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Daily Isoniazid to Prevent Tuberculosis in Infants Born to Mothers With HIV

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ClinicalTrials.gov Identifier: NCT00080119
Recruitment Status : Terminated (Data Safety Monitoring Board (DSMB) recommended stopping study due to futility)
First Posted : March 25, 2004
Results First Posted : October 19, 2010
Last Update Posted : February 14, 2011
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Comprehensive International Program of Research on AIDS
Secure the Future Foundation
Information provided by:
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Conditions HIV Infection
Tuberculosis
Pneumocystis Jiroveci Pneumonia
Interventions Drug: Isoniazid (INH)
Drug: Trimethoprim/Sulfamethoxazole (TMP/SMX)
Drug: Isoniazid Placebo (PL)
Enrollment 1354
Recruitment Details Study participants were recruited at four study sites, three in South Africa and one in Botswana, between December 13, 2004 and June 26, 2008
Pre-assignment Details Infants perinatally exposed to HIV 91-120 days with documented receipt of Bacille Calmette-Guerin (BCG) vaccine by 30 days (>=90 days since receipt), no previous diagnosis or treatment of TB or contact with known TB case, stratified by HIV and randomized to receive blinded INH or INH placebo. 3 participants randomized but did not start treatment.
Arm/Group Title HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Hide Arm/Group Description Perinatally exposed, HIV-uninfected (HIVneg) children receiving Isoniazid (INH)10-20 mg/kg orally once a day for 96 weeks + Trimethoprim/Sulfamethoxazole (TMP/SMX) 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding Perinatally-exposed, HIV-uninfected (HIVneg) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding HIV-infected (HIVpos) children receiving Isoniazid (INH) 10-20 mg/kg orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines. HIV-infected (HIVpos) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines.
Period Title: Overall Study
Started 403 401 273 274
Completed 347 339 108 111
Not Completed 56 62 165 163
Reason Not Completed
Discontinued because of study closure             0             0             130             141
Unable to get to clinic             24             24             7             1
Consent withdrawn             13             17             4             6
Unwilling to adhere to study requirement             3             2             5             1
Lost to Follow-up             16             19             19             14
Arm/Group Title HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL Total
Hide Arm/Group Description Perinatally exposed, HIV-uninfected (HIVneg) children receiving Isoniazid (INH)10-20 mg/kg orally once a day for 96 weeks + Trimethoprim/Sulfamethoxazole (TMP/SMX) 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding Perinatally-exposed, HIV-uninfected (HIVneg) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding HIV-infected (HIVpos) children receiving Isoniazid (INH) 10-20 mg/kg orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines. HIV-infected (HIVpos) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines. Total of all reporting groups
Overall Number of Baseline Participants 403 401 273 274 1351
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
91-100 days 258 253 171 192 874
101-110 days 71 84 56 33 244
111-120 days 74 64 46 49 233
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Female
203
  50.4%
190
  47.4%
159
  58.2%
151
  55.1%
703
  52.0%
Male
200
  49.6%
211
  52.6%
114
  41.8%
123
  44.9%
648
  48.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Indigenous African 389 386 264 272 1311
Mixed ancestry/other 14 15 9 2 40
Age at receipt of Bacille Calmette-Guerin (BCG) vaccination (days)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
<= 7 days 395 392 255 258 1300
8-29 days 8 9 18 16 51
Any smoker in household  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Yes 191 177 120 131 619
No 211 224 153 141 729
Missing 1 0 0 2 3
Birth weight (grams)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
<2500 grams 49 49 68 56 222
>= 2500 grams 354 352 205 218 1129
CD4%   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
<20% 0 0 56 55 111
20%-<25% 0 0 40 46 86
>= 25% 0 0 162 157 319
Missing 0 0 14 13 27
Not applicable 403 401 1 3 808
[1]
Measure Description: Only for HIV-infected participants. Those in the HIV-infected stratum that were later determined to be HIV-uninfected are recorded as not applicable.
Centers for Disease Control (CDC) Disease Category   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Category N or A 0 0 252 244 496
Category B 0 0 16 21 37
Category C 0 0 2 3 5
HIV-uninfected on repeat test 0 0 1 3 4
Missing 0 0 2 3 5
Not applicable (HIV-uninfected) 403 401 0 0 804
[1]
Measure Description: Only for HIV-infected participants.
Caregiver currently smokes  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Yes 11 25 16 10 62
No 392 376 257 264 1289
Ever breastfed  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Yes 24 24 37 36 121
No 379 377 236 238 1230
HIV-1 RNA (copies/ml)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
<= 400 copies/ml 0 0 8 12 20
401 - <20,000 copies/ml 0 0 36 51 87
20,000 - < 750,000 copies/ml 0 0 91 86 177
>= 750,000 copies/ml 0 0 129 116 245
Missing 0 0 8 6 14
Not applicable 403 401 1 3 808
[1]
Measure Description: Only for HIV-infected participants. Those in the HIV-infected stratum that were later determined to be HIV-uninfected are recorded as not applicable.
History of tuberculosis (TB) in mother  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Yes 33 25 14 25 97
No 370 376 259 249 1254
Housing  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Formal (brick) house 235 233 162 183 813
Informal (shack/wooden) 168 168 109 89 534
Hostel 0 0 2 0 2
Missing 0 0 0 2 2
On antiretrovirals at entry   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Yes 0 0 78 93 171
No 0 0 194 178 372
Not applicable 403 401 1 3 808
[1]
Measure Description: Only for HIV-infected participants. Those in the HIV-infected stratum that were later determined to be HIV-uninfected are recorded as not applicable.
Site of enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 403 participants 401 participants 273 participants 274 participants 1351 participants
Johannesburg, S Africa 259 260 180 179 878
Cape Town, S Africa 140 138 66 65 409
Durban, S Africa 4 3 26 27 60
Gaborone, Botswana 0 0 1 3 4
1.Primary Outcome
Title Time to Development of Tuberculosis (TB) Disease or Death Among HIV-infected Children
Hide Description Criteria for diagnosis with TB disease: Definite-isolation of Mycobacterium TB (M.tb) or +ve stain on cerebrospinal fluid (CSF); Probable- +ve acid fast bacilli (AFB) stain on fluids/tissues other than CSF and sufficient clinical criteria/radiographic evidence suggestive of TB; Possible-abnormal chest radiograph suggestive of pulmonary TB (PTB) and either a +ve tuberculin skin test (TST) or minimum score on algorithm for clinical TB. Records reviewed by Endpoint Review Group. Results report percent of participants reaching TB disease/death by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes HIVpos who started study treatment. Time from randomization to TB disease/death was calculated. Participants lost-to-follow-up (LTF) <96 wks (+12wks) censored at the time of LTF. Participants in follow-up at 96 wks free of TB disease censored at 96 wks. Participants on study when study discontinued censored at discontinuation visit.
Arm/Group Title HIVpos/INH HIVpos/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 273 274
Measure Type: Number
Unit of Measure: Percent of participants
27.4 28.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HIVpos/INH, HIVpos/PL
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments Threshold p-value for significance = 0.0492
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.67 to 1.44
Estimation Comments Hazard ratio for INH relative to Placebo
2.Primary Outcome
Title Time From Randomization to Development of TB Infection or Death Among Perinatally Exposed, HIV-uninfected Children
Hide Description Criteria for diagnosis with TB infection were outlined in the protocol. TB infection included TB disease (see primary outcome measure 1 for definition) and latent TB infection. Latent TB infection was diagnosed by a positive tuberculin skin test (TST) based on a purified protein derivative (PPD) performed at week 96. Participant records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB infection. Results report percent of participants reaching TB infection or death by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
HIVneg who started study treatment were included. Time from randomization to first of TB infection/death was calculated. Participants lost-to-follow-up before 96 wks were censored at the time of loss-to-follow-up. Participants in follow-up at 96 weeks (+12 week window) who were free of TB infection were censored at 96 weeks (+12 week window).
Arm/Group Title HIVneg/INH HIVneg/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 403 401
Measure Type: Number
Unit of Measure: Percent of participants
10.9 12.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HIVneg/INH, HIVneg/PL
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments Threshold p-value for significance = 0.0493
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.55 to 1.30
Estimation Comments Hazard ratio for INH relative to Placebo
3.Secondary Outcome
Title Time From Randomization to Development of TB Infection or Death Among HIV-infected Children
Hide Description Criteria for diagnosis with TB infection were outlined in the protocol. TB infection included TB disease (see primary outcome measure 1 for definition) and latent TB infection. Latent TB infection was diagnosed by a positive TST based on a PPD performed at week 96. Participant records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB infection. Results report percent of participants reaching TB infection or death by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
HIVpos starting study treatment were included. Time from randomization to first of TB infection/death was calculated. Participants LTF <96 weeks (+12 wk) censored at the time LTF. Participants in follow-up at 96 wks free of TB infection censored at 96 wks. Participants on study when study discontinued were censored at discontinuation visit.
Arm/Group Title HIVpos/INH HIVpos/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 273 274
Measure Type: Number
Unit of Measure: Percent of participants
29.4 32.8
4.Secondary Outcome
Title Time From Randomization to HIV Disease Progression or Death Among HIV-infected Children
Hide Description HIV disease progression was defined as any advancement in Centers for Disease Control (CDC) disease category from entry or death. If a participant was CDC disease category C at entry progression was defined as death. Results report percent of participants with HIV progression or death by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes HIVpos starting study treatment. Time from randomization to first of disease progression/death calculated. Censored if LTF <96 wks, at 96 wks (if on study) or at discontinuation visit. Participants found to be HIVneg upon repeat testing could only progress by meeting a death endpoint.
Arm/Group Title HIVpos/INH HIVpos/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 273 274
Measure Type: Number
Unit of Measure: Percent of participants
30.6 22.5
5.Secondary Outcome
Title Time From Randomization to Development of TB Disease or Death Among Perinatally Exposed, HIV-uninfected Children
Hide Description Criteria for diagnosis with TB disease were: Definite-isolation of M.tb or positive stain on CSF; Probable-positive AFB stain on fluids/tissues other than CSF and sufficient clinical criteria/radiographic evidence suggestive of TB; Possible-abnormal chest radiograph suggestive of PTB and either a +ve TST or minimum score on algorithm to diagnose clinical TB. All records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB disease. Results report percent of participants reaching TB disease/death by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes HIVneg who started study treatment. Time from randomization to the first of TB disease/death was calculated. Participants lost-to-follow-up before 96 weeks (+12 week window)were censored at the time of loss-to-follow-up. Participants in follow-up at 96 weeks who were free of TB disease were censored at 96 weeks (+12 week window).
Arm/Group Title HIVneg/INH HIVneg/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 403 401
Measure Type: Number
Unit of Measure: Percent of participants
8.3 9.1
6.Secondary Outcome
Title Time From Randomization to Development of TB Disease Among HIV Infected and Perinatally Exposed, HIV-uninfected Children
Hide Description Criteria for diagnosis with TB disease were: Definite-isolation of M.tb or positive stain on CSF; Probable-positive AFB stain on fluids/tissues other than CSF and sufficient clinical criteria/radiographic evidence suggestive of TB; Possible-abnormal chest radiograph suggestive of PTB and either a +ve TST or minimum score on algorithm to diagnose clinical TB. All records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB disease. Results report percent of participants reaching TB disease/death by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes all starting study treatment. Time from randomization to development of TB disease was calculated. Participants LTF <96 wks (+12 wks) censored at time of LTF. Participants in follow-up at 96 wks free of TB disease censored at 96 wks. HIVpos on study when study discontinued were censored at their discontinuation visit.
Arm/Group Title HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 403 401 273 274
Measure Type: Number
Unit of Measure: Percent of participants
7.8 8.5 20.3 23.7
7.Secondary Outcome
Title Time From Randomization to Development of TB Infection Among HIV-infected and Perinatally Exposed, HIV-uninfected Children
Hide Description Criteria for diagnosis with TB infection were outlined in the protocol. TB infection included TB disease (see primary outcome measure 1 for definition) and latent TB infection. Latent TB infection was diagnosed by a positive TST based on a PPD performed at week 96. Participant records were reviewed by an Endpoint Review Group to verify that participants had met the criteria for TB infection. Results report percent of participants reaching TB infection by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes all starting study treatment. Time from randomization to development of TB infection was calculated. Participants LTF <96 weeks (+12 wks) censored at the time of LTF. Participants in follow-up at 96 wks free of TB infection were censored at 96 wks. HIVpos on study when study discontinued censored at their discontinuation visit.
Arm/Group Title HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 403 401 273 274
Measure Type: Number
Unit of Measure: Percent of participants
10.4 12.1 22.4 27.9
8.Secondary Outcome
Title Time From Randomization to Death Among HIV-infected and Perinatally Exposed, HIV-uninfected Children
Hide Description Deaths from any cause were included. Results report percent of participants dying by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes all starting study treatment. Time from randomization to death was calculated. Participants LTF <96 weeks (+12 wks) censored at the time of LTF. Participants in follow-up at 96 wks (+12 wks) censored at 96 weeks. HIVpos on study when study was discontinued were censored at their discontinuation visit.
Arm/Group Title HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 403 401 273 274
Measure Type: Number
Unit of Measure: Percent of participants
0.8 0.8 11.6 7.2
9.Secondary Outcome
Title Time From Randomization to First New Grade 3 or Worse Adverse Event Among HIV-infected and Perinatally Exposed, HIV-uninfected Children
Hide Description Signs, symptoms and laboratory values were graded according to the Division of AIDS Adverse Event Grading System. Any event of grade 3 or higher not present at entry that occurred after randomization was classified as a new event. Results report percent of participants with a new event by week 96 calculated using the Kaplan-Meier method.
Time Frame Through to week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes all starting treatment. Time from randomization to first new adverse event (AE) calculated. For lab toxicities, censored at visit following permanent discontinuation of study drugs. For signs/symptoms, participants in follow-up at 96 wks (+12) with no new grade >=3 AE censored at 96 wks. Participants LTF <96 wks censored at LTF.
Arm/Group Title HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 403 401 273 274
Measure Type: Number
Unit of Measure: Percent of participants
New >=grade 3 sign/symptom 5.0 4.2 16.8 11.7
New >= grade 3 peripheral neuropathy 1.1 0.3 2.4 0.8
New >=grade 3 lab abnormality 4.9 4.6 11.3 10.1
New >=grade 3 hemoglobin 0.0 0.0 1.8 1.2
New >=grade 3 ANC 1.7 0.3 1.6 3.5
New >=grade 3 platelets 0.3 0.0 1.7 0.9
New >=grade 3 SGOT 1.0 2.8 0.4 2.5
New >=grade 3 SGPT 2.8 4.4 5.9 4.0
Time Frame From study enrollment until study completion and before May 25, 2009 (primary completion date)
Adverse Event Reporting Description 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 >=grade 3 AEs defined by the "DAIDS Table for Grading the Severity of Adult and Pediatric AEs", V1.0, 12/2004.
 
Arm/Group Title HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Hide Arm/Group Description Perinatally exposed, HIV-uninfected (HIVneg) children receiving Isoniazid (INH)10-20 mg/kg orally once a day for 96 weeks + Trimethoprim/Sulfamethoxazole (TMP/SMX) 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding Perinatally-exposed, HIV-uninfected (HIVneg) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until HIV status is confirmed and child is no longer at risk of acquiring HIV through breastfeeding HIV-infected (HIVpos) children receiving Isoniazid (INH) 10-20 mg/kg orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines. HIV-infected (HIVpos) children receiving Isoniazid placebo (PL) orally once a day for 96 weeks + TMP/SMX 5 mg/kg of TMP component orally once a day until one year of age. TMP/SMX may have been continued after one year of age according to WHO guidelines.
All-Cause Mortality
HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/403 (6.20%)   18/401 (4.49%)   55/273 (20.15%)   42/274 (15.33%) 
Blood and lymphatic system disorders         
Anaemia  1  0/403 (0.00%)  0/401 (0.00%)  2/273 (0.73%)  1/274 (0.36%) 
Neutropenia  1  1/403 (0.25%)  0/401 (0.00%)  5/273 (1.83%)  1/274 (0.36%) 
Pancytopenia  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
Thrombocytopenia  1  0/403 (0.00%)  0/401 (0.00%)  2/273 (0.73%)  0/274 (0.00%) 
Cardiac disorders         
Cardiac failure  1  1/403 (0.25%)  0/401 (0.00%)  0/273 (0.00%)  0/274 (0.00%) 
Eye disorders         
Visual acuity reduced  1  1/403 (0.25%)  0/401 (0.00%)  0/273 (0.00%)  0/274 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
General disorders         
Accidental death  1  1/403 (0.25%)  0/401 (0.00%)  0/273 (0.00%)  0/274 (0.00%) 
Death  1  1/403 (0.25%)  2/401 (0.50%)  8/273 (2.93%)  6/274 (2.19%) 
Sudden infant death syndrome  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Hepatobiliary disorders         
Hepatic failure  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
Hepatotoxicity  1  6/403 (1.49%)  5/401 (1.25%)  6/273 (2.20%)  6/274 (2.19%) 
Infections and infestations         
Bronchiolitis  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Bronchopneumonia  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Encephalitis viral  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Escherichia sepsis  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Gastroenteritis  1  0/403 (0.00%)  1/401 (0.25%)  9/273 (3.30%)  6/274 (2.19%) 
HIV infection  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Infection  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Lobar pneumonia  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Pneumonia  1  0/403 (0.00%)  0/401 (0.00%)  6/273 (2.20%)  5/274 (1.82%) 
Pneumonia cytomegaloviral  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Pneumonia herpes viral  1  0/403 (0.00%)  1/401 (0.25%)  0/273 (0.00%)  0/274 (0.00%) 
Pneumonia necrotising  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
Sepsis  1  0/403 (0.00%)  0/401 (0.00%)  2/273 (0.73%)  1/274 (0.36%) 
Tuberculosis  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Tuberculosis of eye  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
Injury, poisoning and procedural complications         
Drug toxicity  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
Poisoning  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
Investigations         
Alanine aminotransferase increased  1  0/403 (0.00%)  1/401 (0.25%)  4/273 (1.47%)  2/274 (0.73%) 
Aspartate aminotransferase increased  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  3/274 (1.09%) 
Haemoglobin decreased  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
Liver function test abnormal  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Neutrophil count decreased  1  5/403 (1.24%)  6/401 (1.50%)  2/273 (0.73%)  2/274 (0.73%) 
Transaminases increased  1  2/403 (0.50%)  1/401 (0.25%)  2/273 (0.73%)  2/274 (0.73%) 
Metabolism and nutrition disorders         
Failure to thrive  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Nervous system disorders         
Encephalopathy  1  1/403 (0.25%)  0/401 (0.00%)  0/273 (0.00%)  0/274 (0.00%) 
Neuropathy peripheral  1  5/403 (1.24%)  1/401 (0.25%)  1/273 (0.37%)  0/274 (0.00%) 
Status epilepticus  1  1/403 (0.25%)  0/401 (0.00%)  0/273 (0.00%)  0/274 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Aspiration  1  0/403 (0.00%)  0/401 (0.00%)  1/273 (0.37%)  0/274 (0.00%) 
Skin and subcutaneous tissue disorders         
Erythema multiforme  1  0/403 (0.00%)  0/401 (0.00%)  0/273 (0.00%)  1/274 (0.36%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
HIVneg/INH HIVneg/PL HIVpos/INH HIVpos/PL
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   353/403 (87.59%)   368/401 (91.77%)   264/273 (96.70%)   268/274 (97.81%) 
Blood and lymphatic system disorders         
Lymphadenitis  1  0/403 (0.00%)  1/401 (0.25%)  10/273 (3.66%)  28/274 (10.22%) 
Gastrointestinal disorders         
Diarrhoea  1  16/403 (3.97%)  28/401 (6.98%)  18/273 (6.59%)  26/274 (9.49%) 
Infections and infestations         
AIDS encephalopathy  1  0/403 (0.00%)  1/401 (0.25%)  21/273 (7.69%)  24/274 (8.76%) 
Acarodermatitis  1  22/403 (5.46%)  20/401 (4.99%)  9/273 (3.30%)  15/274 (5.47%) 
Bronchiolitis  1  40/403 (9.93%)  41/401 (10.22%)  12/273 (4.40%)  12/274 (4.38%) 
Bronchitis  1  24/403 (5.96%)  33/401 (8.23%)  18/273 (6.59%)  11/274 (4.01%) 
Gastroenteritis  1  90/403 (22.33%)  104/401 (25.94%)  81/273 (29.67%)  79/274 (28.83%) 
Oral candidiasis  1  13/403 (3.23%)  11/401 (2.74%)  54/273 (19.78%)  54/274 (19.71%) 
Otitis media acute  1  140/403 (34.74%)  162/401 (40.40%)  46/273 (16.85%)  53/274 (19.34%) 
Pharyngitis  1  122/403 (30.27%)  131/401 (32.67%)  68/273 (24.91%)  63/274 (22.99%) 
Pneumonia  1  11/403 (2.73%)  12/401 (2.99%)  33/273 (12.09%)  28/274 (10.22%) 
Pulmonary tuberculosis  1  39/403 (9.68%)  44/401 (10.97%)  47/273 (17.22%)  47/274 (17.15%) 
Tonsilitis  1  99/403 (24.57%)  108/401 (26.93%)  41/273 (15.02%)  41/274 (14.96%) 
Upper respiratory tract infection  1  26/403 (6.45%)  36/401 (8.98%)  5/273 (1.83%)  4/274 (1.46%) 
Investigations         
Alanine aminotransferase increased  1  124/403 (30.77%)  121/401 (30.17%)  130/273 (47.62%)  114/274 (41.61%) 
Aspartate aminotransferase increased  1  88/403 (21.84%)  94/401 (23.44%)  109/273 (39.93%)  86/274 (31.39%) 
Gamma-glutamyltransferase increased  1  9/403 (2.23%)  8/401 (2.00%)  14/273 (5.13%)  7/274 (2.55%) 
Haemoglobin decreased  1  70/403 (17.37%)  72/401 (17.96%)  176/273 (64.47%)  176/274 (64.23%) 
Neutrophil count decreased  1  117/403 (29.03%)  100/401 (24.94%)  100/273 (36.63%)  105/274 (38.32%) 
Metabolism and nutrition disorders         
Failure to thrive  1  51/403 (12.66%)  33/401 (8.23%)  41/273 (15.02%)  42/274 (15.33%) 
Nervous system disorders         
Neuropathy peripheral  1  47/403 (11.66%)  50/401 (12.47%)  75/273 (27.47%)  87/274 (31.75%) 
Skin and subcutaneous tissue disorders         
Eczema  1  41/403 (10.17%)  41/401 (10.22%)  65/273 (23.81%)  49/274 (17.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
DSMB recommended stopping study due to futility: "no compelling reason to enroll additional infants" or "to continue to treat participants with the blinded study medication". Week 192 analyses not done as <4% (26%) of HIVpos (HIVneg) reached wk 192
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 Trial 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
Responsible Party: Wende Levy, IMPAACT
ClinicalTrials.gov Identifier: NCT00080119     History of Changes
Other Study ID Numbers: PACTG P1041
U01AI068632 ( U.S. NIH Grant/Contract )
First Submitted: March 23, 2004
First Posted: March 25, 2004
Results First Submitted: July 1, 2010
Results First Posted: October 19, 2010
Last Update Posted: February 14, 2011