Clinical trial NCT01439841: The Effect of Probiotics in HIV-1 Infection
Official title: The Effect of Probiotics on Microbial Translocation and Immune Activation in HIV-1 Infection. A Randomised Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV-1 Infection
Keywords: HIV
microbial translocation
immune activation
probiotics
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska University Hospital
name: Tine
First posted: 2011-09-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety
timeFrame: 2 months
measure: Changes in measures of microbial translocation
timeFrame: 2 months
measure: Changes in markers of immune activation
timeFrame: 2 months
Secondary outcomes:
measure: Disease progression in untreated patients
timeFrame: 2 months
measure: Immune reconstitution in ART treated patients
timeFrame: 2 months
measure: Gut microbiota composition
timeFrame: 2 months
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
Study officials:
affiliation: Oslo University Hospital
name: Geir Gokstad, MD, PhD
role: STUDY_DIRECTOR
affiliation: Oslo University Hospital
name: Marius Trøseid, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stiksrud B, Nowak P, Nwosu FC, Kvale D, Thalme A, Sonnerborg A, Ueland PM, Holm K, Birkeland SE, Dahm AE, Sandset PM, Rudi K, Hov JR, Dyrhol-Riise AM, Troseid M. Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART. J Acquir Immune Defic Syndr. 2015 Dec 1;70(4):329-37. doi: 10.1097/QAI.0000000000000784.