Clinical trial NCT04099433: Application of Oral Bacteriotherapy to Promote Anal HPV Clearance in HIV Positive Individuals
Official title: HPVinHIV: Study of Anal HPV Infection in the Setting of HIV Infected Individuals
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV
Anal Dysplasia
Keywords: HIV
HPV
Probiotics
High Resolution Anoscopy
Anal dysplasia
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2019-09-23
Enrollment: 40
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: Published studies suggest that oral probiotic intake can promote the clearance of HPV genital infection and HPV related genital dysplasia in HIV negative women. In the present randomized, double blind, placebo controlled study, investigators will evaluate the ability of oral bacterio-therapy to enhance the clearance of anal HPV infection and anal HPV related dysplasia in HIV infected subjects.

Participants will be evaluated for anal HPV infection and anal dysplasia before and after a 6 months course of daily investigational product intake (Viviomixx® or placebo). HPV infection rate and presence of dysplasia at baseline and at the end of the study will be compared.

Detailed description: Squamous Cell Carcinoma (SCC) of the anus and the anal canal represents a major concern for the HIV infected population, with incidence rates in the different sub populations (women, men, MSM) that are grater than those observed for other common neoplasms in the same HIV negative sub-populations. Nowadays, screening for anal precancerous dysplasia has been included in most national and international HIV management guidelines; in particular, italian guidelines suggest to screen for the presence of HPV related dysplasia:

* HIV+ MSM
* All individuals with previous or current evidence of ant-genital condyloma
* Women with cytology abnormalities on cervical Pap-smear Since no direct anti-HPV drug is currently available and control or clearance of the infection is possible only trough the effect of immune response, interest is addressed to find strategies to promote spontaneous clearance of infection.

In published studies, oral bacterio-therapy demonstrated the ability to promote HPV clearance and HPV related dysplasia regression in HIV negative women.

In the present randomized, double blind, placebo controlled trial, 40 HIV infected individuals with HPV related anal dysplasia will be enrolled.

At baseline participants will undergo:

* anal HPV research and identification
* anal cytology
* anal brushing for evaluation of local inflammatory milieu and microbiota

Subjects with identified HPV anal infection and anal dysplasia will undergo High Resolution Anoscopy (HRA).

During HRA, extra biopsies of identified abnormal areas and biopsies of normal mucosa will be obtained. Extra biopsies will be used to investigate the distribution of intra-epithelial immune cells populations.

Participants will then undergo 6 months of oral supplementation with probiotics (Vivomixx®) or placebo.

At the end of the supplementation period (Vivomixx or placebo), participants will undergo:

* anal HPV research and identification
* anal cytology
* anal brushing for evaluation of local inflammatory milieu and microbiota
* HRA

During HRA, extra biopsies of identified abnormal areas and biopsies of normal mucosa will be obtained. Extra biopsies will be used to investigate the distribution of intra-epithelial immune cells populations.

Eligibility criteria: Inclusion Criteria:

* HIV infected individuals \>18 years old
* stable and effective antiretroviral therapy since at least 12 months
* HPV associated anal dysplasia
* patient willing to provide written informed consent

Exclusion Criteria:

* impossibility to intake the investigational product
* any contraindication to blood sampling
* inflammatory bowel disease
* use of antibiotics during the 3 months prior to the enrollment in the study
* pregnancy

Primary outcomes:
measure: Change from baseline in the number of HPV positive anal swabs
timeFrame: Anal swabs for HPV detection and genotyping will be performed at baseline and after the 6 months duration of the intervention
measure: Change from baseline in the number of dysplastic lesions
timeFrame: Areas of the anal canal that were biopsied at baseline and whom histology showed the presence of dysplasia will undergo a second biopsy after the 6 months duration of the intervention
Secondary outcomes:
measure: Rate of adverse events
timeFrame: This measure will be assessed after the 6 months duration of the intervention
measure: Comparison between intra-epithelial NK lymphocytes subpopulation in normal mucosa and dysplastic mucosa
timeFrame: Biopsies and intra-epithelial lymphocytes extraction will be performed at baseline and after the 6 months duration of the intervention
measure: Comparison between intra-epithelial CD4+ T lymphocytes subpopulation in normal mucosa and dysplastic mucosa
timeFrame: Biopsies and intra-epithelial lymphocytes extraction will be performed at baseline and after the 6 months duration of the intervention
measure: Comparison between intra-epithelial CD8+ T lymphocytes subpopulation in normal mucosa and dysplastic mucosa
timeFrame: Biopsies and intra-epithelial lymphocytes extraction will be performed at baseline and after the 6 months duration of the intervention
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Department of Pubblic Health and Infectious Diseases, "Sapienza" University of Rome
state: RM
Study officials:
References: