Trial Outcomes & Findings for Rifaximin as a Modulator of Microbial Translocation and Immune Activation (NCT NCT01466595)

NCT ID: NCT01466595

Last Updated: 2018-09-10

Results Overview

Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from baseline to week 4, where the baseline value is the average of pre-entry and entry values.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 73 participants
• Primary outcome timeframe: At baseline and 4 weeks
• Results posted on: 2018-09-10

Participant Flow

A5286 opened under version 2.0 on 09/01/11, and the first subject was randomized on 10/03/11. Accrual to the study closed on 07/30/12, with a total of 73 subjects enrolled from 32 sites within the US.

Subjects were randomized with a 2:1 ratio (Rifaximin : no study treatment) at enrollment.

Participant milestones

Measure	Arm A: Treatment With Rifaximin Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment No study treatment for 4 weeks
Overall Study STARTED	49	24
Overall Study COMPLETED	49	23
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Arm A: Treatment With Rifaximin Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment No study treatment for 4 weeks
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Rifaximin as a Modulator of Microbial Translocation and Immune Activation

Baseline characteristics by cohort

Measure	Arm A: Treatment With Rifaximin n=49 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=24 Participants No study treatment for 4 weeks	Total n=73 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=5 Participants	24 Participants n=7 Participants	70 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	49.5 years STANDARD_DEVIATION 8.1 • n=5 Participants	49.7 years STANDARD_DEVIATION 9.7 • n=7 Participants	49.6 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	22 Participants n=7 Participants	67 Participants n=5 Participants
Region of Enrollment United States	49 participants n=5 Participants	24 participants n=7 Participants	73 participants n=5 Participants
Number of participants with HIV-1 RNA below assay lower limit	49 participants n=5 Participants	24 participants n=7 Participants	73 participants n=5 Participants
CD4 count	240 cells/mm^3 n=5 Participants	223 cells/mm^3 n=7 Participants	236 cells/mm^3 n=5 Participants

PRIMARY outcome

Timeframe: At baseline and 4 weeks

Population: The primary analysis is as-treated, limited to subjects who had data for both baseline and week 4, and (for the rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change antiretroviral therapy (ART) or use prohibited medications or have virologic failure during this time period.

Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from baseline to week 4, where the baseline value is the average of pre-entry and entry values.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in CD8+ T-cell Activation From Baseline to Week 4	0.00 percentage HLA-DR+/CD38+ of CD8+ Interval -1.7 to 1.0	0.64 percentage HLA-DR+/CD38+ of CD8+ Interval 0.11 to 1.48

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in D-dimer from baseline to week 4, where baseline value is the average of pre-entry and entry.

D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in D-dimer From Baseline to Week 4	0.00 log10 ng/mL Interval -0.12 to 0.06	-0.03 log10 ng/mL Interval -0.14 to 0.04

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in Interleukin (IL)-6 from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in IL-6 From Baseline to Week 4	-0.03 log10 pg/mL Interval -0.14 to 0.08	0.05 log10 pg/mL Interval -0.13 to 0.12

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in Lipopolysaccharide (LPS) from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in LPS From Baseline to Week 4	0.00 log10 pg/mL Interval -0.08 to 0.05	-0.01 log10 pg/mL Interval -0.04 to 0.05

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in High Sensitivity C-reactive Protein (Hs-CRP) from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in hsCRP From Baseline to Week 4	-0.08 log10 ng/mL Interval -0.29 to 0.15	-0.09 log10 ng/mL Interval -0.21 to 0.16

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in soluble CD14 (sCD14) from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in sCD14 From Baseline to Week 4	-0.03 log10 ng/mL Interval -0.07 to 0.06	-0.03 log10 ng/mL Interval -0.05 to 0.01

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in gut-homing percent B7hi+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in Peripheral B7hi CD4+ T-cell From Baseline to Week 4	-0.40 percentage B7hi+ of CD4+ Interval -1.28 to 0.41	0.00 percentage B7hi+ of CD4+ Interval -0.72 to 0.68

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in advanced flow percent CD38+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %CD38+ of CD4+ From Baseline to Week 4	0.89 percentage CD38+ of CD4+ Interval -2.04 to 2.99	0.91 percentage CD38+ of CD4+ Interval -0.35 to 2.06

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in advanced flow percent CD38+ of CD8+ from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %CD38+ of CD8+ From Baseline to Week 4	0.21 percentage CD38+ of CD8+ Interval -4.14 to 2.52	0.66 percentage CD38+ of CD8+ Interval 0.18 to 3.03

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in advanced flow percent Ki67+ of CD4+ from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %Ki67+ of CD4+ From Baseline to Week 4	-0.17 percentage Ki67+ of CD4+ Interval -0.47 to 0.25	0.05 percentage Ki67+ of CD4+ Interval -0.36 to 0.51

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in advanced flow percent Ki67+ of CD8+ from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %Ki67+ of CD8+ From Baseline to Week 4	-0.12 percentage Ki67+ of CD8+ Interval -0.27 to 0.12	0.12 percentage Ki67+ of CD8+ Interval -0.07 to 0.27

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in CD4 activation percent co-expressing HLA-DR and CD38 from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %HLA-DR+/CD38+ of CD4+ From Baseline to Week 4	-0.15 percentage HLA-DR+/CD38+ of CD4+ Interval -1.03 to 0.99	0.15 percentage HLA-DR+/CD38+ of CD4+ Interval -0.59 to 0.86

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in CD38+ of CD8+ MFI (Median Fluorescence Intensity) from baseline to week 4, where baseline value is the average of pre-entry and entry.

MFI measures the shift in fluorescence intensity of a population of cells. MFI values are based on control to demonstrate an increase or decrease in expression of the marker. MFI in this study was automatically calculated in FlowJo. The median is the relative intensity value below which 50% of the events are found. MFI is an arbitrary unit of relative intensity.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in CD38+ of CD8+ MFI From Baseline to Week 4	0.00 MFI (relative intensity) Interval -0.04 to 0.07	0.03 MFI (relative intensity) Interval 0.0 to 0.07

SECONDARY outcome

Timeframe: At baseline and 4 weeks

Population: This analysis is as-treated, limited to subjects who have data for baseline and week 4, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure during this time period.

Change in total CD4 T-cell from baseline to week 4, where baseline value is the average of pre-entry and entry

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in CD4 Count From Baseline to Week 4	-3.00 cells/mm3 Interval -20.5 to 31.0	11.25 cells/mm3 Interval -9.0 to 52.0

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who had data for both week 4 and week 8, and (for the rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8.

Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in CD8+ T-cell Activation From Week 4 to Week 8	0.08 percentage HLA-DR+/CD38+ of CD8+ Interval -0.7 to 0.7	-0.71 percentage HLA-DR+/CD38+ of CD8+ Interval -1.85 to 0.56

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in D-dimer From Week 4 to Week 8	-0.02 log10 ng/mL Interval -0.1 to 0.09	0.03 log10 ng/mL Interval -0.03 to 0.17

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in IL-6 from week 4 to week 8.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in IL-6 From Week 4 to Week 8	-0.03 log10 pg/mL Interval -0.18 to 0.08	0.06 log10 pg/mL Interval -0.01 to 0.19

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in LPS from week 4 to week 8.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in LPS From Week 4 to Week 8	-0.01 log10 pg/mL Interval -0.08 to 0.02	0.00 log10 pg/mL Interval -0.03 to 0.07

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in hsCRP from week 4 to week 8.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in hsCRP From Week 4 to Week 8	-0.05 log10 ng/mL Interval -0.29 to 0.2	0.23 log10 ng/mL Interval 0.06 to 0.5

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in soluble CD14 from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in sCD14 From Week 4 to Week 8	-0.05 log10 ng/mL Interval -0.11 to 0.04	0.02 log10 ng/mL Interval -0.03 to 0.05

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in gut homing percent B7hi+ of CD4+ from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 8	0.26 percentage B7hi+ of CD4+ Interval -0.37 to 0.97	-0.02 percentage B7hi+ of CD4+ Interval -0.82 to 1.06

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in advanced flow percent CD38+ of CD4+ from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in %CD38+ of CD4+ From Week 4 to Week 8	-0.84 percentage CD38+ of CD4+ Interval -3.2 to 1.33	1.00 percentage CD38+ of CD4+ Interval -1.88 to 2.92

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in advanced flow percent CD38+ of CD8+ from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in %CD38+ of CD8+ From Week 4 to Week 8	-0.12 percentage CD38+ of CD8+ Interval -2.3 to 2.09	-1.20 percentage CD38+ of CD8+ Interval -3.04 to 1.84

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in advanced flow percent Ki67+ of CD4+ from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in %Ki67+ of CD4+ From Week 4 to Week 8	0.21 percentage Ki67+ of CD4+ Interval -0.17 to 0.53	-0.01 percentage Ki67+ of CD4+ Interval -0.58 to 0.51

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in advanced flow percent Ki67+ of CD8+ from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in %Ki67+ of CD8+ From Week 4 to Week 8	0.11 percentage Ki67+ of CD8+ Interval -0.05 to 0.23	-0.08 percentage Ki67+ of CD8+ Interval -0.21 to 0.06

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in CD4 activation percent co-expressing HLA-DR and CD38 from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in CD4 Activation Percent From Week 4 to Week 8	0.17 percentage HLA-DR+/CD38+ of CD4+ Interval -0.66 to 0.86	-0.53 percentage HLA-DR+/CD38+ of CD4+ Interval -0.85 to 0.31

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in CD38+ of CD8+ median fluorescence intensity (MFI) from week 4 to week 8.

MFI measures the shift in fluorescence intensity of a population of cells. MFI values are based on control to demonstrate an increase or decrease in expression of the marker. MFI in this study was automatically calculated in FlowJo. The median is the relative intensity value below which 50% of the events are found. MFI is an arbitrary unit of relative intensity.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in CD38+ of CD8+ MFI From Week 4 to Week 8	0.08 MFI (relative intensity) Interval -0.7 to 0.7	-0.71 MFI (relative intensity) Interval -1.85 to 0.56

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 8, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 8

Change in total CD4 T-cell count from week 4 to week 8

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=21 Participants No study treatment for 4 weeks
Change in CD4 Count From Week 4 to Week 8	-9.50 cells/mm3 Interval -26.0 to 9.0	-13.00 cells/mm3 Interval -30.0 to 5.0

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who had data for both week 4 and week 12, and (for the rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in CD8+ T-cell activation percent co-expressing HLA-DR and CD38 from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in CD8+ T-cell Activation From Week 4 to Week 12	-0.05 percentage HLA-DR+/CD38+ of CD8+ Interval -0.76 to 1.0	-0.77 percentage HLA-DR+/CD38+ of CD8+ Interval -2.91 to 0.23

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in D-dimer From Week 4 to Week 12	-0.01 log10 ng/mL Interval -0.1 to 0.09	0.07 log10 ng/mL Interval -0.02 to 0.1

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in IL-6 from week 4 to week 12.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in IL-6 From Week 4 to Week 12	0.02 log10 pg/mL Interval -0.13 to 0.25	0.02 log10 pg/mL Interval -0.21 to 0.15

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in LPS from week 4 to week 12.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in LPS From Week 4 to Week 12	0.00 log10 pg/mL Interval -0.09 to 0.04	0.03 log10 pg/mL Interval -0.01 to 0.12

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in hsCRP from week 4 to week 12.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in hsCRP From Week 4 to Week 12	0.09 log10 ng/mL Interval -0.13 to 0.28	0.04 log10 ng/mL Interval -0.08 to 0.27

SECONDARY outcome

Timeframe: At weeks 4 and 8

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in soluble CD14 from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=43 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in sCD14 From Week 4 to Week 12	0.03 log10 ng/mL Interval -0.03 to 0.08	0.02 log10 ng/mL Interval -0.05 to 0.1

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in gut homing percent B7hi+ of CD4+ from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=41 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in Peripheral B7hi CD4+ T-cells From Week 4 to Week 12	-0.07 percentage B7hi+ of CD4+ Interval -0.57 to 0.69	-0.19 percentage B7hi+ of CD4+ Interval -0.98 to 0.11

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12

Change in advanced flow percent CD38+ of CD4+ from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %CD38+ of CD4+ From Week 4 to Week 12	-0.67 percentage CD38+ of CD4+ Interval -3.81 to 2.91	-0.54 percentage CD38+ of CD4+ Interval -4.82 to 1.81

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in advanced flow percent CD38+ of CD8+ from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %CD38+ of CD8+ From Week 4 to Week 12	-0.93 percentage CD38+ of CD8+ Interval -3.6 to 2.4	-1.96 percentage CD38+ of CD8+ Interval -6.5 to 0.6

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12

Change in advanced flow percent Ki67+ of CD4+ from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %Ki67+ of CD4+ From Week 4 to Week 12	0.14 percentage Ki67+ of CD4+ Interval -0.23 to 0.79	-0.22 percentage Ki67+ of CD4+ Interval -0.85 to 0.32

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12

Change in advanced flow percent Ki67+ of CD8+ from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in %Ki67+ of CD8+ From Week 4 to Week 12	0.13 percentage Ki67+ of CD8+ Interval -0.11 to 0.37	-0.09 percentage Ki67+ of CD8+ Interval -0.16 to 0.16

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in CD4 activation percent co-expressing HLA-DR and CD38 from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in CD4 Activation Percent From Week 4 to Week 12	-0.14 percentage HLA-DR+/CD38+ of CD4+ Interval -0.7 to 1.03	-0.50 percentage HLA-DR+/CD38+ of CD4+ Interval -1.65 to 0.16

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in CD38+ of CD8+ median fluorescence intensity (MFI) from week 4 to week 12.

MFI measures the shift in fluorescence intensity of a population of cells. MFI values are based on control to demonstrate an increase or decrease in expression of the marker. MFI in this study was automatically calculated in FlowJo. The median is the relative intensity value below which 50% of the events are found. MFI is an arbitrary unit of relative intensity.

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in CD38+ of CD8+ MFI From Week 4 to Week 12	-0.02 MFI (relative intensity) Interval -0.06 to 0.04	-0.02 MFI (relative intensity) Interval -0.09 to 0.03

SECONDARY outcome

Timeframe: At weeks 4 and 12

Population: This analysis is as-treated, limited to subjects who have data for week 4 and week 12, and (for the Rifaximin arm) remain on study treatment through week 4 (allowing less than or equal to 6 missed doses), and did not change ART or use prohibited medications or have virologic failure prior to week 12.

Change in total CD4 T-cell count from week 4 to week 12

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=42 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=22 Participants No study treatment for 4 weeks
Change in CD4 Count From Week 4 to Week 12	0.00 cells/mm3 Interval -26.0 to 20.0	-5.50 cells/mm3 Interval -44.0 to 39.0

SECONDARY outcome

Timeframe: from study enrollment until study completion at 12 weeks

Primary adverse events include all SAEs, defined according to ICH guidelines and targeted protocol events (grade 2 or higher signs and symptoms, grade 2 or higher laboratory abnormality, all diagnoses identified by the ACTG criteria for clinical events, and all events that led to a change in treatment regardless of grade).

Outcome measures

Measure	Arm A: Treatment With Rifaximin n=49 Participants Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=24 Participants No study treatment for 4 weeks
Primary Adverse Events	27 participants	9 participants

Adverse Events

Arm A: Treatment With Rifaximin

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Arm B: No Study Treatment

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Arm A: Treatment With Rifaximin n=49 participants at risk Participants were administered one 550 mg tablet of rifaximin to be taken orally two times a day for 4 weeks.	Arm B: No Study Treatment n=24 participants at risk No study treatment for 4 weeks
Gastrointestinal disorders Diarrhoea	6.1% 3/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Gastrointestinal disorders Flatulence	6.1% 3/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Gastrointestinal disorders Nausea	8.2% 4/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Gastrointestinal disorders Vomiting	6.1% 3/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
General disorders Fatigue	8.2% 4/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	4.2% 1/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
General disorders Pyrexia	6.1% 3/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	4.2% 1/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood bilirubin increased	14.3% 7/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	8.3% 2/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood cholesterol increased	36.7% 18/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	50.0% 12/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood creatinine increased	4.1% 2/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	8.3% 2/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood glucose increased	14.3% 7/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	20.8% 5/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood phosphorus decreased	4.1% 2/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	12.5% 3/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood sodium decreased	8.2% 4/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	8.3% 2/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Blood uric acid increased	2.0% 1/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	16.7% 4/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Lipase abnormal	0.00% 0/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	8.3% 2/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Lipase increased	4.1% 2/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	8.3% 2/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Low density lipoprotein increased	22.4% 11/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	37.5% 9/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Neutrophil count decreased	12.2% 6/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations Platelet count decreased	2.0% 1/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	8.3% 2/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Investigations White blood cell count decreased	8.2% 4/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Metabolism and nutrition disorders Decreased appetite	6.1% 3/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	0.00% 0/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
Nervous system disorders Headache	8.2% 4/49 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).	4.2% 1/24 • AEs reported from study enrollment until study completion at 12 weeks AE reporting followed DAIDS Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Email: ACTGCT.Gov@s-3.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place