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Trial record 2 of 2 for:    15627034 [PUBMED-IDS]

Comparison of Three Anti-HIV Regimens to Prevent Nevirapine Resistance in Women Who Take Nevirapine During Pregnancy

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ClinicalTrials.gov Identifier: NCT00099632
Recruitment Status : Completed
First Posted : December 20, 2004
Results First Posted : January 19, 2012
Last Update Posted : February 2, 2016
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: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Emtricitabine/Tenofovir Disoproxil Fumarate
Drug: Lamivudine/Zidovudine
Drug: Lopinavir/Ritonavir
Drug: single dose Nevirapine
Enrollment 484

Recruitment Details Study participants were recruited at 8 sites: 2 from South Africa, 2 from India, and 1 each from Haiti, Uganda, Tanzania, and Malawi, between January 2007 to October 2009.
Pre-assignment Details

62 participants who randomized but did not start study treatment were excluded from the analysis. These 62 participants were either off study prior to delivery or delivered on study but did not take any dose of study treatment.

All the analyses were restricted to the 422 women who received study treatment.

Arm/Group Title 7-day Lamivudine/Zidovudine (3TC/ZDV) 21-day Lamivudine/Zidovudine (3TC/ZDV) 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 7-day Lopinavir/Ritonavir (LPV/r) 21-day Lopinavir/Ritonavir (LPV/r)
Hide Arm/Group Description SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV. SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV. SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF. SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF. SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r. SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Period Title: Overall Study
Started 73 68 75 67 71 68
Completed 72 67 72 66 70 66
Not Completed 1 1 3 1 1 2
Reason Not Completed
Lost to Follow-up             1             0             3             1             1             0
Withdrawal by Subject             0             1             0             0             0             1
Protocol Violation             0             0             0             0             0             1
Arm/Group Title 7-day Lamivudine/Zidovudine (3TC/ZDV) 21-day Lamivudine/Zidovudine (3TC/ZDV) 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 7-day Lopinavir/Ritonavir (LPV/r) 21-day Lopinavir/Ritonavir (LPV/r) Total
Hide Arm/Group Description SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV. SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV. SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF. SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF. SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r. SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r Total of all reporting groups
Overall Number of Baseline Participants 73 68 75 67 71 68 422
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
27  (6) 27  (5) 26  (5) 26  (5) 27  (6) 26  (5) 27  (5)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
Between 13 and 19 years 2 1 5 3 3 3 17
Between 20 and 29 years 49 46 53 46 47 48 289
Between 30 and 39 years 20 20 16 18 19 16 109
>= 40 years 2 1 1 0 2 1 7
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
Female
73
 100.0%
68
 100.0%
75
 100.0%
67
 100.0%
71
 100.0%
68
 100.0%
422
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
Haiti 12 11 10 7 9 9 58
Tanzania 3 1 3 3 2 2 14
Uganda 17 16 18 17 17 16 101
South Africa 13 8 10 9 10 10 60
Malawi 13 14 14 12 17 15 85
India 15 18 20 19 16 16 104
Gestational age at NVP dosing, Continuous  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
38  (2) 39  (2) 38  (2) 38  (3) 38  (2) 38  (2) 38  (2)
Screening CD4 count Categorical  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
250-349 cells/mm^3 15 7 8 6 20 13 69
350-499 cells/mm^3 24 21 29 29 25 22 150
>=500 cells/mm^3 34 40 38 32 26 33 203
Screening CD4 count Continuous  
Mean (Standard Deviation)
Unit of measure:  Cells/mm^3
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
538  (244) 585  (215) 537  (186) 545  (191) 505  (205) 566  (249) 545  (216)
Screening HIV-1 RNA Categorical  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
<=400 copies/mL 17 13 13 12 12 16 83
401-999 copies/mL 12 8 7 11 6 4 48
1000-9999 copies/mL 17 26 33 25 29 18 148
10000-99999 copies/mL 17 17 18 14 20 26 112
100000-749999 copies/mL 8 3 4 5 4 4 28
>=750000 copies/mL 1 0 0 0 0 0 1
Missing/Unknown 1 1 0 0 0 0 2
Screening HIV-1 RNA Continuous  
Mean (Standard Deviation)
Unit of measure:  Log10 copies/mL
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
3.50  (1.01) 3.55  (0.90) 3.54  (0.82) 3.50  (0.88) 3.63  (0.90) 3.66  (0.92) 3.56  (0.90)
Actual ZDV exposure during pregnancy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 73 participants 68 participants 75 participants 67 participants 71 participants 68 participants 422 participants
yes 46 47 47 42 43 42 267
no 27 21 28 25 28 26 155
1.Primary Outcome
Title Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping
Hide Description

For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed to the primary endpoint; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed to primary endpoint.

10 participants who did not have resistance samples available were excluded from the primary endpoint analysis.

Time Frame 2 and 6 weeks after completion of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
412 women with primary endpoint results available
Arm/Group Title 7-day Lamivudine/Zidovudine (3TC/ZDV) 21-day Lamivudine/Zidovudine (3TC/ZDV) 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 7-day Lopinavir/Ritonavir (LPV/r) 21-day Lopinavir/Ritonavir (LPV/r)
Hide Arm/Group Description:
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Overall Number of Participants Analyzed 73 67 71 65 71 65
Measure Type: Number
Unit of Measure: participants
1 0 0 0 3 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 7-day Lamivudine/Zidovudine (3TC/ZDV), 21-day Lamivudine/Zidovudine (3TC/ZDV), 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), 7-day Lopinavir/Ritonavir (LPV/r), 21-day Lopinavir/Ritonavir (LPV/r)
Comments Compare proportion of women with new NNRTI-resistant variants between treatment durations (7-day vs. 21 day), pooled over ARV regimens (3TC/ZDV, FTC/TDF, and LPV/r), stratified by ARV regimen and the actual receipt of antenatal ZDV
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by ARV regimen and the actual receipt of antenatal ZDV
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 7-day Lamivudine/Zidovudine (3TC/ZDV), 21-day Lamivudine/Zidovudine (3TC/ZDV), 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), 7-day Lopinavir/Ritonavir (LPV/r), 21-day Lopinavir/Ritonavir (LPV/r)
Comments Compare proportion of women with new NNRTI-resistant variants among ARV regimens (3TC/ZDV vs. FTC/TDF vs. LPV/r), pooled over treatment durations 7-day and 21-day, stratified by treatment duration and the actual receipt of antenatal ZDV
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by treatment duration and the actual receipt of antenatal ZDV
2.Secondary Outcome
Title Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping.
Hide Description For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed.
Time Frame 2 and 6 weeks after completion of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 7-day Lamivudine/Zidovudine (3TC/ZDV) 21-day Lamivudine/Zidovudine (3TC/ZDV) 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 7-day Lopinavir/Ritonavir (LPV/r) 21-day Lopinavir/Ritonavir (LPV/r)
Hide Arm/Group Description:
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Overall Number of Participants Analyzed 73 67 71 65 71 65
Measure Type: Number
Unit of Measure: participants
0 1 1 1 1 0
3.Secondary Outcome
Title Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping.
Hide Description For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed.
Time Frame 2 and 6 weeks after completion of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 7-day Lamivudine/Zidovudine (3TC/ZDV) 21-day Lamivudine/Zidovudine (3TC/ZDV) 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 7-day Lopinavir/Ritonavir (LPV/r) 21-day Lopinavir/Ritonavir (LPV/r)
Hide Arm/Group Description:
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Overall Number of Participants Analyzed 73 67 71 65 71 65
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0 0
4.Secondary Outcome
Title Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12
Hide Description

Grade 3 or higher signs and symptoms, laboratory abnormalities, events that are reported through the EAE system, and any grade event that leads to a treatment change from first day of study treatment to week 12.

Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death

Time Frame From first day of study treatment to week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 7-day Lamivudine/Zidovudine (3TC/ZDV) 21-day Lamivudine/Zidovudine (3TC/ZDV) 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 7-day Lopinavir/Ritonavir (LPV/r) 21-day Lopinavir/Ritonavir (LPV/r)
Hide Arm/Group Description:
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Overall Number of Participants Analyzed 73 68 75 67 71 68
Measure Type: Number
Unit of Measure: participants
5 1 1 0 2 2
5.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Prematurely
Hide Description participants assigned to 7-day treatment arm and 21-day treatment arm were supposed to stay in study treatment for 7 days and 21 days respectively.
Time Frame From first day of study treatment to last day of study treatment (up to 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 7-day Lamivudine/Zidovudine (3TC/ZDV) 21-day Lamivudine/Zidovudine (3TC/ZDV) 7-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 21-day Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) 7-day Lopinavir/Ritonavir (LPV/r) 21-day Lopinavir/Ritonavir (LPV/r)
Hide Arm/Group Description:
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Overall Number of Participants Analyzed 73 68 75 67 71 63
Measure Type: Number
Unit of Measure: participants
0 2 0 0 0 5
Time Frame From first treatment date to 12 weeks of follow up.
Adverse Event Reporting Description Expedited adverse event(AE) reporting followed intensive DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and >=3 grade 3 AEs defined by the "DAIDS Table for Grading the Severity of Adult and Pediatric AEs".
 
Arm/Group Title 7-day 3TC/ZDV 21-day 3TC/ZDV 7-day FTC/TDF 21-day FTC/TDF 7-day LPV/r 21-day LPV/r
Hide Arm/Group Description SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r SD NVP and LPV/r provided at onset of active labor, followed by 21 days of LPV/r
All-Cause Mortality
7-day 3TC/ZDV 21-day 3TC/ZDV 7-day FTC/TDF 21-day FTC/TDF 7-day LPV/r 21-day LPV/r
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
7-day 3TC/ZDV 21-day 3TC/ZDV 7-day FTC/TDF 21-day FTC/TDF 7-day LPV/r 21-day LPV/r
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/73 (2.74%)   0/68 (0.00%)   1/75 (1.33%)   0/67 (0.00%)   1/71 (1.41%)   0/68 (0.00%) 
Blood and lymphatic system disorders             
Anaemia  1  1/73 (1.37%)  0/68 (0.00%)  0/75 (0.00%)  0/67 (0.00%)  0/71 (0.00%)  0/68 (0.00%) 
Injury, poisoning and procedural complications             
Uterine rupture  1  1/73 (1.37%)  0/68 (0.00%)  0/75 (0.00%)  0/67 (0.00%)  0/71 (0.00%)  0/68 (0.00%) 
Pregnancy, puerperium and perinatal conditions             
Intra-uterine death  1  0/73 (0.00%)  0/68 (0.00%)  1/75 (1.33%)  0/67 (0.00%)  1/71 (1.41%)  0/68 (0.00%) 
Stillbirth  1  1/73 (1.37%)  0/68 (0.00%)  0/75 (0.00%)  0/67 (0.00%)  0/71 (0.00%)  0/68 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
7-day 3TC/ZDV 21-day 3TC/ZDV 7-day FTC/TDF 21-day FTC/TDF 7-day LPV/r 21-day LPV/r
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/73 (0.00%)   0/68 (0.00%)   0/75 (0.00%)   0/67 (0.00%)   0/71 (0.00%)   0/68 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
Results Point of Contact
Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
Phone: (617) 432-2829
Publications of Results:
McMahon D, Noel F, Zheng L, Kabanda J, Halvas E, Taulo F, Kumarasamy N, Wallis C, Hughes M, Mellors J. Suppression of NVP Resistance with 7- vs 21-day ARV Regimens after Single-dose NVP: Results of A5207. Presented at 18th Conference on Retroviruses & Opportunistic Infections (CROI 11) on 03/01/2011 at Boston, MA
Hong F, Halvas E, Chan E, Zheng L, Hughes M, Hitti J, McMahon D, Mellors J. Suppression of Minor NVP-Resistant Variants With 7- vs. 21-Day Antiretroviral Regimens After Single Dose Nevirapine. Presented at 20th Anniversary of the International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies on Jun 9, 2011, Los Cabos, Mexico
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00099632     History of Changes
Other Study ID Numbers: A5207
10127 ( Registry Identifier: DAIDS ES )
ACTG A5207
MOMS
First Submitted: December 17, 2004
First Posted: December 20, 2004
Results First Submitted: December 6, 2011
Results First Posted: January 19, 2012
Last Update Posted: February 2, 2016