The Effect of Probiotics in HIV-1 Infection (ProGut)

University of Oslo (UIO)

Status: Completed

Conditions: HIV-1 Infection

Treatments: Dietary Supplement: Placebo; Dietary Supplement: Multi-strain probiotic

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01439841

ProGut1.0

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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32 participants in 3 patient groups, including a placebo group

Probiotics

Experimental group

Description:

A multi-strain Probiotic consisting of Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 added to fermented skimmed milk (Biola®, TINE SA, Oslo), 250 mL/day for 8 weeks.

Treatment:

Dietary Supplement: Multi-strain probiotic

Placebo

Placebo Comparator group

Description:

Fermented and subsequently heat-treated, sterile skimmed milk (TINE SA) as active placebo.

Treatment:

Dietary Supplement: Placebo

Control

No Intervention group

Description:

No intervention