The Role of Probiotics in HIV Patients With Immunological Non-Responder
Condition: HIV Infections; Immunological Abnormality
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Rillus®; Placebo
Intervention type(s): Drug; Other
Intervention description(s): 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.; 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 intervention name(s): Rillus® Treatment group; Control group
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: double blind placebo control study
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: HIV; immunological non responder; gut inflammation