The Effect of Probiotics in HIV-1 Infection
- Conditions
- HIV-1 Infection
- Registration Number
- NCT01439841
- Lead Sponsor
- Oslo University Hospital
- Brief Summary
HIV progression is closely associated with chronic immune activation driven by leakage of bacterial products from a damaged gut, the investigators largest immunological organ. Notably, the degree of immune activation has been suggested to be a better predictor of disease progression than plasma viral load, and markers of immune activation and gut damage have been identified as therapeutic targets per se. The major damage by HIV to the immune system is an initial massacre of gut mucosal CD4+ Th17 cells. Interestingly, a normal gut flora has been shown to induce the maturation of Th17 cells in the small intestine mucosa. Preliminary reports have shown that the gut flora is altered in HIV-1 infection compared to controls. In this project, the investigators will characterize microbial composition of gut flora in chronic HIV infection with ultradeep sequencing. Gut flora composition will be related to clinical data as well as quantitative data of circulating microbial products and activation markers. Second, in a randomized clinical trial (RCT) the effect of probiotic lactobacilli on HIV pathogenesis and progression will be tested. This Gram-positive strain is clinically tested and is able to colonize the gut.
- Detailed Description
Objectives:
To explore (i) the safety and tolerability, and (ii) the efficacy of probiotics on HIV-associated microbial translocation, systemic immune activation, disease progression and composition of gut microbiota in chronic HIV-1 infection.
Methodology/Study design:
Approximately 50 patients without current indication for antiretroviral treatment (ART) and 50 patients receiving ART without normalised CD4 counts will be included. A controlled clinical trial will be carried out within each stratum randomised in a 2:1:1 fashion to double blinded intervention and placebo arms as well as an open, untreated control arm, respectively.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- For patients without ART: Confirmed diagnosis of HIV infection > 6 months and CD4+ T cell count < 900
- For patients on stable, effective ART: HIV RNA < 50 copies/ml > 6 months and CD4+ T cell count > 500
- Signed informed consent.
- Severe illness requiring hospitalization
- Systemic antibiotics or probiotics the last two months
- Current immune modulating therapy
- Infectious diarrhea
- Inflammatory bowel disease
- Acute primary HIV infection
- Patients immigrating from Africa, Asia or Latin-America within the last 6 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Safety 2 months Adverse events monitoring during the study period of 2 months
Changes in measures of microbial translocation 2 months Changes in plasma leves of lipopolysaccharide (LPS) and soluble CD14 from baseline to 2 months (end of study)
Changes in markers of immune activation 2 months Changes in CD38, HLA-DR and PD-1 on CD8+ and CD4+ T cells from baseline to 2 months (end of study)
- Secondary Outcome Measures
Name Time Method Disease progression in untreated patients 2 months Changes in CD4 count, viral load, clinical events and indication for ART from baseline to 2 months (end of study)
Immune reconstitution in ART treated patients 2 months Changes in CD4 count from baseline to 2 months (end of study)
Gut microbiota composition 2 months Changes in gut microbiota (454 pyrosequencing of fecal samples) from baseline to 2 months (end of study)
Trial Locations
- Locations (2)
Oslo University Hospital
🇳🇴Oslo, Norway
Karolinska University Hospital Huddinge
🇸🇪Stockholm, Sweden
Oslo University Hospital🇳🇴Oslo, Norway