Probiotic Supplementation for Those Immune Non-responders With HIV-1 Infection

Gut bacterial community diversity and composition, immune recovery and activation in peripheral plasma/mucosa, plasma levels of gut damage, microbial translocation and inflammation at baseline and after 6 months of receiving intervention will be analyzed.

Up to 25% of HIV-infected individuals receiving antiretroviral treatment demonstrate suboptimal blood cluster of differentiation 4（CD4） recovery despite effective viral suppression; this "immunologic non-responder" (INR) phenotype is associated with increased immune activation and with higher rates of AIDS and non-AIDS related conditions, and death. Poor gut integrity, increased microbial translocation, and reduced CD4 T-cell trafficking to the gut could be a source of ongoing inflammation in INR individuals. Researches have shown that the gut microbiota compositions are different in INRs and immunological responders (IRs). Probiotics, by modulation of gut microbiota, can help induce epithelial healing and prevent bacterial translocation. Probiotic supplementation, therefore, may be a nutritional target for INRs by boosting CD4 cell counts. We design a prospective, case-control, self-contrast study to explore the efficacy and safety of probiotic supplementation in INRs. Participants will receive oral probiotic containing 3 billion Bifidobacterium and 1 billion Lactobacillus once daily. Gut bacterial community diversity and composition, immune recovery and activation in peripheral plasma/mucosa, plasma levels of gut damage, microbial translocation and inflammation at baseline and after 6 months of receiving intervention will be analyzed.

Participants will receive oral probiotic capsules containing 3 billion Bifidobacterium and 1 billion Lactobacillus once daily for 6 months.

Bifidobacteria and Lactobacilli triple viable capsules (provided by Shenzhen Wan he Pharmaceutical Co., Ltd., China) are bilayer mini pellets and are resistant to gastric acid. So Bifidobacterium billion Lactobacillus can only be released in intestine. Participants will take 1.27g (contain 3 billion Bifidobacterium and 1 billion Lactobacillus) once daily.

CD4+ T-cell and cluster of differentiation 8（CD8）+ T-cell counts, CD4/CD8 ratio, cluster of differentiation 38（CD38）+/ human leukocyte antigen(HLA）-HLA class II(DR)+ CD8+/CD4+ T cell ratio

interleukin(IL)-8, IL-1β, IL-6, tumor necrosis factor(TNF)-α, C reactive protein(CRP), D-dimer, Intestinal fatty aid binding protein(I-FABP), lipopolysaccharide(LPS) , lipopolysaccharide-binding protein(LBP), sCD14, sCD40L, and Kynurenine/Tryptophan ratio

Bacterial community diversity and composition determined by 16S ribosomal ribonucleic acid(rRNA) gene sequencing of fecal samples

Inclusion Criteria: Documented HIV-1 infection 18-65 years old On antiretroviral therapy (>2 years) Ability to provide informed consent Undetectable plasma HIV-1 viral load for the past 2 years CD4 T-cell count <350/mm3 for the last 2 years No history of gastrointestinal diseases Exclusion Criteria: Administration of antibiotics, probiotics, or prebiotics or experience of diarrhea within the previous 3 months; Administration of anti-inflammatory drugs, corticosteroids, immunosuppressive drugs, immunomodulator within the previous 3 months; Severe organ dysfunction Pregnancy or breastfeeding