20
100%
|
20
95.2%
|
| Title | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | All Treated Mothers | All Infants |
|---|---|---|
| Arm/Group Description | Data are pooled for mothers in the ATV 300 mg / RTV 100 mg and the ATV 400 mg / 100 mg groups. | Data are pooled for infants in the ATV 300 mg / RTV 100 mg and the ATV 400 mg / 100 mg groups. |
| Measure Participants | 41 | 40 |
| Death (n=41, n=40) |
0
0%
|
0
0%
|
| Serious Adverse Event (n=41, n=40) |
16
80%
|
14
66.7%
|
| Total AEs Leading to Discontinuation (n=41, n=40) |
2
10%
|
2
9.5%
|
| Anemia Leading to Discontinuation (n=41, n=40) |
1
5%
|
2
9.5%
|
| Transaminitis Discontinuation (n=41, n=40) |
1
5%
|
0
0%
|
| Prematurity Causing Discontinuation (n=41, n=40) |
NA
NaN
|
1
4.8%
|
| All AEs (n=41, n=40) |
40
200%
|
40
190.5%
|
| Anemia (n=41, n=40) |
6
30%
|
3
14.3%
|
| Diarrhea (n=41, n=40) |
4
20%
|
4
19%
|
| Nausea (n=41, n=40) |
6
30%
|
0
0%
|
| Vomiting (n=41, n=40) |
7
35%
|
5
23.8%
|
| Jaundice (n=41, n=40) |
10
50%
|
20
95.2%
|
| Hyperbilirubinemia (n=41, n=40) |
1
5%
|
1
4.8%
|
| Ocular Icterus (n=41, n=40) |
3
15%
|
0
0%
|
| Skin / subcutaneous tissue disorders (n=41, n=40) |
10
50%
|
20
95.2%
|
| Title | Number of Participants With Grade 2 to Grade 4 AEs and SAEs |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | All Treated Mothers | All Infants |
|---|---|---|
| Arm/Group Description | Data are pooled for mothers in the ATV 300 mg / RTV 100 mg and the ATV 400 mg / 100 mg groups. | Data are pooled for infants in the ATV 300 mg / RTV 100 mg and the ATV 400 mg / 100 mg groups. |
| Measure Participants | 41 | 40 |
| Grade 2 to Grade 4 (n=41, n=40) |
32
160%
|
19
90.5%
|
| Related Grade 2 to Grade 4 (n=41, n=40) |
10
50%
|
0
0%
|
| Grade 3 to Grade 4 (n=41, n=40) |
12
60%
|
8
38.1%
|
| Grade 3 to Grade 4 Total Bilirubin (n=41, n=40) |
19
95%
|
7
33.3%
|
| Title | SAEs in Enrolled Mothers |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were analyzed for all treated and untreated mothers. |
| Arm/Group Title | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 20 | 21 |
| Any Adverse Experience |
7
35%
|
8
38.1%
|
| Blood and Lymphatic System Disorders |
1
5%
|
2
9.5%
|
| Anemia |
1
5%
|
2
9.5%
|
| Cardiac Disorders |
1
5%
|
1
4.8%
|
| Cardiomyopathy |
1
5%
|
0
0%
|
| Sinus Arrhythmia |
0
0%
|
1
4.8%
|
| Gastrointestinal Disorders |
0
0%
|
1
4.8%
|
| Abdominal Hernia |
0
0%
|
1
4.8%
|
| Hepatobiliary Disorders |
0
0%
|
1
4.8%
|
| Hyperbilirubinemia |
0
0%
|
1
4.8%
|
| Infections and Infestations |
2
10%
|
2
9.5%
|
| Endometrial Decidual |
2
10%
|
0
0%
|
| Pneumonia |
0
0%
|
1
4.8%
|
| Sepsis |
0
0%
|
1
4.8%
|
| Investigations |
0
0%
|
1
4.8%
|
| Transaminases Increased |
0
0%
|
1
4.8%
|
| Pregnancy, Puerperium, and Perinatal Conditions |
2
10%
|
2
9.5%
|
| Amenorrhea |
0
0%
|
1
4.8%
|
| Pre-eclampsia |
1
5%
|
1
4.8%
|
| Pregnancy Induced Hypertension |
0
0%
|
0
0%
|
| Premature Rupture of Membranes |
1
5%
|
0
0%
|
| Vascular Disorders |
1
5%
|
1
4.8%
|
| Hypertension |
0
0%
|
1
4.8%
|
| Hemorrhage |
1
5%
|
0
0%
|
| Title | SAEs in Enrolled Infants |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| SAEs were recorded for all enrolled infants. |
| Arm/Group Title | Infant ATV 300 mg / RTV 100 mg | Infant ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | Infants of mothers taking ATV 300 mg / RTV 100 mg at birth. | Infants of mothers taking ATV 400 mg / RTV 100 mg at birth. |
| Measure Participants | 20 | 20 |
| Any Adverse Experience |
10
50%
|
4
19%
|
| Blood and Lymphatic System Disorders |
1
5%
|
1
4.8%
|
| Anemia |
1
5%
|
1
4.8%
|
| Cardiac Disorders |
1
5%
|
0
0%
|
| Cardio-Respiratory Arrest |
1
5%
|
0
0%
|
| Restrictive Cardiomyopathy |
1
5%
|
0
0%
|
| Congenital, Familial, and Genetic Disorders |
0
0%
|
1
4.8%
|
| Atrial Septal Defect |
0
0%
|
1
4.8%
|
| Gastrointestinal Disorders |
1
5%
|
0
0%
|
| Constipation |
1
5%
|
0
0%
|
| Vomiting |
1
5%
|
0
0%
|
| Hepatobiliary Disorders |
1
5%
|
1
4.8%
|
| Hyperbilirubinemia |
0
0%
|
1
4.8%
|
| Jaundice |
1
5%
|
0
0%
|
| Infections and Infestations |
4
20%
|
2
9.5%
|
| Bronchiolitis |
0
0%
|
2
9.5%
|
| Gastroenteritis |
1
5%
|
0
0%
|
| Meningitis |
1
5%
|
0
0%
|
| Pneumonia |
0
0%
|
1
4.8%
|
| Sepsis |
1
5%
|
0
0%
|
| Syphilis |
1
5%
|
0
0%
|
| Injury, Poisoning, and Procedural Complications |
1
5%
|
0
0%
|
| Overdose |
1
5%
|
0
0%
|
| Metabolism and Nutrition Disorders |
1
5%
|
1
4.8%
|
| Hyperkalemia |
1
5%
|
0
0%
|
| Hypoglycemia |
0
0%
|
1
4.8%
|
| Nervous System Disorders |
1
5%
|
0
0%
|
| Cerebral Ischemia |
1
5%
|
0
0%
|
| Convulsion |
1
5%
|
0
0%
|
| Pregnancy, Puerperium, and Perinatal Conditions |
1
5%
|
1
4.8%
|
| Premature Baby |
1
5%
|
1
4.8%
|
| Respiratory, Thoracic, and Mediastinal Disorders |
2
10%
|
0
0%
|
| Neonatal Respiratory Distress Syndrome |
1
5%
|
0
0%
|
| Respiratory Distress |
1
5%
|
0
0%
|
| Title | Infant Gestational Age at Delivery |
|---|---|
| Description | |
| Time Frame | At the time of delivery |
Outcome Measure Data
| Analysis Population Description |
|---|
| All infants. |
| Arm/Group Title | Mothers ATV 300 mg / 100 mg Third Trimester | Mothers ATV 400 mg / 100 mg Third Trimester |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 20 | 20 |
| Mean (Standard Error) [Weeks] |
38
(0.3)
|
38
(0.3)
|
| Title | Infant Gender |
|---|---|
| Description | |
| Time Frame | At the time of delivery |
Outcome Measure Data
| Analysis Population Description |
|---|
| All infants. |
| Arm/Group Title | Mothers ATV 300 mg / 100 mg Third Trimester | Mothers ATV 400 mg / 100 mg Third Trimester |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 20 | 20 |
| Male |
12
60%
|
9
42.9%
|
| Female |
8
40%
|
11
52.4%
|
| Title | Infant Race |
|---|---|
| Description | |
| Time Frame | At the time of delivery |
Outcome Measure Data
| Analysis Population Description |
|---|
| All infants. |
| Arm/Group Title | Mothers ATV 300 mg / 100 mg Third Trimester | Mothers ATV 400 mg / 100 mg Third Trimester |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 20 | 20 |
| Black |
15
75%
|
18
85.7%
|
| White |
5
25%
|
1
4.8%
|
| Mixed Race |
0
0%
|
1
4.8%
|
| Title | Mean ATV Maximum Plasma Concentration (Cmax) in One Dosing Interval |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the pharmacokinetic (PK) concentration data set. |
| Arm/Group Title | 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 |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [ng / mL] |
3,729.09
|
3,291.46
|
4,210.76
|
| Title | Mean RTV Maximum Plasma Concentration (Cmax) in One Dosing Interval |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set. |
| Arm/Group Title | 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 |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [ng / mL] |
530.81
|
587.36
|
524.48
|
| Title | Mean ATV Area Under the Concentration Curve (AUC TAU) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set. |
| Arm/Group Title | 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 |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [ng•h / mL] |
34,399.13
|
34,251.50
|
46,602.45
|
| Title | Mean RTV Area Under the Concentration Curve (AUC TAU) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set. |
| Arm/Group Title | 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 |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [ng•h / mL] |
4,500.03
|
4,664.93
|
4,383.30
|
| Title | Mean ATV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set. |
| Arm/Group Title | 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 |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [ng•h / mL] |
663.78
|
668.48
|
916.63
|
| Title | Mean RTV Trough Plasma Concentration (Cmin) 24 Hours Following the Daily Dose |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set. |
| Arm/Group Title | 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 |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [ng•h / mL] |
50.10
|
41.12
|
38.05
|
| Title | Mean ATV Terminal Elimination Half Life (T 1/2) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set. |
| Arm/Group Title | Mothers ATV 300 mg / 100 mg Second Trimester | Mothers ATV 300 mg / 100 mg Third Trimester | Mothers ATV 400 mg / 100 mg Third Trimester |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [Hours] |
10.42
|
12.10
|
12.17
|
| Title | Mean Atazanavir Maternal Plasma Concentration and Neonatal Cord Blood Concentration |
|---|---|
| Description | Mean atazanavir maternal plasma concentration and neonatal cord blood concentration as measured at the time of delivery. |
| Time Frame | At Time of Delivery |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Mothers ATV 300 mg / RTV 100 mg | Mothers ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 20 | 21 |
| Maternal Serum Concentration |
1,412.05
(888.85)
|
1,568.06
(846.44)
|
| Cord Blood Concentration |
273.20
(182.04)
|
231.49
(158.29)
|
| Title | Median Infant Total Bilirubin Level |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Infant ATV 300 mg / RTV 100 mg | Infant ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 20 | 20 |
| Day 1 (Birth) |
3.20
|
3.25
|
| Day 3 |
8.40
|
9.20
|
| Day 5 |
7.10
|
9.25
|
| Day 7 |
5.10
|
7.30
|
| Title | Mean Atazanavir Plasma Protein Binding |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 20 | 21 |
| 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)
|
| Title | Multicenter AIDS Cohort Study (MACS) Participant Adherence to Regimen and Drug Components for ATV 300 mg / RTV 100 mg Test Dose |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants were included in this evaluation. |
| Arm/Group Title | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 20 | 21 |
| Study Week 2 Regimen (n = 20,18) |
20
100%
|
17
81%
|
| Study Week 2 ATV (n = 20,18) |
20
100%
|
17
81%
|
| Study Week 2 RTV (n = 20,18) |
20
100%
|
17
81%
|
| Study Week 2 ZDV/3TC (n = 20,18) |
20
100%
|
17
81%
|
| Visit 1 Pregnancy Week 20 to 28 Regimen (n=12, 9) |
11
55%
|
8
38.1%
|
| Visit 1 Pregnancy Week 20 to 28 ATV (n=12, 9) |
12
60%
|
8
38.1%
|
| Visit 1 Pregnancy Week 20 to 28 RTV (n=12, 9) |
12
60%
|
9
42.9%
|
| Visit 1 Pregnancy Week 20 to 28 ZDV/3TC (n=12, 9) |
11
55%
|
9
42.9%
|
| Visit 2 Pregnancy Week 20 to 28 Regimen (n=8, 5) |
3
15%
|
3
14.3%
|
| Visit 2 Pregnancy Week 20 to 28 ATV (n=8, 5) |
8
40%
|
5
23.8%
|
| Visit 2 Pregnancy Week 20 to 28 RTV (n=8, 5) |
7
35%
|
4
19%
|
| Visit 2 Pregnancy Week 20 to 28 ZDV/3TC (n=8, 5) |
4
20%
|
4
19%
|
| Visit 3 Pregnancy Week 20 to 28 Regimen (n=6, 2) |
4
20%
|
2
9.5%
|
| Visit 3 Pregnancy Week 20 to 28 ATV (n=6, 2) |
5
25%
|
2
9.5%
|
| Visit 3 Pregnancy Week 20 to 28 RTV (n=6, 2) |
5
25%
|
2
9.5%
|
| Visit 3 Pregnancy Week 20 to 28 ADV/3TC (n=6, 2) |
4
20%
|
2
9.5%
|
| Visit 4 Pregnancy Wk 20 to 28 Regimen (n=0, 13) |
NA
NaN
|
13
61.9%
|
| Visit 4 Pregnancy Week 20 to 28 ATV (n=0, 13) |
NA
NaN
|
13
61.9%
|
| Visit 4 Pregnancy Week 20 to 28 RTV (n=0, 13) |
NA
NaN
|
13
61.9%
|
| Visit 4 Pregnancy Wk 20 to 28 ZDV/3TC (n=0, 13) |
NA
NaN
|
13
61.9%
|
| Visit 1 Pregnancy Wk 20 to Birth Regimen (n=20,20) |
19
95%
|
20
95.2%
|
| Visit 1 Pregnancy Week 20 to Birth ATV (n=20,20) |
20
100%
|
20
95.2%
|
| Visit 1 Pregnancy Week 20 to Birth RTV (n=20,20) |
20
100%
|
20
95.2%
|
| Visit 1 Pregnancy Wk 20 to Birth ZDV/3TC (n=20,20) |
19
95%
|
20
95.2%
|
| Visit 2 Pregnancy Wk 20 to Birth Regimen (n=19,19) |
18
90%
|
18
85.7%
|
| Visit 2 Pregnancy Week 20 to Birth ATV (n=19,19) |
19
95%
|
19
90.5%
|
| Visit 2 Pregnancy Week 20 to Birth RTV (n=19,19) |
19
95%
|
19
90.5%
|
| Visit 2 Pregnancy Wk 20 to Birth ZDV/3TC (n=19,19) |
18
90%
|
18
85.7%
|
| Visit 3 Pregnancy Wk 20 to Birth Regimen (n=15,19) |
12
60%
|
18
85.7%
|
| Visit 3 Pregnancy Week 20 to Birth ATV (n=15,19) |
13
65%
|
19
90.5%
|
| Visit 3 Pregnancy Week 20 to Birth RTV (n=15,19) |
13
65%
|
19
90.5%
|
| Visit 3 Pregnancy Wk 20 to Birth ZDV/3TC (n=15,19) |
12
60%
|
18
85.7%
|
| Visit 4 Pregnancy Wk 28 to Birth Regimen (n=5,15) |
5
25%
|
15
71.4%
|
| Visit 4 Pregnancy Week 28 to Birth ATV (n=5,15) |
5
25%
|
15
71.4%
|
| Visit 4 Pregnancy Week 28 to Birth RTV (n=5,15) |
5
25%
|
15
71.4%
|
| Visit 4 Pregnancy Wk 28 to Birth ZDV/3TC (n=5,15) |
5
25%
|
15
71.4%
|
| Visit 5 Pregnancy Wk 28 to Birth Regimen (n=1, 2) |
1
5%
|
2
9.5%
|
| Visit 5 Pregnancy Week 28 to Birth ATV (n=1, 2) |
1
5%
|
2
9.5%
|
| Visit 5 Pregnancy Week 28 to Birth RTV (n=1, 2) |
1
5%
|
2
9.5%
|
| Visit 5 Pregnancy Wk 28 to Birth ZDV/3TC (n=1, 2) |
1
5%
|
2
9.5%
|
| Visit 6 Pregnancy Wk 28 to Birth Regimen (n=0, 1) |
NA
NaN
|
1
4.8%
|
| Visit 6 Pregnancy Week 28 to Birth ATV (n=0, 1) |
NA
NaN
|
1
4.8%
|
| Visit 6 Pregnancy Week 28 to Birth RTV (n=0, 1) |
NA
NaN
|
1
4.8%
|
| Visit 6 Pregnancy Wk 28 to Birth ZDV/3TC (n=0, 1) |
NA
NaN
|
1
4.8%
|
| Postpartum Week 2 Regimen (n=19, 19) |
14
70%
|
18
85.7%
|
| Postpartum Week 2 ATV (n=18, 19) |
16
80%
|
18
85.7%
|
| Postpartum Week 2 RTV (n=18, 19) |
16
80%
|
18
85.7%
|
| Postpartum Week 2 ZDV/3TC (n =19, 19) |
14
70%
|
18
85.7%
|
| Postpartum Week 4 Regimen (n=17, 19) |
16
80%
|
18
85.7%
|
| Postpartum Week 4 ATV (n=17, 19) |
17
85%
|
19
90.5%
|
| Postpartum Week 4 RTV (n=17, 19) |
16
80%
|
19
90.5%
|
| Postpartum Week 4 ZDV/3TC (n=17, 19) |
17
85%
|
18
85.7%
|
| Title | Mean RTV Terminal Elimination Half Life (T 1/2) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set |
| Arm/Group Title | Mothers ATV 300 mg / 100 mg Second Trimester | Mothers ATV 300 mg / 100 mg Third Trimester | Mothers ATV 400 mg / 100 mg Third Trimester |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [Hours] |
5.03
|
5.28
|
5.10
|
| Title | Mean ATV Time of Maximum Observed Plasma Concentration (Tmax) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set. |
| Arm/Group Title | Mothers ATV 300 mg / 100 mg Second Trimester | Mothers ATV 300 mg / 100 mg Third Trimester | Mothers ATV 400 mg / 100 mg Third Trimester |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [Hours] |
3.68
|
2.94
|
3.30
|
| Title | Mean RTV Time of Maximum Observed Plasma Concentration (Tmax) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants in the PK concentration data set. |
| Arm/Group Title | Mothers ATV 300 mg / 100 mg Second Trimester | Mothers ATV 300 mg / 100 mg Third Trimester | Mothers ATV 400 mg / 100 mg Third Trimester |
|---|---|---|---|
| Arm/Group Description | 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 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 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. |
| Measure Participants | 9 | 20 | 20 |
| Geometric Mean (95% Confidence Interval) [Hours] |
6.11
|
4.15
|
4.63
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Infant ATV 300 mg / RTV 100 mg | Infant ATV 400 mg / RTV 100 mg | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg | ||||
| Arm/Group Description | Infants of mothers taking ATV 300 mg / RTV 100 mg at birth. | Infants of mothers taking ATV 400 mg / RTV 100 mg at birth. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| Infant ATV 300 mg / RTV 100 mg | Infant ATV 400 mg / RTV 100 mg | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Infant ATV 300 mg / RTV 100 mg | Infant ATV 400 mg / RTV 100 mg | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/20 (50%) | 4/20 (20%) | 7/20 (35%) | 8/21 (38.1%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 1/20 (5%) | 1/20 (5%) | 1/20 (5%) | 2/21 (9.5%) | ||||
| Cardiac disorders | ||||||||
| CARDIOMYOPATHY | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| SINUS ARRHYTHMIA | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| CARDIO-RESPIRATORY ARREST | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| RESTRICTIVE CARDIOMYOPATHY | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| Congenital, familial and genetic disorders | ||||||||
| ATRIAL SEPTAL DEFECT | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| VOMITING | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| CONSTIPATION | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| ABDOMINAL HERNIA | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| Hepatobiliary disorders | ||||||||
| JAUNDICE | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| HYPERBILIRUBINAEMIA | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| Infections and infestations | ||||||||
| SEPSIS | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| SYPHILIS | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| PNEUMONIA | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| MENINGITIS | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| BRONCHIOLITIS | 0/20 (0%) | 2/20 (10%) | 0/20 (0%) | 0/21 (0%) | ||||
| GASTROENTERITIS | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| ENDOMETRITIS DECIDUAL | 0/20 (0%) | 0/20 (0%) | 2/20 (10%) | 0/21 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| OVERDOSE | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| Investigations | ||||||||
| TRANSAMINASES INCREASED | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| Metabolism and nutrition disorders | ||||||||
| HYPERKALAEMIA | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| HYPOGLYCAEMIA | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| Nervous system disorders | ||||||||
| CONVULSION | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| CEREBRAL ISCHAEMIA | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| Pregnancy, puerperium and perinatal conditions | ||||||||
| AMNIORRHOEA | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| PRE-ECLAMPSIA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| PREMATURE BABY | 1/20 (5%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| PREMATURE RUPTURE OF MEMBRANES | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| RESPIRATORY DISTRESS | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| NEONATAL RESPIRATORY DISTRESS SYNDROME | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| Vascular disorders | ||||||||
| HAEMORRHAGE | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| HYPERTENSION | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 1/21 (4.8%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Infant ATV 300 mg / RTV 100 mg | Infant ATV 400 mg / RTV 100 mg | Mother ATV 300 mg / RTV 100 mg | Mother ATV 400 mg / RTV 100 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | 20/20 (100%) | 20/20 (100%) | 20/21 (95.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 1/20 (5%) | 1/20 (5%) | 2/20 (10%) | 4/21 (19%) | ||||
| LYMPHADENOPATHY | 1/20 (5%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| Congenital, familial and genetic disorders | ||||||||
| HYDROCELE | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| CONGENITAL NAEVUS | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| ATRIAL SEPTAL DEFECT | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| Eye disorders | ||||||||
| CONJUNCTIVITIS | 3/20 (15%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| OCULAR ICTERUS | 0/20 (0%) | 0/20 (0%) | 2/20 (10%) | 1/21 (4.8%) | ||||
| CONJUNCTIVAL HAEMORRHAGE | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| NAUSEA | 0/20 (0%) | 0/20 (0%) | 4/20 (20%) | 2/21 (9.5%) | ||||
| VOMITING | 1/20 (5%) | 3/20 (15%) | 5/20 (25%) | 2/21 (9.5%) | ||||
| DIARRHOEA | 1/20 (5%) | 3/20 (15%) | 3/20 (15%) | 1/21 (4.8%) | ||||
| DYSPEPSIA | 0/20 (0%) | 0/20 (0%) | 3/20 (15%) | 2/21 (9.5%) | ||||
| TOOTHACHE | 0/20 (0%) | 0/20 (0%) | 3/20 (15%) | 1/21 (4.8%) | ||||
| CONSTIPATION | 1/20 (5%) | 3/20 (15%) | 2/20 (10%) | 1/21 (4.8%) | ||||
| ABDOMINAL PAIN | 1/20 (5%) | 2/20 (10%) | 2/20 (10%) | 1/21 (4.8%) | ||||
| ABDOMINAL HERNIA | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| MOUTH ULCERATION | 1/20 (5%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| UMBILICAL HERNIA | 2/20 (10%) | 3/20 (15%) | 0/20 (0%) | 0/21 (0%) | ||||
| TONGUE GEOGRAPHIC | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| RECTAL HAEMORRHAGE | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| ABDOMINAL DISTENSION | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| ABDOMINAL PAIN LOWER | 0/20 (0%) | 0/20 (0%) | 2/20 (10%) | 0/21 (0%) | ||||
| PAROTID GLAND ENLARGEMENT | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| GASTROOESOPHAGEAL REFLUX DISEASE | 1/20 (5%) | 4/20 (20%) | 1/20 (5%) | 0/21 (0%) | ||||
| General disorders | ||||||||
| MASS | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| PAIN | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| FATIGUE | 0/20 (0%) | 0/20 (0%) | 4/20 (20%) | 0/21 (0%) | ||||
| PYREXIA | 1/20 (5%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| OEDEMA PERIPHERAL | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 2/21 (9.5%) | ||||
| Hepatobiliary disorders | ||||||||
| JAUNDICE | 9/20 (45%) | 10/20 (50%) | 4/20 (20%) | 6/21 (28.6%) | ||||
| HEPATOMEGALY | 0/20 (0%) | 2/20 (10%) | 0/20 (0%) | 0/21 (0%) | ||||
| Infections and infestations | ||||||||
| IMPETIGO | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| MASTITIS | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| RHINITIS | 0/20 (0%) | 3/20 (15%) | 0/20 (0%) | 2/21 (9.5%) | ||||
| INFLUENZA | 0/20 (0%) | 1/20 (5%) | 1/20 (5%) | 2/21 (9.5%) | ||||
| SINUSITIS | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| BODY TINEA | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| BRONCHITIS | 2/20 (10%) | 0/20 (0%) | 0/20 (0%) | 3/21 (14.3%) | ||||
| TRACHEITIS | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| CANDIDIASIS | 1/20 (5%) | 2/20 (10%) | 0/20 (0%) | 0/21 (0%) | ||||
| ORAL HERPES | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| PHARYNGITIS | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| TONSILLITIS | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 2/21 (9.5%) | ||||
| ENDOMETRITIS | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| OTITIS MEDIA | 3/20 (15%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| SKIN CANDIDA | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| WOUND SEPSIS | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| BRONCHIOLITIS | 2/20 (10%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| HERPES ZOSTER | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| GASTROENTERITIS | 1/20 (5%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| NASOPHARYNGITIS | 0/20 (0%) | 1/20 (5%) | 2/20 (10%) | 1/21 (4.8%) | ||||
| VIRAL INFECTION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| WOUND INFECTION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| ORAL CANDIDIASIS | 3/20 (15%) | 3/20 (15%) | 2/20 (10%) | 0/21 (0%) | ||||
| VAGINAL INFECTION | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 2/21 (9.5%) | ||||
| VAGINITIS BACTERIAL | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| FUNGAL SKIN INFECTION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| URINARY TRACT INFECTION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 6/21 (28.6%) | ||||
| SKIN BACTERIAL INFECTION | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| VULVOVAGINAL CANDIDIASIS | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| LOWER RESPIRATORY TRACT INFECTION | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| UPPER RESPIRATORY TRACT INFECTION | 4/20 (20%) | 10/20 (50%) | 8/20 (40%) | 4/21 (19%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| OVERDOSE | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| ARTHROPOD BITE | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| PROCEDURAL PAIN | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| SKIN LACERATION | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| VACCINATION COMPLICATION | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| Investigations | ||||||||
| CARDIAC MURMUR | 0/20 (0%) | 2/20 (10%) | 0/20 (0%) | 0/21 (0%) | ||||
| WEIGHT DECREASED | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| HAEMOGLOBIN DECREASED | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| CULTURE URINE POSITIVE | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| WHITE BLOOD CELLS URINE POSITIVE | 0/20 (0%) | 0/20 (0%) | 2/20 (10%) | 0/21 (0%) | ||||
| ELECTROCARDIOGRAM T WAVE INVERSION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| ANOREXIA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| HYPOGLYCAEMIA | 1/20 (5%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| DECREASED APPETITE | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| GESTATIONAL DIABETES | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| BURSITIS | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| BACK PAIN | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| ARTHRALGIA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| JOINT STIFFNESS | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| JOINT HYPEREXTENSION | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| Nervous system disorders | ||||||||
| SYNCOPE | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| HEADACHE | 0/20 (0%) | 0/20 (0%) | 7/20 (35%) | 2/21 (9.5%) | ||||
| SCIATICA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| DIZZINESS | 0/20 (0%) | 0/20 (0%) | 3/20 (15%) | 1/21 (4.8%) | ||||
| POST HERPETIC NEURALGIA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| Pregnancy, puerperium and perinatal conditions | ||||||||
| PREMATURE LABOUR | 0/20 (0%) | 0/20 (0%) | 3/20 (15%) | 1/21 (4.8%) | ||||
| PROLONGED LABOUR | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| CAPUT SUCCEDANEUM | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| JAUNDICE NEONATAL | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| NEONATAL DISORDER | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| FOETAL DISTRESS SYNDROME | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| PREGNANCY INDUCED HYPERTENSION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| PREMATURE RUPTURE OF MEMBRANES | 0/20 (0%) | 0/20 (0%) | 4/20 (20%) | 1/21 (4.8%) | ||||
| Psychiatric disorders | ||||||||
| DEPRESSION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| Renal and urinary disorders | ||||||||
| DYSURIA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| PROTEINURIA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| PELVIC PAIN | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| VAGINAL DISCHARGE | 0/20 (0%) | 0/20 (0%) | 2/20 (10%) | 2/21 (9.5%) | ||||
| VAGINAL HAEMORRHAGE | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 2/21 (9.5%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| COUGH | 5/20 (25%) | 0/20 (0%) | 4/20 (20%) | 3/21 (14.3%) | ||||
| DYSPNOEA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| SNEEZING | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| EPISTAXIS | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| TACHYPNOEA | 0/20 (0%) | 3/20 (15%) | 0/20 (0%) | 0/21 (0%) | ||||
| RHINORRHOEA | 1/20 (5%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| NASAL CONGESTION | 7/20 (35%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
| SINUS CONGESTION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| NOCTURNAL DYSPNOEA | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| OROPHARYNGEAL PAIN | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| RESPIRATORY DISTRESS | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| RASH | 3/20 (15%) | 4/20 (20%) | 1/20 (5%) | 3/21 (14.3%) | ||||
| ECZEMA | 2/20 (10%) | 3/20 (15%) | 1/20 (5%) | 1/21 (4.8%) | ||||
| DRY SKIN | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| PRURITUS | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 3/21 (14.3%) | ||||
| HEAT RASH | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| PETECHIAE | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| DERMATITIS | 2/20 (10%) | 2/20 (10%) | 0/20 (0%) | 0/21 (0%) | ||||
| SEBORRHOEA | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| RASH MACULAR | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| RASH GENERALISED | 1/20 (5%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
| DERMATITIS DIAPER | 0/20 (0%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| NAIL PIGMENTATION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| DERMATITIS ALLERGIC | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| NAIL DISCOLOURATION | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) | 0/21 (0%) | ||||
| SEBORRHOEIC DERMATITIS | 1/20 (5%) | 1/20 (5%) | 0/20 (0%) | 0/21 (0%) | ||||
| Vascular disorders | ||||||||
| HYPERTENSION | 0/20 (0%) | 0/20 (0%) | 3/20 (15%) | 3/21 (14.3%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | BMS Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| clinical.trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00326716
Other Study ID Numbers:
- AI424-182
First Posted:
May 17, 2006
Last Update Posted:
Nov 16, 2011
Last Verified:
Nov 1, 2011