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Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Resource-Limited Countries (PROMISE)

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ClinicalTrials.gov Identifier: NCT01061151
Recruitment Status : Completed
First Posted : February 2, 2010
Results First Posted : February 9, 2018
Last Update Posted : February 9, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition HIV Infections
Interventions Drug: Zidovudine (ZDV)
Drug: Nevirapine (NVP): Antepartum Mothers
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail
Drug: Lamivudine-Zidovudine (3TC-ZDV)
Drug: Lopinavir-ritonavir (LPV-RTV)
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])
Drug: Nevirapine (NVP): Infant short-course
Drug: Nevirapine (NVP): Infant extended
Other: No Intervention
Other: Discontinue triple ARVs
Other: Continue triple ARVs
Enrollment 3747
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Antepartum Arm A Antepartum Arm B Antepartum Arm C Late Presenters
Hide Arm/Group Description Mothers received ZDV+sdNVP+TRV tail Mothers received Triple ARV (3TC-ZDV/LPV-RTV) Mothers received Triple ARV (FTC-TDF/LPV-RTV) Registrational component to assess entry criteria for possible randomization in the Postpartum Component
Period Title: Protocol Version 2.0: 04/2011-09/2012
Started 855 861 25 129
Mothers That Met All Inclusion Criteria 853 861 24 129
Completed 623 620 16 101
Not Completed 232 241 9 28
Reason Not Completed
Protocol Violation             2             0             0             1
Death             6             9             1             2
Withdrawal by Subject             89             82             2             10
Lost to Follow-up             73             65             2             10
Site Closure             15             19             1             0
Subject Unable to Get to Clinic             44             61             2             5
Other Reason             3             5             1             0
Period Title: Protocol Version 3.0: 10/2012-10/2014
Started 694 686 422 75
Mothers That Met All Inclusion Criteria 694 684 421 75
Completed 542 548 345 55
Not Completed 152 138 77 20
Reason Not Completed
Protocol Violation             0             0             2             4
Adverse Event             1             0             0             0
Death             3             5             1             1
Withdrawal by Subject             54             52             31             3
Lost to Follow-up             49             36             25             4
Site Closure             12             11             2             0
Subject Unable to Get to Clinic             28             26             15             5
Other Reason             5             8             1             3
Arm/Group Title Antepartum Arm A Antepartum Arm B Antepartum Arm C Late Presenters Total
Hide Arm/Group Description Mothers received ZDV+sdNVP+TRV tail Mothers received Triple ARV (3TC-ZDV/LPV-RTV) Mothers received Triple ARV (FTC-TDF/LPV-RTV) Registrational component to assess entry criteria for possible randomization in the Postpartum Component Total of all reporting groups
Overall Number of Baseline Participants 1547 1545 445 204 3741
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
26.5
(22.8 to 30.1)
26.6
(23.3 to 30.3)
26.4
(22.7 to 30.4)
26.8
(23.2 to 31.1)
26.5
(23.0 to 30.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
Female
1547
 100.0%
1545
 100.0%
445
 100.0%
204
 100.0%
3741
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Black Non-Hispanic Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
1493
  96.5%
1487
  96.2%
440
  98.9%
183
  89.7%
3603
  96.3%
Hispanic (Regardless of Race) Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
7
   0.5%
12
   0.8%
4
   0.9%
2
   1.0%
25
   0.7%
Asian, Pacific Islander Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
47
   3.0%
46
   3.0%
1
   0.2%
19
   9.3%
113
   3.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Malawi Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
489
  31.6%
493
  31.9%
155
  34.8%
31
  15.2%
1168
  31.2%
Tanzania Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
23
   1.5%
24
   1.6%
10
   2.2%
0
   0.0%
57
   1.5%
South Africa Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
513
  33.2%
510
  33.0%
78
  17.5%
27
  13.2%
1128
  30.2%
Uganda Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
207
  13.4%
205
  13.3%
85
  19.1%
9
   4.4%
506
  13.5%
Zimbabwe Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
237
  15.3%
236
  15.3%
99
  22.2%
116
  56.9%
688
  18.4%
Zambia Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
32
   2.1%
31
   2.0%
18
   4.0%
2
   1.0%
83
   2.2%
India Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
46
   3.0%
46
   3.0%
0
   0.0%
19
   9.3%
111
   3.0%
Weight   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Kg
Number Analyzed 1547 participants 1545 participants 445 participants 200 participants 3737 participants
64
(57.5 to 73.5)
64.6
(58 to 74.1)
64.4
(58 to 75.9)
60.9
(53 to 68.9)
64
(57.5 to 74)
[1]
Measure Analysis Population Description: Some late presenters had incomplete measurements
BMI   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Kg/m^2
Number Analyzed 1545 participants 1535 participants 442 participants 198 participants 3720 participants
25.9
(23.5 to 29.5)
26.3
(23.4 to 29.8)
26.3
(23.5 to 30.1)
23.6
(21.8 to 26.8)
26
(23.4 to 29.6)
[1]
Measure Analysis Population Description: Some participants had incomplete measurements for either weight, height, or both.
HIV RNA level prior to randomization   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Copies/ml
Number Analyzed 1540 participants 1542 participants 445 participants 196 participants 3723 participants
6409
(1450.5 to 22720)
8002
(1854 to 28767)
8393
(1909 to 28454)
12140
(2407.5 to 39138.5)
7409
(1708 to 26350)
[1]
Measure Analysis Population Description: Baseline HIV RNA data was incomplete for some participants.
Viral Load at enrollment   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 1540 participants 1542 participants 445 participants 196 participants 3723 participants
3.8
(3.2 to 4.4)
3.9
(3.3 to 4.5)
3.9
(3.3 to 4.5)
4.1
(3.4 to 4.6)
3.9
(3.2 to 4.4)
[1]
Measure Analysis Population Description: Baseline HIV RNA data was incomplete for some participants.
CD4 count at screening  
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^3
Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
534
(435 to 678)
526
(439 to 651)
538
(434 to 684)
520
(353 to 723)
530
(434 to 670)
ALT (SGPT)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units/liter
Number Analyzed 1547 participants 1545 participants 445 participants 196 participants 3733 participants
12
(10 to 16)
12
(9 to 15)
12
(9 to 15)
16.5
(12 to 22)
12
(10 to 16)
[1]
Measure Analysis Population Description: Baseline Alanine Aminotransferase (ALT) values were incomplete for some late presenters.
Hemoglobin  
Median (Inter-Quartile Range)
Unit of measure:  G/dl
Number Analyzed 1547 participants 1545 participants 445 participants 204 participants 3741 participants
11
(10.2 to 11.8)
11.1
(10.3 to 11.8)
11
(10.3 to 11.8)
10.6
(9.5 to 11.7)
11
(10.2 to 11.8)
WBC   [1] 
Median (Inter-Quartile Range)
Unit of measure:  (cells/mm^3)
Number Analyzed 1547 participants 1545 participants 445 participants 196 participants 3733 participants
6800
(5670 to 8200)
6900
(5700 to 8200)
6840
(5700 to 7900)
8660
(6895 to 10755)
6900
(5700 to 8250)
[1]
Measure Analysis Population Description: Baseline White Blood Cell (WBC) values were incomplete for some participants.
Absolute Neutrophil Count at Baseline   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^3
Number Analyzed 1547 participants 1545 participants 445 participants 196 participants 3733 participants
4140
(3250 to 5360)
4209
(3297 to 5300)
3990
(3220 to 4990)
5680
(4342.5 to 7662.5)
4220
(3297 to 5400)
[1]
Measure Analysis Population Description: Baseline Absolute Neutrophil Count (ANC) values were incomplete for some participants.
Platelet count   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^3
Number Analyzed 1547 participants 1544 participants 444 participants 195 participants 3730 participants
238000
(200000 to 282000)
236000
(196000 to 282000)
242500
(203000 to 290000)
255000
(217000 to 321000)
239000
(200000 to 285000)
[1]
Measure Analysis Population Description: Baseline platelet counts were incomplete for some participants.
Serum Creatinine   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mg/dL
Number Analyzed 1547 participants 1545 participants 445 participants 199 participants 3736 participants
0.5
(0.4 to 0.6)
0.5
(0.4 to 0.6)
0.5
(0.4 to 0.6)
0.6
(0.5 to 0.6)
0.5
(0.4 to 0.6)
[1]
Measure Analysis Population Description: Baseline Serum Creatinine values were incomplete for some participants.
WHO Clinical Staging of HIV/AIDS   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1544 participants 1542 participants 445 participants 169 participants 3700 participants
Clinical stage I
1493
  96.7%
1506
  97.7%
434
  97.5%
165
  97.6%
3598
  97.2%
Clinical stage II
50
   3.2%
34
   2.2%
11
   2.5%
4
   2.4%
99
   2.7%
Clinical stage III
1
   0.1%
2
   0.1%
0
   0.0%
0
   0.0%
3
   0.1%
[1]
Measure Description: Clinical staging of HIV/AIDS by WHO definitions (WHO, 2007). Staging is based on clinical findings that guide the diagnosis, evaluation, and management of HIV/AIDS. Clinical stages are categorized as 1 through 4, progressing from primary HIV infection to advanced HIV/AIDS. These stages are defined by specific clinical conditions or symptoms as described in the reference.
[2]
Measure Analysis Population Description: Baseline WHO staging category was incomplete for some participants.
Calculated Creatinine Clearance (ml/min)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1547 participants 1545 participants 445 participants 199 participants 3736 participants
<= 50 ml/min
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.5%
1
   0.0%
> 50 - 60 ml/min
1
   0.1%
0
   0.0%
1
   0.2%
1
   0.5%
3
   0.1%
> 60 - 80 ml/min
5
   0.3%
5
   0.3%
2
   0.4%
2
   1.0%
14
   0.4%
> 80 - 100 ml/min
27
   1.7%
31
   2.0%
6
   1.3%
10
   5.0%
74
   2.0%
> 100 - 120 ml/min
90
   5.8%
108
   7.0%
39
   8.8%
31
  15.6%
268
   7.2%
> 120 ml/min
1424
  92.0%
1401
  90.7%
397
  89.2%
154
  77.4%
3376
  90.4%
[1]
Measure Analysis Population Description: Baseline Calculated Creatinine Clearance values were incomplete for some participants
Gestational age at study entry (weeks)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Weeks
Number Analyzed 1547 participants 1544 participants 445 participants 194 participants 3730 participants
25.7
(20.9 to 30.3)
25.2
(20.6 to 30.1)
26
(21.9 to 31.1)
38.6
(37.3 to 40)
25.6
(21.1 to 30.4)
[1]
Measure Analysis Population Description: Baseline gestational age was incomplete for some participants.
Gestational age at study entry   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1547 participants 1544 participants 445 participants 10 participants 3546 participants
<14 weeks
10
   0.6%
8
   0.5%
2
   0.4%
0
   0.0%
20
   0.6%
14 - <28 weeks
956
  61.8%
1008
  65.3%
264
  59.3%
0
   0.0%
2228
  62.8%
28 - <34 weeks
418
  27.0%
368
  23.8%
116
  26.1%
1
  10.0%
903
  25.5%
34 - < 37 weeks
117
   7.6%
113
   7.3%
45
  10.1%
0
   0.0%
275
   7.8%
>= 37 weeks
46
   3.0%
47
   3.0%
18
   4.0%
9
  90.0%
120
   3.4%
[1]
Measure Analysis Population Description: Baseline gestational age was incomplete for some participants.
The Most Complex ARV Regimen for Prior PMTCT   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1539 participants 1544 participants 445 participants 204 participants 3732 participants
HAART including NNRTI
7
   0.5%
5
   0.3%
2
   0.4%
0
   0.0%
14
   0.4%
sdNVP+ZDV
33
   2.1%
48
   3.1%
6
   1.3%
0
   0.0%
87
   2.3%
sdNVP
41
   2.7%
46
   3.0%
15
   3.4%
2
   1.0%
104
   2.8%
One PI
0
   0.0%
1
   0.1%
0
   0.0%
0
   0.0%
1
   0.0%
One NRTI
2
   0.1%
2
   0.1%
0
   0.0%
0
   0.0%
4
   0.1%
No ARVs for prior PMTCT/no prior pregnancy
1456
  94.6%
1442
  93.4%
422
  94.8%
202
  99.0%
3522
  94.4%
[1]
Measure Analysis Population Description:

Baseline ARV history data were incomplete for some participants.

PI - Protease Inhibitor, NNRTI - Non Nucleoside Reverse Transcriptase Inhibitor, ZDV - Zidovudine, NVP - Nevirapine, NRTI - Nucleoside Reverse Transcriptase Inhibitor

The Last ARV Regimen before Entry during the Current Pregnancy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1539 participants 1544 participants 445 participants 204 participants 3732 participants
HAART including NNRTI
1
   0.1%
1
   0.1%
0
   0.0%
7
   3.4%
9
   0.2%
Two NRTIs
2
   0.1%
5
   0.3%
3
   0.7%
10
   4.9%
20
   0.5%
sdNVP+ZDV
2
   0.1%
0
   0.0%
0
   0.0%
1
   0.5%
3
   0.1%
sdNVP
5
   0.3%
2
   0.1%
0
   0.0%
33
  16.2%
40
   1.1%
One NRTI
326
  21.2%
336
  21.8%
125
  28.1%
0
   0.0%
787
  21.1%
No ARVs during the current pregnancy
1203
  78.2%
1200
  77.7%
317
  71.2%
153
  75.0%
2873
  77.0%
[1]
Measure Analysis Population Description:

Baseline ARV history data were incomplete for some participants.

NNRTI - Non Nucleoside Reverse Transcriptase Inhibitor, NRTI - Nucleoside Reverse Transcriptase Inhibitor, NVP - Nevirapine, ZDV - Zidovudine

1.Primary Outcome
Title Antepartum Component: Number of Confirmed Infant HIV Infections
Hide Description Defined as HIV nucleic acid test (NAT) positivity of the specimen drawn at either the birth (Day 0-5) or Week 1 (Day 6-14) visit, confirmed by HIV NAT positivity of a second specimen collected at a different time point
Time Frame Measured at birth or Week 1 study visit
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis includes data from periods 1 and 2. Analysis is among the live births with HIV test results summarized for the maternal-infant set (the worst outcome summarized for cases of multiple births). Analysis used the principle of intent to treat.
Arm/Group Title Antepartum Arm A Antepartum Arm B Antepartum Arm C
Hide Arm/Group Description:
Mothers Received ZDV+sdNVP+TRV Tail
Mothers received Triple ARV (3TC-ZDV/LPV-RTV)
Mothers Received Triple ARV (FTC-TDF/LPV-RTV)
Overall Number of Participants Analyzed 1386 1385 325
Measure Type: Count of Participants
Unit of Measure: Participants
25
   1.8%
7
   0.5%
2
   0.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antepartum Arm A, Antepartum Arm B, Antepartum Arm C
Comments Arm B and Arm C were combined and compared to Arm A. This comparison was an a priori planned comparison.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.3
Confidence Interval (2-Sided) 96.5%
-2.1 to -0.4
Estimation Comments The combination of Arm B and Arm C minus Arm A, based on a repeated confidence interval (Lan–DeMets approach with an O’Brien–Fleming type I error spending function to preserve an experiment-wise type I error rate of 5%).
2.Primary Outcome
Title Antepartum Component: Number of Mothers With Grade 3 or Higher Toxicities and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events
Hide Description These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).
Time Frame Measured through the Week 1 postpartum study visit
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Mothers with no safety data available after baseline were not included. Analysis used the principle of intent to treat.
Arm/Group Title Antepartum Arm A Antepartum Arm B Antepartum Arm C
Hide Arm/Group Description:
Mothers received ZDV+sdNVP+TRV Tail
Mothers received Triple ARV (3TC-ZDV/LPV-RTV)
Mothers received Triple ARV (FTC-TDF/LPV-RTV)
Overall Number of Participants Analyzed 1521 1520 424
Measure Type: Count of Participants
Unit of Measure: Participants
Periods 1 and 2 Number Analyzed 1510 participants 1505 participants 0 participants
261
  17.3%
318
  21.1%
Period 2 Number Analyzed 393 participants 385 participants 380 participants
59
  15.0%
61
  15.8%
60
  15.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antepartum Arm A, Antepartum Arm B
Comments Periods 1 and 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Antepartum Arm A, Antepartum Arm C
Comments Period 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.77
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Antepartum Arm B, Antepartum Arm C
Comments Period 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.99
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Primary Outcome
Title Antepartum Component: Number of Mothers With Obstetrical Complications
Hide Description [Not Specified]
Time Frame Measured through the Week 1 postpartum study visit
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Mothers who do not have any obstetrical complications information available after study entry are not included. Analysis used the principle of intent to treat.
Arm/Group Title Antepartum Arm A Antepartum Arm B Antepartum Arm C
Hide Arm/Group Description:
Mothers received ZDV+sdNVP+TRV Tail
Mothers received Triple ARV (3TC-ZDV/LPV-RTV)
Mothers received Triple ARV (FTC-TDF/LPV-RTV)
Overall Number of Participants Analyzed 1521 1520 424
Measure Type: Count of Participants
Unit of Measure: Participants
Periods 1 and 2 Number Analyzed 1521 participants 1510 participants 0 participants
89
   5.9%
75
   5.0%
Period 2 Number Analyzed 401 participants 398 participants 391 participants
20
   5.0%
12
   3.0%
23
   5.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antepartum Arm A, Antepartum Arm B
Comments Periods 1 and 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Antepartum Arm A, Antepartum Arm C
Comments Period 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Antepartum Arm B, Antepartum Arm C
Comments Period 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.06
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Primary Outcome
Title Antepartum Component: Number of Mothers With Adverse Pregnancy Outcomes (e.g.,Stillbirth, Preterm Delivery (< 37 Weeks), Low Birth Weight (< 2,500 Grams), and Congenital Anomalies)
Hide Description Composite outcome
Time Frame Measured at birth
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes mothers with confirmed infant birth outcome as live birth, stillbirth, or spontaneous abortion and outcome assessments. Multiple gestation pregnancies (twins and triplets) were summarized at the unique mother level. Analysis used the principle of intent to treat.
Arm/Group Title Antepartum Arm A Antepartum Arm B Antepartum Arm C
Hide Arm/Group Description:
Mothers received ZDV+sdNVP+TRV Tail
Mothers received Triple ARV (3TC-ZDV/LPV-RTV)
Mothers received Triple ARV (FTC-TDF/LPV-RTV)
Overall Number of Participants Analyzed 1451 1447 372
Measure Type: Count of Participants
Unit of Measure: Participants
Periods 1 and 2 Number Analyzed 1451 participants 1447 participants 0 participants
389
  26.8%
563
  38.9%
Period 2 Number Analyzed 349 participants 348 participants 341 participants
91
  26.1%
123
  35.3%
111
  32.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antepartum Arm A, Antepartum Arm B
Comments Periods 1 and 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Antepartum Arm A, Antepartum Arm C
Comments Period 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Antepartum Arm B, Antepartum Arm C
Comments Period 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Primary Outcome
Title Postpartum Component: Incidence of Confirmed Infant HIV Infection
Hide Description Defined as infant HIV NAT positivity of a specimen drawn at any post-randomization visit (i.e., any visit after the Week 1 [Day 6-14] visit), confirmed by HIV NAT positivity of a second specimen drawn at a different time point. Analyses were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event.
Time Frame Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Mother-Infant (M-I) pairs, except 1 M-I pair where infant was infected at date of randomization, were included in the analyses. 35 M-I pairs with no post-randomization HIV test results were included and censored at the date of randomization in the analyses. Analyses were intent to treat.
Arm/Group Title Postpartum Arm A (Maternal Prophylaxis) Postpartum Arm B (Infant Prophylaxis)
Hide Arm/Group Description:
Mothers received prophylaxis [preferred regimen: TRV + LPV-RTV]. Infants received short-course NVP.
Infants received extended NVP.
Overall Number of Participants Analyzed 1219 1211
Measure Type: Number
Unit of Measure: New cases per 100 person-years
0.56 0.55
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Postpartum Arm A (Maternal Prophylaxis), Postpartum Arm B (Infant Prophylaxis)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.0
Confidence Interval (2-Sided) 96%
0.3 to 3.1
Estimation Comments The confidence interval was based on a repeated confidence interval.
6.Primary Outcome
Title Postpartum Component: Incidence of Grade 3 or Higher Adverse Events and Selected Grade 2 Hematologic, Renal, and Hepatic Adverse Events
Hide Description These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).
Time Frame Measured through site recommended duration of breastfeeding, complete cessation of breastfeeding or 18 months of age, whichever comes first
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All mothers were included in the analyses. 15 mothers with no post-randomization data were included and censored at the date of randomization in the analyses. Analyses were intent to treat.
Arm/Group Title Postpartum Arm A (Maternal Prophylaxis) Postpartum Arm B (Infant Prophylaxis)
Hide Arm/Group Description:
Mothers received prophylaxis [preferred regimen: TRV + LPV-RTV]. Infants received short-course NVP.
Infants received extended NVP.
Overall Number of Participants Analyzed 1220 1211
Measure Type: Number
Unit of Measure: New cases per 100 person-years
14.4 14.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Postpartum Arm A (Maternal Prophylaxis), Postpartum Arm B (Infant Prophylaxis)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
7.Primary Outcome
Title Maternal Health Component: Incidence of Progression to AIDS-defining Illness or Death
Hide Description AIDS-defining illness refers to the WHO Clinical Stage 4 illnesses in Appendix IV of the protocol. These events were reviewed and confirmed by an Endpoint review group.
Time Frame From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
Arm/Group Title Maternal Health Arm A (Continue Triple ARVs) Maternal Health Arm B (Discontinue Triple ARVs)
Hide Arm/Group Description:
Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Mothers discontinued triple ARV regimen.
Overall Number of Participants Analyzed 797 805
Measure Type: Number
Unit of Measure: New cases per 100 person-years
0.24 0.49
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maternal Health Arm A (Continue Triple ARVs), Maternal Health Arm B (Discontinue Triple ARVs)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.14 to 2.08
Estimation Comments The hazard ratio compares Arm A relative to Arm B.
8.Secondary Outcome
Title Antepartum Component: Number of Infant HIV Infections
Hide Description Detected by HIV NAT positivity
Time Frame Measured at the birth (<= 3 days postpartum) visit
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis is among the live births with HIV test results summarized in the maternal-infant set (the worst outcome summarized for multiple births to the same mother). Analysis used the principle of intent to treat.
Arm/Group Title Antepartum Arm A Antepartum Arm B Antepartum Arm C
Hide Arm/Group Description:
Mothers received ZDV+sdNVP+TRV Tail
Mothers received Triple ARV (3TC-ZDV/LPV-RTV)
Mothers received Triple ARV (FTC-TDF/LPV-RTV)
Overall Number of Participants Analyzed 1386 1385 325
Measure Type: Count of Participants
Unit of Measure: Participants
22
   1.6%
4
   0.3%
2
   0.6%
9.Secondary Outcome
Title Antepartum Component: Overall and HIV-free Infant Survival Through 24 Months of Age (in Conjunction With Infants in the Postpartum Component)
Hide Description This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. Results will be reported to ct.gov when available.
Time Frame Measured through 24 months of age
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Antepartum Component: Adherence to the Maternal Antiretroviral (ARV) Regimen, as Measured by Maternal Report
Hide Description This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. Results will be reported to ct.gov when available.
Time Frame Measured through the Week 1 postpartum study visit
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Antepartum Component: Maternal and Infant Viral Resistance to the Maternal and Infant ARV Strategies
Hide Description This secondary outcome required additional funding for laboratory testing which was not awarded because this outcome was deemed no longer scientifically important, so this outcome is not reported.
Time Frame Measured at the end of the 5-year study period
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Antepartum Component: Cost Effectiveness and Feasibility of the Trial ARV Regimens
Hide Description This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. Results will be reported to ct.gov when available.
Time Frame Measured at the end of the 5-year study period
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Antepartum Component: Maternal HIV RNA Less Than 400 Copies/mL at Delivery
Hide Description Analysis used the principle of intent to treat.
Time Frame Measured at the time of delivery
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis includes only mothers with HIV RNA data at delivery. Analysis used the principle of intent to treat.
Arm/Group Title Antepartum Arm A Antepartum Arm B Antepartum Arm C
Hide Arm/Group Description:
Mothers Received ZDV+sdNVP+TRV Tail
Mothers received Triple ARV (3TC-ZDV/LPV-RTV)
Mothers Received Triple ARV (FTC-TDF/LPV-RTV)
Overall Number of Participants Analyzed 1547 1545 445
Measure Type: Count of Participants
Unit of Measure: Participants
Periods 1 and 2 Number Analyzed 1344 participants 1367 participants 0 participants
HIV RNA < 400 copies/mL
415
  30.9%
1092
  79.9%
HIV RNA >= 400 copies/mL
929
  69.1%
275
  20.1%
Period 2 Number Analyzed 312 participants 321 participants 304 participants
HIV RNA < 400 copies/mL
102
  32.7%
259
  80.7%
225
  74.0%
HIV RNA >= 400 copies/mL
210
  67.3%
62
  19.3%
79
  26.0%
14.Secondary Outcome
Title Antepartum Component: Antepartum Change in HBV DNA Viral Load Between Week 8 and Baseline Levels (Using Log HBV DNA) Among Women With Detectable HBV DNA Viral Loads at Baseline and Other HBV Outcome Measures
Hide Description This secondary outcome required additional funding for laboratory testing. Results will be reported to ct.gov when available.
Time Frame Measured at Week 8
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Postpartum Component: Proportion of Mother-Infant Pairs With no Death or HIV Diagnosis Through 24 Months Post-delivery
Hide Description Defined as infant HIV NAT positivity of a specimen drawn at any post-randomization visit, confirmed by HIV NAT positivity of a second specimen drawn at a different time point, or infant death. Analyses (Kaplan-Meier probabilities) were conducted at the Mother-Infant (M-I) pair level, hence the worst outcome for multiple births was counted as a single event.
Time Frame Measured through 24 months post-delivery
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All M-I pairs, except 1 M-I pair where infant was infected at date of randomization, were included in the analyses. 3 M-I pairs with no post-randomization data were included and censored at the date of randomization. Analyses were intent to treat.
Arm/Group Title Postpartum Arm A (Maternal Prophylaxis) Postpartum Arm B (Infant Prophylaxis)
Hide Arm/Group Description:
Mothers received prophylaxis [preferred regimen: TRV + LPV-RTV]. Infants received short-course NVP.
Infants received extended NVP.
Overall Number of Participants Analyzed 1219 1211
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
0.971
(0.959 to 0.980)
0.977
(0.966 to 0.985)
16.Secondary Outcome
Title Postpartum Component: Proportion of Infants Alive Through 12 and 24 Months Post-delivery
Hide Description Analyses (Kaplan-Meier probabilities) conducted for all individual infants (rather than M-I pair)
Time Frame Measured at 12 and 24 months post-delivery
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All live-born infants were included in the analyses. 4 infants with no post-randomization data were included and censored at the date of randomization in the analyses. Analyses were intent to treat.
Arm/Group Title Postpartum Arm A (Maternal Prophylaxis) Postpartum Arm B (Infant Prophylaxis)
Hide Arm/Group Description:
Mothers received prophylaxis [preferred regimen: TRV + LPV-RTV]. Infants received short-course NVP.
Infants received extended NVP.
Overall Number of Participants Analyzed 1227 1217
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
12 months post delivery
0.988
(0.980 to 0.993)
0.989
(0.981 to 0.994)
24 months post delivery
0.978
(0.967 to 0.986)
0.987
(0.979 to 0.992)
17.Secondary Outcome
Title Postpartum Component: Adherence to the Maternal and/or Infant ARV Regimens, as Measured by Maternal Report and Hair Measures
Hide Description This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. Results will be reported to ct.gov when available.
Time Frame Measured through complete cessation of breastfeeding or 18 months of age, whichever comes first
Outcome Measure Data Not Reported
18.Secondary Outcome
Title Postpartum Component: Rates and Patterns of Maternal and Infant Resistance to the Maternal and Infant ARV Regimens
Hide Description This secondary outcome required additional funding for laboratory testing which was not awarded because this outcome was deemed no longer scientifically important, so this outcome is not reported.
Time Frame Measured at the end of the 5-year study period
Outcome Measure Data Not Reported
19.Secondary Outcome
Title Postpartum Component: Cost-effectiveness and Feasibility of the Study ARV Prophylaxis Regimens
Hide Description This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. Results will be reported to ct.gov when available.
Time Frame Measured at the end of the 5-year study period
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Postpartum Component: Pharmacokinetic Parameters of ARV Drugs Measured in Maternal Plasma, Hair, Breast Milk, and Infant Blood (Plasma or Dried Blood Spot) Samples Collected at Birth; Weeks 1, 6, 14, and 26; and Subsequent Visits During Breastfeeding
Hide Description This secondary outcome required additional funding for laboratory testing. Results will be reported to ct.gov when available.
Time Frame Measured through the last study visit during breastfeeding, or 18 months postpartum, whichever comes first
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Postpartum Component: Functional Maternal Antibody and HIV-envelope Binding Responses in Breast Milk and Plasma, Until Cessation of Breastfeeding or 18 Months Postpartum, Whichever Comes First
Hide Description This secondary outcome required additional funding for laboratory testing. Results will be reported to ct.gov when available.
Time Frame Measured through the time of cessation of breastfeeding or 18 months postpartum, whichever comes first
Outcome Measure Data Not Reported
22.Secondary Outcome
Title Maternal Health Component: Incidence of Death
Hide Description [Not Specified]
Time Frame From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
Arm/Group Title Maternal Health Arm A (Continue Triple ARVs) Maternal Health Arm B (Discontinue Triple ARVs)
Hide Arm/Group Description:
Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Mothers discontinued triple ARV regimen.
Overall Number of Participants Analyzed 797 805
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: New cases per 100 person-years
0.24
(0.18 to 0.32)
0.43
(0.36 to 0.52)
23.Secondary Outcome
Title Maternal Health Component: Incidence of AIDS-defining Illness
Hide Description “AIDS-defining illness” refers to the WHO Clinical Stage 4 illnesses listed in Appendix IV. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.
Time Frame From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
Arm/Group Title Maternal Health Arm A (Continue Triple ARVs) Maternal Health Arm B (Discontinue Triple ARVs)
Hide Arm/Group Description:
Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Mothers discontinued triple ARV regimen.
Overall Number of Participants Analyzed 797 805
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: New cases per 100 person-years
0.08
(0.05 to 0.12)
0.25
(0.20 to 0.30)
24.Secondary Outcome
Title Maternal Health Component: Composite Endpoint of Progression to AIDS-defining Illness, Death, or a Serious Non-AIDS Cardiovascular, Hepatic, or Renal Event
Hide Description This secondary outcome was not included in the primary analyses. Given the results of the primary analyses the protocol team decided that this outcome was no longer scientifically important and resources should not be spent on analyzing it.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
25.Secondary Outcome
Title Maternal Health Component: Incidence of HIV/AIDS-related Events
Hide Description “HIV/AIDS-related event” refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.
Time Frame From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
Arm/Group Title Maternal Health Arm A (Continue Triple ARVs) Maternal Health Arm B (Discontinue Triple ARVs)
Hide Arm/Group Description:
Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Mothers discontinued triple ARV regimen.
Overall Number of Participants Analyzed 797 805
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: New cases per 100 person-years
1.14
(0.89 to 1.45)
1.24
(1.02 to 1.52)
26.Secondary Outcome
Title Maternal Health Component: Number of Cardiovascular or Other Metabolic Events
Hide Description This secondary outcome was not included in the primary analyses. Given the results of the primary analyses the protocol team decided that this outcome was no longer scientifically important and resources should not be spent on analyzing it.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
27.Secondary Outcome
Title Maternal Health Component: Other Targeted Medical Conditions
Hide Description This secondary outcome was not included in the primary analyses. Given the results of the primary analyses the protocol team decided that this outcome was no longer scientifically important and resources should not be spent on analyzing it.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
28.Secondary Outcome
Title Maternal Health Component: Incidence of HIV/AIDS-related Event or Death
Hide Description “HIV/AIDS-related event” refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.
Time Frame From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
Arm/Group Title Maternal Health Arm A (Continue Triple ARVs) Maternal Health Arm B (Discontinue Triple ARVs)
Hide Arm/Group Description:
Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Mothers discontinued triple ARV regimen.
Overall Number of Participants Analyzed 797 805
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: New cases per 100 person-years
1.30
(1.03 to 1.65)
1.43
(1.17 to 1.74)
29.Secondary Outcome
Title Maternal Health Component: Incidence of HIV/AIDS-related Event or World Health Organization (WHO) Clinical Stage 2 or 3 Events
Hide Description “HIV/AIDS-related event” refers to the WHO Clinical Stage 4 illnesses, pulmonary tuberculosis, and other serious bacterial infections listed in Appendix IV of the protocol. Stage 4 illnesses were reviewed and confirmed by an Endpoint review group.
Time Frame From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
Arm/Group Title Maternal Health Arm A (Continue Triple ARVs) Maternal Health Arm B (Discontinue Triple ARVs)
Hide Arm/Group Description:
Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Mothers discontinued triple ARV regimen.
Overall Number of Participants Analyzed 797 805
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: New cases per 100 person-years
3.47
(2.80 to 4.31)
5.61
(4.83 to 6.53)
30.Secondary Outcome
Title Maternal Health Component: Composite Endpoint of Any Condition Outlined in Appendix IV of the Protocol or Death
Hide Description This secondary outcome was not included in the primary analyses. Given the results of the primary analyses the protocol team decided that this outcome was no longer scientifically important and resources should not be spent on analyzing it.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
31.Secondary Outcome
Title Maternal Health Component: Incidence of Tuberculosis
Hide Description Incidence of tuberculosis.
Time Frame From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
Arm/Group Title Maternal Health Arm A (Continue Triple ARVs) Maternal Health Arm B (Discontinue Triple ARVs)
Hide Arm/Group Description:
Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Mothers discontinued triple ARV regimen.
Overall Number of Participants Analyzed 797 805
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: New cases per 100 person-years
0.40
(0.32 to 0.51)
0.31
(0.24 to 0.39)
32.Secondary Outcome
Title Maternal Health Component: Toxicity: Incidence of Grade 3 or Greater Laboratory Results or Signs and Symptoms and Selected Grade 2 Hematologic, Renal, and Hepatic Laboratory Results
Hide Description The maternal safety endpoints summarized include grade 2, 3 or 4 hematologies (hemoglobin (Hb), White Blood Cells (WBC), Absolute Neutrophil Count (ANC), platelet count), chemistries (Alanine Aminotransferase (ALT or SGPT), serum creatinine), and grade 3 or 4 signs and symptoms that occurred post-randomization. These events were graded using the Division of AIDS (DAIDS) AE Grading Table, Version 1.0, December 2004, Clarification August 2009, which is available on the RSC website (http://rsc.tech-res.com).
Time Frame From study entry until July 7, 2015, an average of 94 weeks of follow-up.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes mothers on HAART in the Antepartum component and who were eligible and randomized as part of the Postpartum Component or the Maternal Health Component. Analysis used the intent to treat principle.
Arm/Group Title Maternal Health Arm A (Continue Triple ARVs) Maternal Health Arm B (Discontinue Triple ARVs)
Hide Arm/Group Description:
Mothers continued receiving triple ARV regimen [preferred regimen: TRV + LPV-RTV].
Mothers discontinued triple ARV regimen.
Overall Number of Participants Analyzed 797 805
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: New cases per 100 person-years
15.3
(12.8 to 18.1)
13.9
(11.9 to 16.3)
33.Secondary Outcome
Title Maternal Health Component: Viral Resistance
Hide Description This secondary outcome required additional funding for laboratory testing which was not awarded because this outcome was deemed no longer scientifically important, so this outcome is not reported.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
34.Secondary Outcome
Title Maternal Health Component: Self-reported Adherence
Hide Description This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. Results will be reported to ct.gov when available.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
35.Secondary Outcome
Title Maternal Health Component: Quality of Life
Hide Description This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. Results will be reported to ct.gov when available.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
36.Secondary Outcome
Title Maternal Health Component: Changes in Plasma Concentrations of Inflammatory and Thrombogenic Markers
Hide Description This secondary outcome was not included in the primary analyses. Given the results of the primary analyses the protocol team decided that this outcome was no longer scientifically important and resources should not be spent on analyzing it.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
37.Secondary Outcome
Title Maternal Health Component: Cost-effectiveness
Hide Description This secondary outcome was not included in the primary analyses and will be defined in more detail in a separate analysis plan. Results will be reported to ct.gov when available.
Time Frame From study entry until July 7, 2015.
Outcome Measure Data Not Reported
Time Frame From study entry (for mothers) or birth (for infants) until study completion on September 30, 2016, an average of 169 weeks for mothers and through 24 months or September 30, 2016 for infants, whichever came first.
Adverse Event Reporting Description Some women lost their infant before delivery. Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities requiring hospitalization and all grade 2 and higher hematology or chemistry events and grade 3 or 4 sign or symptoms. These events were graded using the DAIDS AE Grading Table, Version 1.0, 2009, available on the RSC website (http://rsc.tech-res.com).
 
Arm/Group Title Mother, (AP) ZDV+sdNVP+TRV Tail Mother, (AP) Triple ARV (3TC-ZDV/LPV-RTV) Mother, (AP) Triple ARV (FTC-TDF/LPV-RTV) Mother, LP Infant, (Mother Received ZDV+sdNVP+TRV Tail) Infant, (Mother Received Triple ARV (3TC-ZDV/LPV-RTV)) Infant, (Mother Received Triple ARV (FTC-TDF/LPV-RTV)) Infant, LP
Hide Arm/Group Description Mothers received ZDV+sdNVP+TRV tail Mothers received Triple ARV (3TC-ZDV/LPV-RTV) Mothers received Triple ARV (FTC-TDF/LPV-RTV) Registrational component to assess entry criteria for possible randomization in the Postpartum Component Mothers received ZDV+sdNVP+TRV tail Mothers received Triple ARV (3TC-ZDV/LPV-RTV) Mothers received Triple ARV (FTC-TDF/LPV-RTV) Registrational component to assess entry criteria for possible randomization in the Postpartum Component
All-Cause Mortality
Mother, (AP) ZDV+sdNVP+TRV Tail Mother, (AP) Triple ARV (3TC-ZDV/LPV-RTV) Mother, (AP) Triple ARV (FTC-TDF/LPV-RTV) Mother, LP Infant, (Mother Received ZDV+sdNVP+TRV Tail) Infant, (Mother Received Triple ARV (3TC-ZDV/LPV-RTV)) Infant, (Mother Received Triple ARV (FTC-TDF/LPV-RTV)) Infant, LP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/1547 (0.58%)   14/1545 (0.91%)   2/445 (0.45%)   3/204 (1.47%)   59/1500 (3.93%)   46/1478 (3.11%)   27/429 (6.29%)   5/204 (2.45%) 
Show Serious Adverse Events Hide Serious Adverse Events
Mother, (AP) ZDV+sdNVP+TRV Tail Mother, (AP) Triple ARV (3TC-ZDV/LPV-RTV) Mother, (AP) Triple ARV (FTC-TDF/LPV-RTV) Mother, LP Infant, (Mother Received ZDV+sdNVP+TRV Tail) Infant, (Mother Received Triple ARV (3TC-ZDV/LPV-RTV)) Infant, (Mother Received Triple ARV (FTC-TDF/LPV-RTV)) Infant, LP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   267/1547 (17.26%)   276/1545 (17.86%)   69/445 (15.51%)   10/204 (4.90%)   296/1500 (19.73%)   287/1478 (19.42%)   113/429 (26.34%)   20/204 (9.80%) 
Blood and lymphatic system disorders                 
Anaemia  1  13/1547 (0.84%)  16/1545 (1.04%)  4/445 (0.90%)  3/204 (1.47%)  10/1500 (0.67%)  11/1478 (0.74%)  0/429 (0.00%)  0/204 (0.00%) 
Immune thrombocytopenic purpura  1  1/1547 (0.06%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Iron deficiency anaemia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  1/204 (0.49%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Neutropenia  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  4/1500 (0.27%)  2/1478 (0.14%)  0/429 (0.00%)  0/204 (0.00%) 
Thrombocytopenia  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Cardiac disorders                 
Extrasystoles  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Pulmonary valve stenosis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital, familial and genetic disorders                 
Ankyloglossia congenital  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Atrial septal defect  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Cleft palate  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Congenital anaemia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital anomaly  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  1/429 (0.23%)  0/204 (0.00%) 
Congenital genital malformation male  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital inguinal hernia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital malaria  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital megacolon  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital musculoskeletal anomaly  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital pneumonia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  3/1478 (0.20%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital rubella infection  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Congenital syphilis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  2/1478 (0.14%)  0/429 (0.00%)  0/204 (0.00%) 
Congenital umbilical hernia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Craniosynostosis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Dermoid cyst  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Developmental hip dysplasia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Exomphalos  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Gastroschisis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Genitalia external ambiguous  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Heart disease congenital  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  0/429 (0.00%)  1/204 (0.49%) 
Holoprosencephaly  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hypospadias  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  2/1478 (0.14%)  0/429 (0.00%)  0/204 (0.00%) 
Laryngomalacia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Macrocephaly  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Meningomyelocele  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  2/1478 (0.14%)  1/429 (0.23%)  0/204 (0.00%) 
Micrognathia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Multiple congenital abnormalities  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Multiple gastrointestinal atresias  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Patent ductus arteriosus  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  2/1478 (0.14%)  0/429 (0.00%)  1/204 (0.49%) 
Persistent foetal circulation  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Sickle cell anaemia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Talipes  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  1/1478 (0.07%)  1/429 (0.23%)  0/204 (0.00%) 
Trisomy 21  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Ventricular septal defect  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  1/429 (0.23%)  0/204 (0.00%) 
Eye disorders                 
Cataract  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Conjunctival haemorrhage  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Strabismus  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Gastrointestinal disorders                 
Abdominal distension  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Abdominal mass  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Abdominal pain  1  4/1547 (0.26%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Abdominal pain lower  1  4/1547 (0.26%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Ascites  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Diarrhoea  1  1/1547 (0.06%)  3/1545 (0.19%)  0/445 (0.00%)  0/204 (0.00%)  3/1500 (0.20%)  3/1478 (0.20%)  1/429 (0.23%)  0/204 (0.00%) 
Femoral hernia  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Gastritis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Haemorrhoids  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Ileus  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Ileus paralytic  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Intestinal obstruction  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  1/204 (0.49%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Necrotising colitis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  6/1500 (0.40%)  3/1478 (0.20%)  0/429 (0.00%)  0/204 (0.00%) 
Peptic ulcer  1  1/1547 (0.06%)  1/1545 (0.06%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Rectal haemorrhage  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Small intestinal obstruction  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Umbilical hernia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Vomiting  1  1/1547 (0.06%)  1/1545 (0.06%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
General disorders                 
Death  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  4/1500 (0.27%)  4/1478 (0.27%)  3/429 (0.70%)  1/204 (0.49%) 
Infusion site extravasation  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Pyrexia  1  1/1547 (0.06%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  3/1500 (0.20%)  4/1478 (0.27%)  0/429 (0.00%)  0/204 (0.00%) 
Sudden infant death syndrome  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hepatobiliary disorders                 
Autoimmune hepatitis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Cholecystitis acute  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Drug-induced liver injury  1  0/1547 (0.00%)  3/1545 (0.19%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hepatic function abnormal  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hepatitis  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Hepatotoxicity  1  0/1547 (0.00%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Hyperbilirubinaemia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Jaundice  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Jaundice cholestatic  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Infections and infestations                 
Abscess  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Abscess neck  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Amniotic cavity infection  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Anal abscess  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Appendicitis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Arthritis bacterial  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Bacteraemia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Bacterial infection  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Bacterial sepsis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  3/1500 (0.20%)  3/1478 (0.20%)  2/429 (0.47%)  0/204 (0.00%) 
Bartholin's abscess  1  4/1547 (0.26%)  3/1545 (0.19%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Brain abscess  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Breast abscess  1  1/1547 (0.06%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Bronchiolitis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  8/1500 (0.53%)  8/1478 (0.54%)  0/429 (0.00%)  1/204 (0.49%) 
Bullous impetigo  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Cellulitis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Cervicitis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Conjunctivitis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Disseminated tuberculosis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Dysentery  1  0/1547 (0.00%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Encephalitis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Enterobacter sepsis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Gastroenteritis  1  5/1547 (0.32%)  10/1545 (0.65%)  1/445 (0.22%)  0/204 (0.00%)  29/1500 (1.93%)  26/1478 (1.76%)  8/429 (1.86%)  2/204 (0.98%) 
Giardiasis  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Lower respiratory tract infection  1  3/1547 (0.19%)  3/1545 (0.19%)  0/445 (0.00%)  0/204 (0.00%)  6/1500 (0.40%)  1/1478 (0.07%)  1/429 (0.23%)  0/204 (0.00%) 
Malaria  1  9/1547 (0.58%)  6/1545 (0.39%)  4/445 (0.90%)  0/204 (0.00%)  4/1500 (0.27%)  9/1478 (0.61%)  3/429 (0.70%)  1/204 (0.49%) 
Measles  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Meningitis  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  0/429 (0.00%)  1/204 (0.49%) 
Meningitis bacterial  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  2/1478 (0.14%)  0/429 (0.00%)  0/204 (0.00%) 
Meningitis cryptococcal  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Meningitis tuberculous  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Meningitis viral  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Neonatal pneumonia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  2/1478 (0.14%)  0/429 (0.00%)  0/204 (0.00%) 
Neurosyphilis  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Ophthalmia neonatorum  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  1/1478 (0.07%)  1/429 (0.23%)  0/204 (0.00%) 
Otitis media  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Pelvic abscess  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Pelvic infection  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Pelvic inflammatory disease  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Pertussis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Pharyngitis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Plasmodium falciparum infection  1  5/1547 (0.32%)  2/1545 (0.13%)  1/445 (0.22%)  0/204 (0.00%)  7/1500 (0.47%)  5/1478 (0.34%)  0/429 (0.00%)  0/204 (0.00%) 
Plasmodium malariae infection  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Pneumonia  1  2/1547 (0.13%)  5/1545 (0.32%)  0/445 (0.00%)  0/204 (0.00%)  34/1500 (2.27%)  33/1478 (2.23%)  8/429 (1.86%)  6/204 (2.94%) 
Pneumonia bacterial  1  3/1547 (0.19%)  4/1545 (0.26%)  0/445 (0.00%)  0/204 (0.00%)  23/1500 (1.53%)  15/1478 (1.01%)  5/429 (1.17%)  0/204 (0.00%) 
Post procedural sepsis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Postoperative wound infection  1  0/1547 (0.00%)  1/1545 (0.06%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Postpartum sepsis  1  3/1547 (0.19%)  2/1545 (0.13%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Pulmonary tuberculosis  1  1/1547 (0.06%)  3/1545 (0.19%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  1/429 (0.23%)  0/204 (0.00%) 
Pyelonephritis  1  2/1547 (0.13%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Respiratory tract infection  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Rhinitis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  2/1478 (0.14%)  0/429 (0.00%)  0/204 (0.00%) 
Salmonella sepsis  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Salpingitis  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Sepsis  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  9/1500 (0.60%)  3/1478 (0.20%)  2/429 (0.47%)  0/204 (0.00%) 
Sepsis neonatal  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  47/1500 (3.13%)  33/1478 (2.23%)  11/429 (2.56%)  3/204 (1.47%) 
Sexually transmitted disease  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Staphylococcal scalded skin syndrome  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Staphylococcal sepsis  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  1/429 (0.23%)  0/204 (0.00%) 
Staphylococcal skin infection  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Subcutaneous abscess  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Tuberculosis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Upper respiratory tract infection  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  1/429 (0.23%)  0/204 (0.00%) 
Urinary tract infection  1  12/1547 (0.78%)  8/1545 (0.52%)  4/445 (0.90%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Vaginal infection  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Viral infection  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Vulvovaginitis  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Vulvovaginitis trichomonal  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Wound infection  1  0/1547 (0.00%)  1/1545 (0.06%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Wound sepsis  1  1/1547 (0.06%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Injury, poisoning and procedural complications                 
Abdominal wound dehiscence  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Ankle fracture  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Bladder injury  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Burns first degree  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Burns second degree  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Clavicle fracture  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Femur fracture  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Forearm fracture  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Head injury  1  2/1547 (0.13%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  2/429 (0.47%)  0/204 (0.00%) 
Herbal toxicity  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Humerus fracture  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Lower limb fracture  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Multiple injuries  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Penetrating abdominal trauma  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Post procedural complication  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Postoperative wound complication  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Road traffic accident  1  1/1547 (0.06%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Soft tissue injury  1  2/1547 (0.13%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Thermal burn  1  0/1547 (0.00%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  3/1478 (0.20%)  0/429 (0.00%)  0/204 (0.00%) 
Traumatic fracture  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Uterine dehiscence  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Uterine rupture  1  1/1547 (0.06%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Vaginal laceration  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Wound dehiscence  1  1/1547 (0.06%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Investigations                 
Alanine aminotransferase increased  1  0/1547 (0.00%)  5/1545 (0.32%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Amniotic fluid volume decreased  1  0/1547 (0.00%)  4/1545 (0.26%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Aspartate aminotransferase increased  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Blood creatinine increased  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Foetal non-stress test abnormal  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Haemoglobin decreased  1  1/1547 (0.06%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hepatic enzyme increased  1  0/1547 (0.00%)  2/1545 (0.13%)  0/445 (0.00%)  1/204 (0.49%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Liver function test increased  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Neutrophil count decreased  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Transaminases increased  1  0/1547 (0.00%)  2/1545 (0.13%)  0/445 (0.00%)  1/204 (0.49%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Weight decreased  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Metabolism and nutrition disorders                 
Dehydration  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Diabetes mellitus  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Diabetic ketoacidosis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Failure to thrive  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  1/204 (0.49%) 
Hypoglycaemia  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hypoglycaemia neonatal  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Malnutrition  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  22/1500 (1.47%)  20/1478 (1.35%)  11/429 (2.56%)  2/204 (0.98%) 
Marasmus  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  1/204 (0.49%) 
Poor feeding infant  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Vitamin K deficiency  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Intervertebral disc protrusion  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Joint hyperextension  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Symphysiolysis  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Nervous system disorders                 
Aphasia  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Cerebral infarction  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Cerebrovascular accident  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  1/204 (0.49%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Convulsion neonatal  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Dizziness  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Encephalopathy neonatal  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Facial paralysis  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Febrile convulsion  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Generalised tonic-clonic seizure  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Headache  1  1/1547 (0.06%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hemiparesis  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Hydrocephalus  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hypoxic-ischaemic encephalopathy  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  1/1478 (0.07%)  2/429 (0.47%)  0/204 (0.00%) 
Migraine  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Seizure  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  2/1500 (0.13%)  1/1478 (0.07%)  0/429 (0.00%)  0/204 (0.00%) 
Pregnancy, puerperium and perinatal conditions                 
Abortion  1  1/1547 (0.06%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Abortion complete  1  1/1547 (0.06%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Abortion incomplete  1  4/1547 (0.26%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Abortion missed  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  1/204 (0.49%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Abortion spontaneous  1  7/1547 (0.45%)  5/1545 (0.32%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Abortion threatened  1  2/1547 (0.13%)  1/1545 (0.06%)  2/445 (0.45%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Eclampsia  1  0/1547 (0.00%)  2/1545 (0.13%)  2/445 (0.45%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Ectopic pregnancy  1  2/1547 (0.13%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
False labour  1  2/1547 (0.13%)  4/1545 (0.26%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Foetal death  1  25/1547 (1.62%)  37/1545 (2.39%)  7/445 (1.57%)  1/204 (0.49%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Foetal distress syndrome  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Foetal growth restriction  1  5/1547 (0.32%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Foetal hypokinesia  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Gestational diabetes  1  0/1547 (0.00%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Gestational hypertension  1  18/1547 (1.16%)  9/1545 (0.58%)  6/445 (1.35%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
HELLP syndrome  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Haemorrhage in pregnancy  1  9/1547 (0.58%)  4/1545 (0.26%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Hyperemesis gravidarum  1  0/1547 (0.00%)  1/1545 (0.06%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Intrapartum haemorrhage  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Jaundice neonatal  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  6/1500 (0.40%)  2/1478 (0.14%)  1/429 (0.23%)  0/204 (0.00%) 
Labour pain  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Low birth weight baby  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  3/1500 (0.20%)  6/1478 (0.41%)  5/429 (1.17%)  0/204 (0.00%) 
Meconium in amniotic fluid  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  1/1500 (0.07%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Obstructed labour  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Oligohydramnios  1  3/1547 (0.19%)  4/1545 (0.26%)  2/445 (0.45%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Peripartum cardiomyopathy  1  1/1547 (0.06%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Placenta accreta  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Placenta praevia  1  1/1547 (0.06%)  2/1545 (0.13%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Placental insufficiency  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Polyhydramnios  1  0/1547 (0.00%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Postpartum haemorrhage  1  11/1547 (0.71%)  11/1545 (0.71%)  2/445 (0.45%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Pre-eclampsia  1  15/1547 (0.97%)  16/1545 (1.04%)  3/445 (0.67%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Premature baby  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  25/1500 (1.67%)  42/1478 (2.84%)  19/429 (4.43%)  0/204 (0.00%) 
Premature delivery  1  9/1547 (0.58%)  4/1545 (0.26%)  3/445 (0.67%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Premature labour  1  16/1547 (1.03%)  15/1545 (0.97%)  8/445 (1.80%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Premature rupture of membranes  1  10/1547 (0.65%)  14/1545 (0.91%)  2/445 (0.45%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Premature separation of placenta  1  6/1547 (0.39%)  2/1545 (0.13%)  2/445 (0.45%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Preterm premature rupture of membranes  1  7/1547 (0.45%)  4/1545 (0.26%)  3/445 (0.67%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Prolonged labour  1  0/1547 (0.00%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Prolonged pregnancy  1  1/1547 (0.06%)  0/1545 (0.00%)  1/445 (0.22%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Prolonged rupture of membranes  1  0/1547 (0.00%)  0/1545 (0.00%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  1/429 (0.23%)  0/204 (0.00%) 
Retained placenta or membranes  1  2/1547 (0.13%)  1/1545 (0.06%)  0/445 (0.00%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%) 
Retained products of conception  1  6/1547 (0.39%)  4/1545 (0.26%)  2/445 (0.45%)  0/204 (0.00%)  0/1500 (0.00%)  0/1478 (0.00%)  0/429 (0.00%)  0/204 (0.00%)