Clinical trial NCT03568812: The Role of Probiotics in HIV Patients With Immunological Non-Responder
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Immunological Abnormality
Keywords: HIV
immunological non responder
gut inflammation
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2018-06-26
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind placebo control study
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: CD4+ Level
timeFrame: 12 weeks
Secondary outcomes:
measure: Th17 Level Change
timeFrame: 12 weeks
measure: 16S Ribosomal RNA (rRNA) Total
timeFrame: 12 weeks
measure: Fecal Calprotectin Level Change
timeFrame: 12 weeks
measure: Amount of Participants With HIV Related Symptoms
timeFrame: 0,4,8,12 weeks
Other outcomes:
measure: Change in Food Frequency
timeFrame: 0,4, 8, 12 weeks
Locations:
city: Jakarta
country: Indonesia
facility: HIV Clinic, Cipto Mangunkusumo Hospital
Study officials:
affiliation: Indonesia University
name: Erni J Nelwan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: