Trial Outcomes & Findings for Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in Persons With HIV (NCT NCT01601626)

Last Updated: 2018-02-13

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

71 participants

Primary outcome timeframe

48 weeks

Results posted on

2018-02-13

Participant Flow

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.

Participant milestones

Participant milestones
Measure	A: Standard-dose LPV/r w/RBT 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.	B: Double-dose LPV/r w/RIF 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.	C: Standard-Dose LPV/r + RAL w/RBT 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 Study STARTED	24	24	23
Overall Study COMPLETED	21	19	21
Overall Study NOT COMPLETED	3	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	A: Standard-dose LPV/r w/RBT 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.	B: Double-dose LPV/r w/RIF 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.	C: Standard-Dose LPV/r + RAL w/RBT 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 Study Death	1	1	1
Overall Study Lost to Follow-up	1	2	0
Overall Study Unable to Get to Clinic	0	1	0
Overall Study Withdrawal by Subject	0	1	1
Overall Study Not Willing to Adhere to Requirements	1	0	0

Baseline Characteristics

Quantitative HIV RNA was summarized in the participants whose HIV RNA was above the assay's lower limit of quantification.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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 n=71 Participants Total of all reporting groups
Age, Continuous	42 years n=24 Participants	35 years n=24 Participants	38 years n=23 Participants	37 years n=71 Participants
Sex: Female, Male Female	13 Participants n=24 Participants	9 Participants n=24 Participants	15 Participants n=23 Participants	37 Participants n=71 Participants
Sex: Female, Male Male	11 Participants n=24 Participants	15 Participants n=24 Participants	8 Participants n=23 Participants	34 Participants n=71 Participants
Race/Ethnicity, Customized Black of African Origin	7 Participants n=24 Participants	8 Participants n=24 Participants	6 Participants n=23 Participants	21 Participants n=71 Participants
Race/Ethnicity, Customized Black African	8 Participants n=24 Participants	6 Participants n=24 Participants	4 Participants n=23 Participants	18 Participants n=71 Participants
Race/Ethnicity, Customized White	4 Participants n=24 Participants	2 Participants n=24 Participants	6 Participants n=23 Participants	12 Participants n=71 Participants
Race/Ethnicity, Customized Mixed Black	3 Participants n=24 Participants	5 Participants n=24 Participants	3 Participants n=23 Participants	11 Participants n=71 Participants
Race/Ethnicity, Customized Mestizo	2 Participants n=24 Participants	2 Participants n=24 Participants	2 Participants n=23 Participants	6 Participants n=71 Participants
Race/Ethnicity, Customized Mixed, of Predominantly African Ancestry	0 Participants n=24 Participants	0 Participants n=24 Participants	1 Participants n=23 Participants	1 Participants n=71 Participants
Race/Ethnicity, Customized Other	0 Participants n=24 Participants	1 Participants n=24 Participants	1 Participants n=23 Participants	2 Participants n=71 Participants
Region of Enrollment Haiti	6 participants n=24 Participants	6 participants n=24 Participants	6 participants n=23 Participants	18 participants n=71 Participants
Region of Enrollment Brazil	8 participants n=24 Participants	10 participants n=24 Participants	10 participants n=23 Participants	28 participants n=71 Participants
Region of Enrollment South Africa	4 participants n=24 Participants	3 participants n=24 Participants	3 participants n=23 Participants	10 participants n=71 Participants
Region of Enrollment Kenya	4 participants n=24 Participants	3 participants n=24 Participants	2 participants n=23 Participants	9 participants n=71 Participants
Region of Enrollment Peru	2 participants n=24 Participants	2 participants n=24 Participants	2 participants n=23 Participants	6 participants n=71 Participants
Qualitative HIV RNA Less than 40 copies/mL	4 Participants n=24 Participants	2 Participants n=24 Participants	3 Participants n=23 Participants	9 Participants n=71 Participants
Qualitative HIV RNA Greater than or equal to 40 copies/mL	20 Participants n=24 Participants	22 Participants n=24 Participants	20 Participants n=23 Participants	62 Participants n=71 Participants
Quantitative HIV RNA	4.7 log10 copies/mL n=20 Participants • Quantitative HIV RNA was summarized in the participants whose HIV RNA was above the assay's lower limit of quantification.	4.8 log10 copies/mL n=22 Participants • Quantitative HIV RNA was summarized in the participants whose HIV RNA was above the assay's lower limit of quantification.	4.2 log10 copies/mL n=20 Participants • Quantitative HIV RNA was summarized in the participants whose HIV RNA was above the assay's lower limit of quantification.	4.6 log10 copies/mL n=62 Participants • Quantitative HIV RNA was summarized in the participants whose HIV RNA was above the assay's lower limit of quantification.
CD4 Cell Count	128 cells/mm^3 n=24 Participants	117 cells/mm^3 n=24 Participants	158 cells/mm^3 n=23 Participants	130 cells/mm^3 n=71 Participants
Tuberculosis (TB) Diagnosis Certainty Confirmed Pulmonary TB	13 Participants n=24 Participants	8 Participants n=24 Participants	6 Participants n=23 Participants	27 Participants n=71 Participants
Tuberculosis (TB) Diagnosis Certainty Confirmed Extrapulmonary TB	1 Participants n=24 Participants	1 Participants n=24 Participants	3 Participants n=23 Participants	5 Participants n=71 Participants
Tuberculosis (TB) Diagnosis Certainty Confirmed Pulmonary and Extrapulmonary TB	1 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	1 Participants n=71 Participants
Tuberculosis (TB) Diagnosis Certainty Probable Pulmonary TB	9 Participants n=24 Participants	15 Participants n=24 Participants	13 Participants n=23 Participants	37 Participants n=71 Participants
Tuberculosis (TB) Diagnosis Certainty Probable Extrapulmonary TB	0 Participants n=24 Participants	0 Participants n=24 Participants	1 Participants n=23 Participants	1 Participants n=71 Participants
Acid Fast Bacilli (AFB) Smear Positive	11 Participants n=24 Participants	8 Participants n=24 Participants	6 Participants n=23 Participants	25 Participants n=71 Participants
Acid Fast Bacilli (AFB) Smear Negative	10 Participants n=24 Participants	14 Participants n=24 Participants	16 Participants n=23 Participants	40 Participants n=71 Participants
Acid Fast Bacilli (AFB) Smear No Results Available	3 Participants n=24 Participants	2 Participants n=24 Participants	1 Participants n=23 Participants	6 Participants n=71 Participants
Mycobacteria Tuberculosis (MTB) Culture MTB-Positive	13 Participants n=24 Participants	8 Participants n=24 Participants	9 Participants n=23 Participants	30 Participants n=71 Participants
Mycobacteria Tuberculosis (MTB) Culture MTB-Negative	6 Participants n=24 Participants	13 Participants n=24 Participants	13 Participants n=23 Participants	32 Participants n=71 Participants
Mycobacteria Tuberculosis (MTB) Culture No Results Available	5 Participants n=24 Participants	3 Participants n=24 Participants	1 Participants n=23 Participants	9 Participants n=71 Participants
Body Mass Index (BMI)	19.9 kg/m^2 n=24 Participants	20.4 kg/m^2 n=24 Participants	18.9 kg/m^2 n=23 Participants	19.6 kg/m^2 n=71 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: All randomized participants were included.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48.	58.3 percentage of participants Interval 38.8 to 75.5	66.7 percentage of participants Interval 46.7 to 82.0	60.9 percentage of participants Interval 40.8 to 77.8

SECONDARY outcome

Timeframe: 8 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=16 Participants 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.	B: Double-dose LPV/r w/RIF n=11 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=10 Participants 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.
Percent of Participants Who Experienced Sputum Conversion at Week 8.	87.5 percentage of participants Interval 64.0 to 96.5	81.8 percentage of participants Interval 52.3 to 94.9	70.0 percentage of participants Interval 39.7 to 89.2

SECONDARY outcome

Timeframe: After 16 weeks and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Who Experienced TB Treatment Failure	0.0 percentage of participants Interval 0.0 to 13.8	0.0 percentage of participants Interval 0.0 to 13.8	0.0 percentage of participants Interval 0.0 to 14.3

SECONDARY outcome

Timeframe: At or after 24 weeks and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Who Experienced TB Relapse/Recurrence	0.0 percentage of participants Interval 0.0 to 13.8	4.2 percentage of participants Interval 0.7 to 20.2	4.3 percentage of participants Interval 0.8 to 21.0

SECONDARY outcome

Timeframe: At or after 24 weeks and through week 72

Population: All participants who experienced TB relapse/recurrence were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT 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.	B: Double-dose LPV/r w/RIF n=1 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=1 Participants 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.
Percent of Participants Who Experienced TB Relapse/Recurrence and Who Had TB Drug Resistance	—	0 participants Interval 0.0 to 79.3	0 participants Interval 0.0 to 32.4

SECONDARY outcome

Timeframe: 48 weeks

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Whose HIV Viral Load Was Less Than 50 Copies/mL at Week 48	45.8 percentage of participants Interval 27.9 to 64.9	54.2 percentage of participants Interval 35.1 to 72.1	56.5 percentage of participants Interval 36.8 to 74.4

SECONDARY outcome

Timeframe: After randomization and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Number of Participants Reporting a Grade 3 or 4 Sign or Symptom	7 Participants	5 Participants	5 Participants

SECONDARY outcome

Timeframe: After randomization and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Number of Participants Reporting a Grade 3 or 4 Laboratory Abnormality	6 Participants	3 Participants	5 Participants

SECONDARY outcome

Timeframe: After randomization and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Who Interrupted or Discontinued at Least One HIV Drug Due to Toxicity	20.8 percentage of participants Interval 9.2 to 40.5	16.7 percentage of participants Interval 6.7 to 35.9	21.7 percentage of participants Interval 9.7 to 41.9

SECONDARY outcome

Timeframe: After randomization and through to the discontinuation of the last TB drug

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Who Interrupted or Discontinued at Least One TB Drug Due to Toxicity	20.8 percentage of participants Interval 9.2 to 40.5	8.3 percentage of participants Interval 2.3 to 25.8	13.0 percentage of participants Interval 4.5 to 32.1

SECONDARY outcome

Timeframe: At weeks 16, 24, 48, and 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Who Experienced HIV Virologic Failure	29.2 percentage of participants Interval 14.9 to 49.2	50.0 percentage of participants Interval 31.4 to 68.6	30.4 percentage of participants Interval 15.6 to 50.9

SECONDARY outcome

Timeframe: At weeks 16, 24, 48, and 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Cumulative Probability of HIV Virologic Failure at Week 72	29.2 cumulative events per 100 participants Interval 15.1 to 51.6	50.0 cumulative events per 100 participants Interval 32.2 to 70.9	30.4 cumulative events per 100 participants Interval 15.8 to 53.4

SECONDARY outcome

Timeframe: After randomization and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Number of Participants Who Experienced MTB IRIS	1 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: Participants who had CD4 cell count data available at baseline and week 8 were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=22 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=22 Participants 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.
CD4 Count Change From Baseline to Week 8	7 cells/mm^3 Interval -71.0 to 33.0	26 cells/mm^3 Interval 2.0 to 106.0	37 cells/mm^3 Interval -60.0 to 79.0

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Participants who had CD4 cell count data available at baseline and week 24 were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=21 Participants 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.	B: Double-dose LPV/r w/RIF n=23 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=18 Participants 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.
CD4 Count Change From Baseline to Week 24	20 cells/mm^3 Interval -38.0 to 56.0	56 cells/mm^3 Interval 12.0 to 110.0	13 cells/mm^3 Interval -64.0 to 100.0

SECONDARY outcome

Timeframe: Baseline and 48 weeks

Population: Participants who had CD4 cell count data available at baseline and week 48 were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=20 Participants 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.	B: Double-dose LPV/r w/RIF n=20 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=18 Participants 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.
CD4 Count Change From Baseline to Week 48	99 cells/mm^3 Interval 1.0 to 159.0	119 cells/mm^3 Interval 57.0 to 263.0	74 cells/mm^3 Interval 16.0 to 115.0

SECONDARY outcome

Timeframe: Baseline and 72 weeks

Population: Participants who had CD4 cell count data available at baseline and week 72 were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=20 Participants 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.	B: Double-dose LPV/r w/RIF n=19 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=20 Participants 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.
CD4 Count Change From Baseline to Week 72	126 cells/mm^3 Interval 26.0 to 247.0	212 cells/mm^3 Interval 93.0 to 281.0	54 cells/mm^3 Interval -6.0 to 203.0

SECONDARY outcome

Timeframe: After randomization and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Who Experienced a New AIDS-defining Illness	0.0 percentage of participants Interval 0.0 to 13.8	4.2 percentage of participants Interval 0.7 to 20.2	0.0 percentage of participants Interval 0.0 to 14.3

SECONDARY outcome

Timeframe: After randomization and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Who Died	4.2 percentage of participants Interval 0.7 to 20.2	4.7 percentage of participants Interval 0.7 to 20.2	4.3 percentage of participants Interval 0.8 to 21.0

SECONDARY outcome

Timeframe: After randomization and through week 72

Population: All randomized participants were included.

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=24 Participants 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.	B: Double-dose LPV/r w/RIF n=24 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=23 Participants 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.
Percent of Participants Who Experienced a New AIDS-defining Illness or Died	4.2 percentage of participants Interval 0.7 to 20.2	8.3 percentage of participants Interval 2.3 to 25.8	4.3 percentage of participants Interval 0.8 to 21.0

OTHER_PRE_SPECIFIED outcome

Timeframe: At 2 weeks: pre-dose and at 2, 4, 5, and 6 hours post-dose

Population: 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).

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=19 Participants 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.	B: Double-dose LPV/r w/RIF n=17 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=14 Participants 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.
LPV Cmax and Cmin in Participants Enrolled in Arms A, B, and C Maximum Concentration (Cmax)	18531 ng/mL Interval 12978.0 to 21627.0	18138 ng/mL Interval 11366.0 to 22807.0	16802 ng/mL Interval 12609.0 to 24924.0
LPV Cmax and Cmin in Participants Enrolled in Arms A, B, and C Minimum Concentration (Cmin)	9920 ng/mL Interval 2421.0 to 16127.0	8033 ng/mL Interval 4061.0 to 9481.0	8548 ng/mL Interval 5603.0 to 15968.0

OTHER_PRE_SPECIFIED outcome

Timeframe: At 2 weeks: pre-dose and at 2, 4, 5, and 6 hours post-dose

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=19 Participants 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.	B: Double-dose LPV/r w/RIF n=17 Participants 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.	C: Standard-Dose LPV/r + RAL w/RBT n=14 Participants 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.
LPV AUC in Participants Enrolled in Arms A, B, and C	159796 hours*ng/mL Interval 113493.0 to 222251.0	161772 hours*ng/mL Interval 102118.0 to 209509.0	149247 hours*ng/mL Interval 122324.0 to 243273.0

OTHER_PRE_SPECIFIED outcome

Timeframe: At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose

Population: 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).

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=18 Participants 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.	B: Double-dose LPV/r w/RIF 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.	C: Standard-Dose LPV/r + RAL w/RBT n=11 Participants 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.
RBT Cmax and Cmin in Participants Enrolled in Arms A and C Maximum Concentration (Cmax)	461 ng/mL Interval 361.0 to 625.0	—	349 ng/mL Interval 249.0 to 505.0
RBT Cmax and Cmin in Participants Enrolled in Arms A and C Minimum Concentration (Cmin)	161 ng/mL Interval 104.0 to 255.0	—	115 ng/mL Interval 88.0 to 171.0

OTHER_PRE_SPECIFIED outcome

Timeframe: At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT n=18 Participants 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.	B: Double-dose LPV/r w/RIF 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.	C: Standard-Dose LPV/r + RAL w/RBT n=11 Participants 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.
RBT AUC in Participants Enrolled in Arms A and C	7374 hours*ng/mL Interval 5909.0 to 11785.0	—	5516 hours*ng/mL Interval 4147.0 to 7060.0

OTHER_PRE_SPECIFIED outcome

Timeframe: At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose

Population: 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).

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT 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.	B: Double-dose LPV/r w/RIF 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.	C: Standard-Dose LPV/r + RAL w/RBT n=16 Participants 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.
RAL Cmax and Cmin in Participants Enrolled in Arm C Maximum Concentration (Cmax)	—	—	2830 ng/mL Interval 469.0 to 4560.0
RAL Cmax and Cmin in Participants Enrolled in Arm C Minimum Concentration (Cmin)	—	—	166 ng/mL Interval 53.0 to 197.0

OTHER_PRE_SPECIFIED outcome

Timeframe: At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose

Population: 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).

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.

Outcome measures

Outcome measures
Measure	A: Standard-dose LPV/r w/RBT 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.	B: Double-dose LPV/r w/RIF 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.	C: Standard-Dose LPV/r + RAL w/RBT n=16 Participants 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.
RAL AUC in Participants Enrolled in Arm C	—	—	11338 hours*ng/mL Interval 2618.0 to 15363.0

Adverse Events

A: Standard-dose LPV/r w/RBT

Serious events: 4 serious events

Other events: 24 other events

Deaths: 1 deaths

B: Double-dose LPV/r w/RIF

Serious events: 5 serious events

Other events: 23 other events

Deaths: 1 deaths

C: Standard-Dose LPV/r + RAL w/RBT

Serious events: 5 serious events

Other events: 23 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
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