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Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in Persons With HIV

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ClinicalTrials.gov Identifier: NCT01601626
Recruitment Status : Terminated (The study was stopped early due to feasibility concerns.)
First Posted : May 18, 2012
Results First Posted : February 13, 2018
Last Update Posted : February 13, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HIV Infection
Tuberculosis
Interventions Drug: Standard-dose Lopinavir/Ritonavir
Drug: Double-dose Lopinavir/Ritonavir
Drug: Raltegravir
Drug: Isoniazid
Drug: Pyridoxine
Drug: Pyrazinamide
Drug: Ethambutol
Drug: Rifabutin
Drug: Rifampin
Enrollment 71
Recruitment Details Study participants were recruited at 9 sites from 5 countries (2 each from Brazil, Haiti, Peru, and South Africa and 1 from Kenya) between July 2013 and February 2016.
Pre-assignment Details  
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Period Title: Overall Study
Started 24 24 23
Completed 21 19 21
Not Completed 3 5 2
Reason Not Completed
Death             1             1             1
Lost to Follow-up             1             2             0
Unable to Get to Clinic             0             1             0
Withdrawal by Subject             0             1             1
Not Willing to Adhere to Requirements             1             0             0
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT Total
Hide Arm/Group Description

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Total of all reporting groups
Overall Number of Baseline Participants 24 24 23 71
Hide Baseline Analysis Population Description
All randomized participants were included.
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 24 participants 24 participants 23 participants 71 participants
42
(33 to 49)
35
(29 to 41)
38
(32 to 47)
37
(32 to 46)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 23 participants 71 participants
Female
13
  54.2%
9
  37.5%
15
  65.2%
37
  52.1%
Male
11
  45.8%
15
  62.5%
8
  34.8%
34
  47.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 23 participants 71 participants
Black of African Origin
7
  29.2%
8
  33.3%
6
  26.1%
21
  29.6%
Black African
8
  33.3%
6
  25.0%
4
  17.4%
18
  25.4%
White
4
  16.7%
2
   8.3%
6
  26.1%
12
  16.9%
Mixed Black
3
  12.5%
5
  20.8%
3
  13.0%
11
  15.5%
Mestizo
2
   8.3%
2
   8.3%
2
   8.7%
6
   8.5%
Mixed, of Predominantly African Ancestry
0
   0.0%
0
   0.0%
1
   4.3%
1
   1.4%
Other
0
   0.0%
1
   4.2%
1
   4.3%
2
   2.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Haiti Number Analyzed 24 participants 24 participants 23 participants 71 participants
6 6 6 18
Brazil Number Analyzed 24 participants 24 participants 23 participants 71 participants
8 10 10 28
South Africa Number Analyzed 24 participants 24 participants 23 participants 71 participants
4 3 3 10
Kenya Number Analyzed 24 participants 24 participants 23 participants 71 participants
4 3 2 9
Peru Number Analyzed 24 participants 24 participants 23 participants 71 participants
2 2 2 6
Qualitative HIV RNA   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 23 participants 71 participants
Less than 40 copies/mL
4
  16.7%
2
   8.3%
3
  13.0%
9
  12.7%
Greater than or equal to 40 copies/mL
20
  83.3%
22
  91.7%
20
  87.0%
62
  87.3%
[1]
Measure Description: The lower limit of quantification of the HIV RNA assay used in the protocol was 40 copies/mL.
Quantitative HIV RNA   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 20 participants 22 participants 20 participants 62 participants
4.7
(3.4 to 5.6)
4.8
(4.2 to 5.3)
4.2
(3.2 to 5.0)
4.6
(3.5 to 5.3)
[1]
Measure Description: The lower limit of quantification of the HIV RNA assay used in the protocol was 40 copies/mL.
[2]
Measure Analysis Population Description: Quantitative HIV RNA was summarized in the participants whose HIV RNA was above the assay's lower limit of quantification.
CD4 Cell Count  
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^3
Number Analyzed 24 participants 24 participants 23 participants 71 participants
128
(60 to 234)
117
(51 to 246)
158
(73 to 202)
130
(55 to 231)
Tuberculosis (TB) Diagnosis Certainty   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 23 participants 71 participants
Confirmed Pulmonary TB
13
  54.2%
8
  33.3%
6
  26.1%
27
  38.0%
Confirmed Extrapulmonary TB
1
   4.2%
1
   4.2%
3
  13.0%
5
   7.0%
Confirmed Pulmonary and Extrapulmonary TB
1
   4.2%
0
   0.0%
0
   0.0%
1
   1.4%
Probable Pulmonary TB
9
  37.5%
15
  62.5%
13
  56.5%
37
  52.1%
Probable Extrapulmonary TB
0
   0.0%
0
   0.0%
1
   4.3%
1
   1.4%
[1]
Measure Description: The protocol document contains the definitions of confirmed and probable for pulmonary and extrapulmonary TB in section 4.1.3.
Acid Fast Bacilli (AFB) Smear  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 23 participants 71 participants
Positive
11
  45.8%
8
  33.3%
6
  26.1%
25
  35.2%
Negative
10
  41.7%
14
  58.3%
16
  69.6%
40
  56.3%
No Results Available
3
  12.5%
2
   8.3%
1
   4.3%
6
   8.5%
Mycobacteria Tuberculosis (MTB) Culture  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 23 participants 71 participants
MTB-Positive
13
  54.2%
8
  33.3%
9
  39.1%
30
  42.3%
MTB-Negative
6
  25.0%
13
  54.2%
13
  56.5%
32
  45.1%
No Results Available
5
  20.8%
3
  12.5%
1
   4.3%
9
  12.7%
Body Mass Index (BMI)  
Median (Inter-Quartile Range)
Unit of measure:  Kg/m^2
Number Analyzed 24 participants 24 participants 23 participants 71 participants
19.9
(18.3 to 22.1)
20.4
(17.9 to 21.5)
18.9
(17.9 to 21.5)
19.6
(17.9 to 21.5)
1.Primary Outcome
Title Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48.
Hide Description The percent of participants whose HIV viral load was less than 400 copies/mL at week 48 was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. Participants who were lost-to-follow-up or dead by week 48 or had missing results at week 48 were coded as having HIV viral load greater than 400 copies/mL. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
58.3
(38.8 to 75.5)
66.7
(46.7 to 82.0)
60.9
(40.8 to 77.8)
2.Secondary Outcome
Title Percent of Participants Who Experienced Sputum Conversion at Week 8.
Hide Description Sputum conversion was defined as culture MTB-negative at week 8 or AFB smear negative at week 8 (and culture contaminated or missing at week 8); there were no Xpert MTB/RIF results at week 8. The percent of participants experienced sputum conversion at week 8 was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were either culture MTB-positive at entry; AFB smear positive at entry (and culture MTB-negative, contaminated, or missing at entry); or Xpert MTB/RIF positive at entry (and culture or smear negative, contaminated, or missing at entry) were included in the analysis.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 16 11 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
87.5
(64.0 to 96.5)
81.8
(52.3 to 94.9)
70.0
(39.7 to 89.2)
3.Secondary Outcome
Title Percent of Participants Who Experienced TB Treatment Failure
Hide Description TB treatment failure was defined as having a MTB-positive culture after 16 weeks of TB treatment for a participant who was documented to be taking TB medications. The percent of participants who experienced TB treatment failure was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After 16 weeks and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 13.8)
0.0
(0.0 to 13.8)
0.0
(0.0 to 14.3)
4.Secondary Outcome
Title Percent of Participants Who Experienced TB Relapse/Recurrence
Hide Description TB relapse/recurrence was defined as having had 2 consecutive MTB-negative cultures and subsequently had clinical or radiographic deterioration consistent with active TB at or after week 24 and before week 72. The percent of participants who experienced TB relapse/recurrence was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame At or after 24 weeks and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 13.8)
4.2
(0.7 to 20.2)
4.3
(0.8 to 21.0)
5.Secondary Outcome
Title Percent of Participants Who Experienced TB Relapse/Recurrence and Who Had TB Drug Resistance
Hide Description TB relapse/recurrence was defined as having had 2 consecutive MTB-negative cultures and subsequently had clinical or radiographic deterioration consistent with active TB at or after week 24 and before week 72. The drug resistance was determined based on phenotypic methods. The percent of participants who experienced TB relapse/recurrence and who had TB drug resistance was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame At or after 24 weeks and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who experienced TB relapse/recurrence were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 0 1 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
0
(0.0 to 79.3)
0
(0.0 to 32.4)
6.Secondary Outcome
Title Percent of Participants Whose HIV Viral Load Was Less Than 50 Copies/mL at Week 48
Hide Description The percent of participants whose HIV viral load was less than 50 copies/mL at week 48 was calculated with an associated standard error. Participants who were lost-to-follow-up or dead by week 48 or had missing RNA at week 48 were coded as having HIV viral load greater than 50 copies/mL. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
45.8
(27.9 to 64.9)
54.2
(35.1 to 72.1)
56.5
(36.8 to 74.4)
7.Secondary Outcome
Title Number of Participants Reporting a Grade 3 or 4 Sign or Symptom
Hide Description The number of participants reporting a grade 3 (severe) or grade 4 (life-threatening) sign or symptom were summarized. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After randomization and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Count of Participants
Unit of Measure: Participants
7
  29.2%
5
  20.8%
5
  21.7%
8.Secondary Outcome
Title Number of Participants Reporting a Grade 3 or 4 Laboratory Abnormality
Hide Description The number of participants reporting a grade 3 (severe) or grade 4 (life-threatening) laboratory abnormality were summarized. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After randomization and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Count of Participants
Unit of Measure: Participants
6
  25.0%
3
  12.5%
5
  21.7%
9.Secondary Outcome
Title Percent of Participants Who Interrupted or Discontinued at Least One HIV Drug Due to Toxicity
Hide Description The percent of participants who interrupted or discontinued at least one HIV drug due to toxicity was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After randomization and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.8
(9.2 to 40.5)
16.7
(6.7 to 35.9)
21.7
(9.7 to 41.9)
10.Secondary Outcome
Title Percent of Participants Who Interrupted or Discontinued at Least One TB Drug Due to Toxicity
Hide Description The percent of participants who interrupted or discontinued at least one TB drug due to toxicity was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After randomization and through to the discontinuation of the last TB drug
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.8
(9.2 to 40.5)
8.3
(2.3 to 25.8)
13.0
(4.5 to 32.1)
11.Secondary Outcome
Title Percent of Participants Who Experienced HIV Virologic Failure
Hide Description Virologic failure was defined as the occurrence of two consecutive plasma HIV-1 RNA levels ≥1000 copies/mL at or after 16 weeks and within 24 weeks of treatment initiation or ≥400 copies/mL at or after 24 weeks of treatment, regardless of whether randomized ART was being taken at the time of virologic failure. Participants who were missing data due to being lost-to-follow-up or dead were coded as virologic failures. The percent of participants who experienced HIV virologic failure was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame At weeks 16, 24, 48, and 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
29.2
(14.9 to 49.2)
50.0
(31.4 to 68.6)
30.4
(15.6 to 50.9)
12.Secondary Outcome
Title Cumulative Probability of HIV Virologic Failure at Week 72
Hide Description Virologic failure was defined as the occurrence of two consecutive plasma HIV-1 RNA levels ≥1000 copies/mL at or after 16 weeks and within 24 weeks of treatment initiation or ≥400 copies/mL at or after 24 weeks of treatment, regardless of whether randomized ART was being taken at the time of virologic failure. The percent of participants with HIV virologic failure at week 72 was calculated using a Kaplan-Meier estimator with an associated standard error. The confidence interval was calculated using a log-log transformation. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame At weeks 16, 24, 48, and 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: cumulative events per 100 participants
29.2
(15.1 to 51.6)
50.0
(32.2 to 70.9)
30.4
(15.8 to 53.4)
13.Secondary Outcome
Title Number of Participants Who Experienced MTB IRIS
Hide Description The number of participants who experienced MTB immune reconstitution inflammatory syndrome (IRIS) was summarized. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After randomization and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Count of Participants
Unit of Measure: Participants
1
   4.2%
2
   8.3%
3
  13.0%
14.Secondary Outcome
Title CD4 Count Change From Baseline to Week 8
Hide Description The difference in CD4 count from baseline to week 8 was calculated as the CD4 count at week 8 minus the CD4 count at baseline. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame Baseline and 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had CD4 cell count data available at baseline and week 8 were included in the analysis.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 22 24 22
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^3
7
(-71 to 33)
26
(2 to 106)
37
(-60 to 79)
15.Secondary Outcome
Title CD4 Count Change From Baseline to Week 24
Hide Description The difference in CD4 count from baseline to week 24 was calculated as the CD4 count at week 24 minus the CD4 count at baseline. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had CD4 cell count data available at baseline and week 24 were included in the analysis.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 21 23 18
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^3
20
(-38 to 56)
56
(12 to 110)
13
(-64 to 100)
16.Secondary Outcome
Title CD4 Count Change From Baseline to Week 48
Hide Description The difference in CD4 count from baseline to week 48 was calculated as the CD4 count at week 48 minus the CD4 count at baseline. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame Baseline and 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had CD4 cell count data available at baseline and week 48 were included in the analysis.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 20 20 18
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^3
99
(1 to 159)
119
(57 to 263)
74
(16 to 115)
17.Secondary Outcome
Title CD4 Count Change From Baseline to Week 72
Hide Description The difference in CD4 count from baseline to week 72 was calculated as the CD4 count at week 72 minus the CD4 count at baseline. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame Baseline and 72 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had CD4 cell count data available at baseline and week 72 were included in the analysis.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 20 19 20
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^3
126
(26 to 247)
212
(93 to 281)
54
(-6 to 203)
18.Secondary Outcome
Title Percent of Participants Who Experienced a New AIDS-defining Illness
Hide Description New post-randomization diagnoses were considered AIDS-defining based on the CDC classification system. The percent of participants who experienced a new AIDS-defining illness was calculated with an associated standard error. The confidence interval was calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After randomization and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 13.8)
4.2
(0.7 to 20.2)
0.0
(0.0 to 14.3)
19.Secondary Outcome
Title Percent of Participants Who Died
Hide Description The percent of participants who died was calculated with an associated standard error. Confidence intervals were calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After randomization and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.2
(0.7 to 20.2)
4.7
(0.7 to 20.2)
4.3
(0.8 to 21.0)
20.Secondary Outcome
Title Percent of Participants Who Experienced a New AIDS-defining Illness or Died
Hide Description New post-randomization diagnoses were considered AIDS-defining based on the CDC classification system. The percent of participants who experienced a new AIDS-defining illness or died was calculated with an associated standard error. Confidence intervals were calculated using Wilson's score method. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame After randomization and through week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included.
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 24 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.2
(0.7 to 20.2)
8.3
(2.3 to 25.8)
4.3
(0.8 to 21.0)
21.Other Pre-specified Outcome
Title LPV Cmax and Cmin in Participants Enrolled in Arms A, B, and C
Hide Description Describe LPV plasma pharmacokinetic (PK) characteristics (maximum concentration [Cmax] and minimum concentration [Cmin]) in participants enrolled in Arms A, B, and C, determined by non-compartmental analysis of 12-hour PK sampling. The pre-dose concentration was determined using a sample drawn 12 hours after the previous LPV dose and was used as the 12-hour LPV concentration. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame At 2 weeks: pre-dose and at 2, 4, 5, and 6 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were included in this analysis if they completed the PK visit, did not miss any doses of any study-required medications on the day prior to the PK visit, and the LPV concentration at the pre-dose draw was above the assay's lower limit of quantification (20 ng/mL).
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 19 17 14
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
Maximum Concentration (Cmax)
18531
(12978 to 21627)
18138
(11366 to 22807)
16802
(12609 to 24924)
Minimum Concentration (Cmin)
9920
(2421 to 16127)
8033
(4061 to 9481)
8548
(5603 to 15968)
22.Other Pre-specified Outcome
Title LPV AUC in Participants Enrolled in Arms A, B, and C
Hide Description Describe LPV plasma PK characteristics (area under the curve [AUC] between 0 and 12 hours) in participants enrolled in Arms A, B, and C, determined by non-compartmental analysis of 12-hour PK sampling. The pre-dose concentration was determined using a sample drawn 12 hours after the previous LPV dose and was used as the 12-hour LPV concentration. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame At 2 weeks: pre-dose and at 2, 4, 5, and 6 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were included in this analysis if they completed the PK visit, did not miss any doses of any study-required medications on the day prior to the PK visit, and the LPV concentration at the pre-dose draw was above the assay's lower limit of quantification (20 ng/mL).
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 19 17 14
Median (Inter-Quartile Range)
Unit of Measure: hours*ng/mL
159796
(113493 to 222251)
161772
(102118 to 209509)
149247
(122324 to 243273)
23.Other Pre-specified Outcome
Title RBT Cmax and Cmin in Participants Enrolled in Arms A and C
Hide Description Describe RBT plasma PK characteristics (Cmax and Cmin) in participants enrolled in Arms A and C, determined by non-compartmental analysis of 24-hour PK sampling. The pre-dose concentration was determined using a sample drawn 24 hours after the previous RBT dose. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were included in this analysis if they completed the PK visit, did not miss any doses of any study-required medications on the day prior to the PK visit, followed the protocol-required RBT dosing schedule, and the RBT concentration at the pre-dose draw was above the assay's lower limit of quantification (75 ng/mL).
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 18 0 11
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
Maximum Concentration (Cmax)
461
(361 to 625)
349
(249 to 505)
Minimum Concentration (Cmin)
161
(104 to 255)
115
(88 to 171)
24.Other Pre-specified Outcome
Title RBT AUC in Participants Enrolled in Arms A and C
Hide Description Describe RBT plasma PK characteristics (area under the curve [AUC] between 0 and 24 hours) in participants enrolled in Arms A and C, determined by non-compartmental analysis of 24-hour PK sampling. The pre-dose concentration was determined using a sample drawn 24 hours after the previous RBT dose. As stated in the Detailed Study Description of the Protocol Section, formal statistical comparisons were not undertaken because of limited sample size.
Time Frame At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were included in this analysis if they completed the PK visit, did not miss any doses of any study-required medications on the day prior to the PK visit, followed the protocol-required RBT dosing schedule, and the RBT concentration at the pre-dose draw was above the assay's lower limit of quantification (75 ng/mL).
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 18 0 11
Median (Inter-Quartile Range)
Unit of Measure: hours*ng/mL
7374
(5909 to 11785)
5516
(4147 to 7060)
25.Other Pre-specified Outcome
Title RAL Cmax and Cmin in Participants Enrolled in Arm C
Hide Description Describe RAL plasma PK characteristics (Cmax and Cmin) in participants enrolled in Arm C, determined by non-compartmental analysis of 24-hour PK sampling. The pre-dose concentration was determined using a sample drawn 12 hours after the previous RAL dose and was used as the 12-hour RAL concentration.
Time Frame At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were included in this analysis if they completed the PK visit, did not miss any doses of any study-required medications on the day prior to the PK visit, and the RAL concentration at the pre-dose draw was above the assay's lower limit of quantification (5 ng/mL).
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 0 0 16
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
Maximum Concentration (Cmax)
2830
(469 to 4560)
Minimum Concentration (Cmin)
166
(53 to 197)
26.Other Pre-specified Outcome
Title RAL AUC in Participants Enrolled in Arm C
Hide Description Describe RAL plasma PK characteristics (area under the curve [AUC] between 0 and 24 hours) in participants enrolled in Arm C, determined by non-compartmental analysis of 24-hour PK sampling. The pre-dose concentration was determined using a sample drawn 12 hours after the previous RAL dose and was used as the 12-hour RAL concentration.
Time Frame At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were included in this analysis if they completed the PK visit, did not miss any doses of any study-required medications on the day prior to the PK visit, and the RAL concentration at the pre-dose draw was above the assay's lower limit of quantification (5 ng/mL).
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description:

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Overall Number of Participants Analyzed 0 0 16
Median (Inter-Quartile Range)
Unit of Measure: hours*ng/mL
11338
(2618 to 15363)
Time Frame From study entry to either premature study discontinuation or study completion at Week 72.
Adverse Event Reporting Description The study protocol required reporting of all new diagnoses; all new Grade 2 (moderate) or higher TB-related signs and symptoms, all new signs and symptoms Grade 3 (severe) or higher; all new all Grade 3 or higher laboratory values; and all signs, symptoms, and laboratory values that led to a change in treatment, regardless of grade. The DAIDS AE Grading Table (V1.0) and EAE Manual (V2.0) were used. All randomized participants who initiated study treatment were included.
 
Arm/Group Title A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Hide Arm/Group Description

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

All-Cause Mortality
A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/24 (4.17%)   1/24 (4.17%)   1/23 (4.35%) 
Show Serious Adverse Events Hide Serious Adverse Events
A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/24 (16.67%)   5/24 (20.83%)   5/23 (21.74%) 
Blood and lymphatic system disorders       
Anaemia  1  1/24 (4.17%)  1/24 (4.17%)  0/23 (0.00%) 
Pancytopenia  1  0/24 (0.00%)  0/24 (0.00%)  1/23 (4.35%) 
Thrombocytopenia  1  0/24 (0.00%)  1/24 (4.17%)  0/23 (0.00%) 
Cardiac disorders       
Cardiac failure congestive  1  0/24 (0.00%)  0/24 (0.00%)  1/23 (4.35%) 
Eye disorders       
Iridocyclitis  1  1/24 (4.17%)  0/24 (0.00%)  0/23 (0.00%) 
Gastrointestinal disorders       
Abdominal pain upper  1  0/24 (0.00%)  0/24 (0.00%)  1/23 (4.35%) 
Gastrointestinal disorder  1  0/24 (0.00%)  1/24 (4.17%)  0/23 (0.00%) 
Infections and infestations       
Acute hepatitis B  1  1/24 (4.17%)  0/24 (0.00%)  0/23 (0.00%) 
Disseminated tuberculosis  1  1/24 (4.17%)  0/24 (0.00%)  0/23 (0.00%) 
Gastroenteritis  1  1/24 (4.17%)  1/24 (4.17%)  0/23 (0.00%) 
Pneumonia  1  0/24 (0.00%)  0/24 (0.00%)  1/23 (4.35%) 
Pneumonia bacterial  1  0/24 (0.00%)  1/24 (4.17%)  0/23 (0.00%) 
Rhodococcus infection  1  0/24 (0.00%)  1/24 (4.17%)  0/23 (0.00%) 
Sepsis  1  1/24 (4.17%)  0/24 (0.00%)  0/23 (0.00%) 
Tuberculosis gastrointestinal  1  0/24 (0.00%)  0/24 (0.00%)  1/23 (4.35%) 
Injury, poisoning and procedural complications       
Accidental overdose  1  0/24 (0.00%)  1/24 (4.17%)  0/23 (0.00%) 
Head injury  1  0/24 (0.00%)  1/24 (4.17%)  0/23 (0.00%) 
Metabolism and nutrition disorders       
Lactic acidosis  1  0/24 (0.00%)  0/24 (0.00%)  1/23 (4.35%) 
Nervous system disorders       
Seizure  1  1/24 (4.17%)  0/24 (0.00%)  0/23 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  1/24 (4.17%)  0/24 (0.00%)  0/23 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pneumothorax  1  0/24 (0.00%)  0/24 (0.00%)  1/23 (4.35%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
A: Standard-dose LPV/r w/RBT B: Double-dose LPV/r w/RIF C: Standard-Dose LPV/r + RAL w/RBT
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/24 (100.00%)   23/24 (95.83%)   23/23 (100.00%) 
Blood and lymphatic system disorders       
Anaemia  1  3/24 (12.50%)  1/24 (4.17%)  0/23 (0.00%) 
Lymphadenopathy  1  1/24 (4.17%)  2/24 (8.33%)  2/23 (8.70%) 
Cardiac disorders       
Tachycardia  1  1/24 (4.17%)  2/24 (8.33%)  3/23 (13.04%) 
Eye disorders       
Eye pain  1  3/24 (12.50%)  0/24 (0.00%)  0/23 (0.00%) 
Ocular hyperaemia  1  3/24 (12.50%)  0/24 (0.00%)  0/23 (0.00%) 
Uveitis  1  2/24 (8.33%)  0/24 (0.00%)  0/23 (0.00%) 
Visual acuity reduced  1  2/24 (8.33%)  0/24 (0.00%)  0/23 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  3/24 (12.50%)  1/24 (4.17%)  2/23 (8.70%) 
Dyspepsia  1  0/24 (0.00%)  0/24 (0.00%)  2/23 (8.70%) 
Dysphagia  1  1/24 (4.17%)  2/24 (8.33%)  0/23 (0.00%) 
Nausea  1  0/24 (0.00%)  1/24 (4.17%)  2/23 (8.70%) 
Oral disorder  1  3/24 (12.50%)  0/24 (0.00%)  2/23 (8.70%) 
Vomiting  1  2/24 (8.33%)  2/24 (8.33%)  2/23 (8.70%) 
General disorders       
Asthenia  1  2/24 (8.33%)  1/24 (4.17%)  1/23 (4.35%) 
Chest pain  1  2/24 (8.33%)  1/24 (4.17%)  1/23 (4.35%) 
Fatigue  1  2/24 (8.33%)  0/24 (0.00%)  2/23 (8.70%) 
Pyrexia  1  3/24 (12.50%)  6/24 (25.00%)  3/23 (13.04%) 
Infections and infestations       
Immune reconstitution inflammatory syndrome associated tuberculosis  1  1/24 (4.17%)  2/24 (8.33%)  4/23 (17.39%) 
Oral candidiasis  1  3/24 (12.50%)  3/24 (12.50%)  2/23 (8.70%) 
Pneumonia bacterial  1  2/24 (8.33%)  1/24 (4.17%)  1/23 (4.35%) 
Pulmonary tuberculosis  1  0/24 (0.00%)  2/24 (8.33%)  0/23 (0.00%) 
Purulent discharge  1  0/24 (0.00%)  2/24 (8.33%)  0/23 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  2/24 (8.33%)  3/24 (12.50%)  4/23 (17.39%) 
Aspartate aminotransferase increased  1  7/24 (29.17%)  7/24 (29.17%)  9/23 (39.13%) 
Blood albumin decreased  1  15/24 (62.50%)  15/24 (62.50%)  14/23 (60.87%) 
Blood alkaline phosphatase increased  1  6/24 (25.00%)  8/24 (33.33%)  6/23 (26.09%) 
Blood bicarbonate decreased  1  3/24 (12.50%)  2/24 (8.33%)  3/23 (13.04%) 
Blood bilirubin increased  1  2/24 (8.33%)  2/24 (8.33%)  1/23 (4.35%) 
Blood creatinine increased  1  3/24 (12.50%)  1/24 (4.17%)  1/23 (4.35%) 
Blood potassium decreased  1  0/24 (0.00%)  3/24 (12.50%)  1/23 (4.35%) 
Blood potassium increased  1  0/24 (0.00%)  1/24 (4.17%)  3/23 (13.04%) 
Blood sodium decreased  1  8/24 (33.33%)  8/24 (33.33%)  11/23 (47.83%) 
Blood sodium increased  1  3/24 (12.50%)  5/24 (20.83%)  4/23 (17.39%) 
Haemoglobin decreased  1  14/24 (58.33%)  9/24 (37.50%)  7/23 (30.43%) 
Neutrophil count decreased  1  3/24 (12.50%)  1/24 (4.17%)  3/23 (13.04%) 
Weight decreased  1  2/24 (8.33%)  3/24 (12.50%)  3/23 (13.04%) 
White blood cell count decreased  1  1/24 (4.17%)  1/24 (4.17%)  3/23 (13.04%) 
Metabolism and nutrition disorders       
Decreased appetite  1  2/24 (8.33%)  2/24 (8.33%)  1/23 (4.35%) 
Obesity  1  0/24 (0.00%)  0/24 (0.00%)  2/23 (8.70%) 
Musculoskeletal and connective tissue disorders       
Pain in extremity  1  2/24 (8.33%)  1/24 (4.17%)  0/23 (0.00%) 
Nervous system disorders       
Altered state of consciousness  1  2/24 (8.33%)  0/24 (0.00%)  0/23 (0.00%) 
Dizziness  1  2/24 (8.33%)  2/24 (8.33%)  1/23 (4.35%) 
Headache  1  2/24 (8.33%)  3/24 (12.50%)  0/23 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  2/24 (8.33%)  3/24 (12.50%)  1/23 (4.35%) 
Dyspnoea  1  1/24 (4.17%)  1/24 (4.17%)  3/23 (13.04%) 
Oropharyngeal plaque  1  1/24 (4.17%)  3/24 (12.50%)  0/23 (0.00%) 
Rales  1  0/24 (0.00%)  1/24 (4.17%)  3/23 (13.04%) 
Rhinorrhoea  1  0/24 (0.00%)  2/24 (8.33%)  0/23 (0.00%) 
Tachypnoea  1  0/24 (0.00%)  0/24 (0.00%)  2/23 (8.70%) 
Skin and subcutaneous tissue disorders       
Blister  1  1/24 (4.17%)  2/24 (8.33%)  1/23 (4.35%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
The study was terminated after 71 of 471 participants enrolled. Therefore, the study was under-powered and formal statistical comparisons between study arms were not undertaken as originally planned. Instead, summaries within study arm were provided.
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: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01601626     History of Changes
Other Study ID Numbers: ACTG A5290
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: May 16, 2012
First Posted: May 18, 2012
Results First Submitted: January 10, 2018
Results First Posted: February 13, 2018
Last Update Posted: February 13, 2018