Trial Outcomes & Findings for The Role of Probiotics in HIV Patients With Immunological Non-Responder (NCT NCT03568812)

Last Updated: 2025-05-04

Results Overview

CD4 level in blood (cell/μL) indicate immune status of patient receiving probiotics or placebo, measure between baseline and at 12 weeks of intervention. Analysis will include CD4 T cell levels after intervention, adjusted with duration of ARV therapy and baseline CD4 levels, as well as unadjusted.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

12 weeks

Results posted on

2025-05-04

Participant Flow

Study recruitment was done between May and August 2018, study observation was done for 90-day for each subject and completed in October 2018. During study period patient was recruited consecutively on the day of policlinic visit by evaluate the existing medical record data included (1) data of CD4+ T cell and (2) viral load data at least one year ago (3) using ARV for at least 6-month.

Eligible patient was offered and signed informed consent while agree to participate. Total of 1771 patients visited POKDISUS. Completed data was available for 111 patients and 80 patients gave informed consent to participate.

Participant milestones

Participant milestones
Measure	Probiotics Rillus® Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
Overall Study STARTED	40	40
Overall Study COMPLETED	40	39
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Probiotics Rillus® Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
Overall Study Physician Decision	0	1

Baseline Characteristics

The Role of Probiotics in HIV Patients With Immunological Non-Responder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Probiotics Rillus® n=40 Participants Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo n=40 Participants Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Total n=80 Participants Total of all reporting groups
Age, Continuous	40.9 years STANDARD_DEVIATION 6.7 • n=5 Participants	38.2 years STANDARD_DEVIATION 6.5 • n=7 Participants	39.5 years STANDARD_DEVIATION 6.7 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	28 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Ambon	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Batak	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Betawi	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Javanese	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Makassar	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Padang	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Palembang	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Riau	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Sumatran	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Sundanese	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Chinese	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Other	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Th17 Level	1.4 cell/μL n=5 Participants	1.6 cell/μL n=7 Participants	1.5 cell/μL n=5 Participants
CD4+ level	265 cell/μL n=5 Participants	389 cell/μL n=7 Participants	327 cell/μL n=5 Participants
Fecal Calprotectin Level	6.4 μg/g n=5 Participants	6.1 μg/g n=7 Participants	6.3 μg/g n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: The results was divided in to unadjusted and adjusted CD4 level change

Outcome measures

Outcome measures
Measure	Probiotics Rillus® n=40 Participants Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo n=39 Participants Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
CD4+ Level The result of unadjusted CD4 level change	162.3 cell/μL Interval 112.5 to 212.1	50.5 cell/μL Interval 0.5 to 100.9
CD4+ Level The result of adjusted CD4 level change	143.3 cell/μL Interval 96.9 to 189.7	69.9 cell/μL Interval 22.9 to 117.0

SECONDARY outcome

Timeframe: 12 weeks

Population: The results was divided in to unadjusted and adjusted Th17 level change

Change in Th17 level in blood to assess improvement of gut mucosal integrity and immunity between baseline and at 12 weeks, measured in cell/μL The results was divided in to unadjusted and adjusted Th17 level change.

Outcome measures

Outcome measures
Measure	Probiotics Rillus® n=40 Participants Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo n=39 Participants Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
Th17 Level Change The results of unadjusted Th17 level change	-0.5 cell/μL Interval -1.0 to 0.1	-0.2 cell/μL Interval -1.8 to 0.3
Th17 Level Change The results of adjusted Th17 level change	-0.3 cell/μL Interval -0.8 to 0.2	-0.4 cell/μL Interval -0.9 to 0.1

SECONDARY outcome

Timeframe: 12 weeks

Population: 16S rRNA gene level was measured in all participant before and after intervention. The results were undetected in all participants.

Total of 16SrRNA of translocated gut bacteria in blood, measured in copies/mL, presented as median and interquartile range.

Outcome measures

Outcome measures
Measure	Probiotics Rillus® n=40 Participants Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo n=39 Participants Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
16S Ribosomal RNA (rRNA) Total	NA copies/mL All results are under detection limit.	NA copies/mL All results are under detection limit.

SECONDARY outcome

Timeframe: 12 weeks

Population: The results are divided in to unadjusted and adjusted fecal calprotectin level change

Change in calprotectin level in feces to assess gut inflammation between baseline and at 12 weeks, measured in μg/g. The results was divided in to unadjusted and adjusted fecal calprotectin level change

Outcome measures

Outcome measures
Measure	Probiotics Rillus® n=40 Participants Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo n=39 Participants Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
Fecal Calprotectin Level Change The result of unadjusted fecal calprotectin level change	-4.3 μg/g Interval -12.3 to 3.6	8.4 μg/g Interval 0.4 to 16.3
Fecal Calprotectin Level Change The result of adjusted fecal calprotectin level change	-5.8 μg/g Interval -14.0 to 2.4	9.9 μg/g Interval 1.6 to 18.1

SECONDARY outcome

Timeframe: 0,4,8,12 weeks

Population: The results was divided into somatic and psychological symptoms. Both of them were divided again into unadjusted and adjusted HIV Symptoms Index score Change.

A questionnaire called HIV Symptoms Index (Have been validated in Indonesian language) containing self administered 20 questions consisted of 15 somatic and 5 psychological symptoms to assess Human Immunodeficiency Virus (HIV) related symptoms in patients. The total score is calculated by summing the numbers of each symptom (0 = no symptoms, 1 = no disturbing symptoms, 2 = there are symptoms that are a little annoying, 3 = there are disturbing symptoms, 4 = there are very disturbing symptoms), with a minimum score of 0 and maximum 80. Somatic symptoms range from 0-60 and psychological symptoms range from 0-20. An increase in score indicates a worsening condition. Change in HIV Symptoms Index score to assess improvement of somatic and psychological symptoms between baseline and at 12 weeks. The results was divided into somatic and psychological symptoms. Both of them were divided again into unadjusted and adjusted HIV Symptoms Index score Change.

Outcome measures

Outcome measures
Measure	Probiotics Rillus® n=40 Participants Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo n=39 Participants Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
Amount of Participants With HIV Related Symptoms The results of unadjusted somatic HIV Symptoms Index score Change	-1.6 score on a scale Interval -3.2 to 0.04	-1.3 score on a scale Interval -2.9 to 0.3
Amount of Participants With HIV Related Symptoms The results of adjusted somatic HIV Symptoms Index score Change	-1.4 score on a scale Interval -2.9 to 0.2	-1.11 score on a scale Interval -2.76 to 0.55
Amount of Participants With HIV Related Symptoms The results of unadjusted psychological HIV Symptoms Index score Change	-0.6 score on a scale Interval -1.2 to 0.09	-0.1 score on a scale Interval -0.8 to 0.5
Amount of Participants With HIV Related Symptoms The results of adjusted psychological HIV Symptoms Index score Change	-0.6 score on a scale Interval -1.3 to 0.03	0.05 score on a scale Interval -0.7 to 0.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 0,4, 8, 12 weeks

Population: The food frequency is divided in to 2 categories "often and seldom" consume "tempeh" after 12 weeks.

Food Frequency Questionnaire (FFQ): A questionnaire consisted of food and drink list and frequency to assess patients' dietary pattern in the past one week. Nutritionist will be asking the participants for the questionnaire questions. The food frequency scaled to "more than one time daily", "once daily", "3-6 times in one week", "1-2 times in one week", "less than one time in one week", "never". We assessed changes in tempeh consumption (as part of FFQ question) after the 12-week intervention by categorizing participants into two groups based on their post-intervention intake: 'seldom' (consuming tempeh 1-2 times per week) and 'often' (consuming tempeh daily). The number of participants in each category was then recorded.

Outcome measures

Outcome measures
Measure	Probiotics Rillus® n=40 Participants Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo n=39 Participants Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
Change in Food Frequency consume tempeh 1-2 times in one week.	22 participants	23 participants
Change in Food Frequency consume tempeh once a day.	13 participants	10 participants

Adverse Events

Probiotics Rillus®

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Probiotics Rillus® n=40 participants at risk Rillus®, Chewing tablet containing viable cell 1.0 x 10\^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Rillus®: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.	Placebo n=40 participants at risk Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Placebo: Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
Gastrointestinal disorders Constipation	0.00% 0/40 • 12 weeks	5.0% 2/40 • Number of events 2 • 12 weeks
Gastrointestinal disorders Diarrhea	2.5% 1/40 • Number of events 1 • 12 weeks	2.5% 1/40 • Number of events 1 • 12 weeks

Additional Information

Dr dr. Erni Juwita Nelwan, Ph.D, Sp.PD-KPTI

Tropical and Infectious Disease Division, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, Indonesia

Phone: +62811961229

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place