HIV-1 Infection
Conditions
Keywords
HIV, microbial translocation, immune activation, probiotics
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.
Interventions
DIETARY_SUPPLEMENTMulti-strain probiotic
The product consists of Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 added to fermented skimmed milk
DIETARY_SUPPLEMENTPlacebo
Fermented and subsequently heat-treated, sterile skimmed milk
Sponsors
Karolinska University Hospital
Tine
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
Norway, Sweden
Outcome results
None listed