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

May 2, 2025 updated by: Erni J. Nelwan, Indonesia University

The Role of Probiotics L. Plantarum, S. Thermophiles, B. Bifidum on Gut Inflammation, Bacterial Translocation, and CD4+ Cell Count in HIV Patients With Immunological Non-Responder

This study will address HIV patients who are on antiretroviral treatment (ART) and experiencing immunological failure. The cause of immunological failure in HIV patients could be due to several factors such as age, gender, Cluster of Differentiation (CD4)+ count before started treatment and some inflammation in the gut. The C-C Chemokine Receptor 5 (CCR5) receptor on T lymphocyte CD4+ are abundantly found in the gut and attacked by HIV virus during acute infection causing irreversible damage.

The disruption of gut integrity and chronic inflammation further causing translocation of bacteria in gut lumen to the blood. Thus resulting persistent low CD4+ or immunological failure.

This evaluation plan is designed to establish the role of investigation product (probiotics) to improve gut inflammation in HIV patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

HIV patients could develop immunological failure despite being treated with antiretroviral therapy (ART). Thus resulting the increase of morbidity and mortality among HIV patients, especially in Indonesia. The immunological failure is associated with decreased gut integrity and immunity, increased gut inflammation, and gut bacterial translocation to the blood. Memory CD4+ T cell damage in gut associated lymphoid tissue (GALT) by HIV-1 virus leads to decreased production of Th17 in gut mucosal layer. Furthermore, low level of Th17 facilitates bacterial translocation in HIV patients.

Probiotic supplementation (Lactobacillus) could decrease the gut inflammation in some diseases including HIV infection; thus helps increasing the gut integrity and immunity by repairing the gut mucosal tight junction, increasing mucin production, and regulating gut Th17. As a result, the gut inflammation and bacterial translocation decreases. Nevertheless, the benefit in HIV patients with immunological non responder status has not been established.

The investigators plan to perform double blind randomized clinical trial of probiotics (containing Lactobacillus plantarum, Streptococcus thermophiles, Bifidobacterium bifidum) in HIV patients with immunological non responder status. The Subject who fulfill inclusion criteria, willing to participate and sign informed consent will be randomized into two groups: the group receiving probiotics (n=40) and the group of placebo (n=40). Intervention will be held for 12 weeks. This study will evaluate the gut mucosal integrity and immunity by Th17 measurement; bacterial translocation by 16S ribosomal RNA (16S RNA) measurement; and gut inflammation by fecal calprotectin measurement before and after the intervention. Moreover, the investigators will measure the CD4+ level to assess immune status recovery before and after the intervention. Side effects, HIV symptom index, Food Frequency Questionnaire will also be assessed every 4 weeks.

Statistical analysis will uses: paired and independent t test (if normally distributed) or using Wilcoxon and Mann Whitney test (if not normally distributed). HIV symptom index and Food frequency will be reported descriptively.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
      • Jakarta, Indonesia, 10430
        • HIV Clinic, Cipto Mangunkusumo Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • HIV patient with immunological non-responder status which defined as:
  • first line antiretroviral therapy (ART) treated for minimal 6 months
  • CD4+ level between 200-410 cell/μL
  • HIV viral load <34 copies/mL
  • giving consent to participate the study

Exclusion Criteria:

  • being pregnant
  • lactating
  • known Lactobacillus allergy
  • BMI <16 kg/m2
  • under Tuberculosis treatment or other acute illness
  • acute diarrhea
  • routinely taking selenium containing vitamin in last 1 month
  • routinely consuming probiotics containing product in last 1 month

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: 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.
Other Names:
  • Rillus® Treatment group
Placebo Comparator: 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
Other: 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.
Other Names:
  • Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CD4+ Level
Time Frame: 12 weeks
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.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Th17 Level Change
Time Frame: 12 weeks
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.
12 weeks
16S Ribosomal RNA (rRNA) Total
Time Frame: 12 weeks
Total of 16SrRNA of translocated gut bacteria in blood, measured in copies/mL, presented as median and interquartile range.
12 weeks
Fecal Calprotectin Level Change
Time Frame: 12 weeks

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
12 weeks
Amount of Participants With HIV Related Symptoms
Time Frame: 0,4,8,12 weeks

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.
0,4,8,12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Food Frequency
Time Frame: 0,4, 8, 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.
0,4, 8, 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indonesia University

Investigators

  • Principal Investigator: Erni J Nelwan, MD, PhD, Indonesia University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2018

Primary Completion (Actual)

December 27, 2018

Study Completion (Actual)

December 27, 2018

Study Registration Dates

First Submitted

May 14, 2018

First Submitted That Met QC Criteria

June 22, 2018

First Posted (Actual)

June 26, 2018

Study Record Updates

Last Update Posted (Actual)

May 4, 2025

Last Update Submitted That Met QC Criteria

May 2, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-10-1001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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