Clinical trial NCT02640625: Improving Prognosis in HIV Infection
Official title: Adjuvant Mucosal Therapy in HIV-infected Men With Insufficient Response to Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Human Immunodeficiency Virus
Keywords: HIV
Probiotics
Microbiota
Mucosal immunology
Gut biopsy
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: University of Oslo
First posted: 2015-12-29
Enrollment: 20
Sex: MALE
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the safety of probiotics in cART-treated immunologic non-responder (INR) patients with chronic HIV infection.

The secondary objectives are to i) explore the biological effects of probiotics in combined antiretroviral therapy(cART)-treated INR patient with chronic HIV infection, and ii) investigate differences between cART-treated HIV-infected INR and non-INR patients with regards to gut microbial composition and mucosal barrier function.


Eligibility criteria: Inclusion Criteria:

* HIV seropositive \>4 years.
* Continuous combined antiretroviral treatment (cART) \>4 years.
* Plasma HIV RNA \<50 copies/mL \>3,5 years.
* Cluster of differentiation(CD)4+ T cell count \<400 cells/µL (OR \>600 cells/µl) \>3.5 years.
* Caucasian
* Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Committee on Harmonization (ICH) Good Clinical Practice (GCP), and national/local regulations.

Exclusion Criteria:

* Plasma hepatitis C (HCV) RNA positive.
* Serum hepatitis B surface antigen (HBsAg) positive.
* Comorbidity of inflammatory bowel disease, coeliac disease or malnutrition.
* Concomitant use of non-steroid anti-inflammatory drugs (NSAID), corticosteroids, disease-modifying antirheumatic drugs, or other anti-inflammatory pharmaceutical substances.
* Concomitant use of antithrombotic pharmaceutical substances
* Regular (weekly) use of any probiotic substance within 3 months prior to inclusion.
* Use of antibiotics within 3 months prior to inclusion.
* Deranged liver function (serum albumin \<25 g/L or Child-Pugh ≥10)
* Renal failure (estimated glomerular filtration rate (eGFR) \<30 ml/min)
* Heart failure (NYHA class II-IV)
* Intolerance to milk or phenylalanine
* Any reason why, in the opinion of the investigator, the patient should not participate

Primary outcomes:
measure: Adverse Effects
timeFrame: 10 weeks
measure: Delta HIV Viral Load
timeFrame: 8 weeks
measure: Delta Blood CD4 Count
timeFrame: 8 weeks
Secondary outcomes:
measure: Alteration in Gut Microbiota Composition
timeFrame: 8 weeks
measure: Alterations in Epithelial Gene Expression
timeFrame: 8 weeks
measure: Alterations in Lamina Propria T Cell Subsets
timeFrame: 8 weeks
measure: Alterations in Systemic T Cell Intracellular Signaling
timeFrame: 8 weeks
measure: Alterations in Systemic Markers of Immune Activation
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital (Ullevaal campus)
Study officials:
affiliation: Oslo University Hospital
name: Dag Henrik Reikvam, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meyer-Myklestad MH, Medhus AW, Stiksrud B, Lorvik KB, Seljeflot I, Hansen SH, Holm K, Hov JR, Kvale D, Dyrhol-Riise AM, Kummen M, Troseid M, Reikvam DH. Probiotics to HIV-Infected Immunological Nonresponders: Altered Mucosal Immunity and Microbial Diversity Restricted to Ileum. J Acquir Immune Defic Syndr. 2022 Jan 1;89(1):77-86. doi: 10.1097/QAI.0000000000002817.