VIH-1 Colo-rectal Transmission by Infected Semen Cells and Effects of Seminal Plasma ex Vivo (CellspermVIH) (CellspermVIH)

VIH-1 Colo-rectal Transmission by Infected Semen Cells and Effects of Seminal Plasma ex Vivo

The objective of our project is to determine the infected seminal cell types and the molecular mechanisms involved in HIV cell-associated transmission in the colo-rectal mucosa, using conditions as close as possible to real life, i.e. seminal leukocytes and seminal plasma from HIV-infected donors and tissue explants

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Other: blood sample; Other: sperm sample

Detailed Description

This project relies on:

• our expertise of HIV in semen and male genital tract and our experience in organotypic cultures;
• a network of infectious diseases and reproductive biology clinicians to collect, analyze and process seminal cells and seminal plasma from HIV+ donors;
• the expertise in confocal microscopy and ex vivo colo-rectal model. State of the art culture of colo-rectal tissues, primary cell culture and infection, confocal microscopy, flow cytometry, Polymerase Chain Reaction and Luminex assays for cytokine measurements will be the methodologies primarily used in this project.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Louis Bujan, Pr; Phone Number: 33 05 61 77 10 46; Email: bujan.l@chu-toulouse.fr

Study Locations

• France
  • Paris, France, 75018
    • CECOS Paris Bichat
  • Bretagne
    • Rennes, Bretagne, France, 35200
      • CECOS Bretagne Rennes
  • Midi-Pyrénées
    • Toulouse, Midi-Pyrénées, France, 31059
      • CECOS Hôpital Paule de Viguier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• HIV-1 infected patients who have never been treated by antiretroviral therapy
• Signature of informed consent
• Affiliation to social service

Exclusion Criteria:

• Patients' general condition not allowing protocol follow-up
• Patients with an ejaculation disorder
• Patients unable to perform semen sampling
• Patients with chemotherapy or radiotherapy antecedents
• Patients with very severe oligospermia (≤1million/mL of spermatozoa)
• Patients with active genital infection
• Protected subjects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: HIV-1 infected patients; Blood sample and sperm sample are collected	Other: blood sample; A sample of HIV-1 infected patients's blood is collected; Other: sperm sample; A sample of HIV-1 infected patients's sperm is collected

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize seminal HIV infected cells.	Macrophages and CD4+ T lymphocytes characterization.	1 years
Evaluate the potential of seminal HIV infected cells migration and adhesion.	Assess the potential of seminal macrophages and CD4 T cells to adhere and transmigrate.	1 years
Determine the efficiency of seminal cell associated infection.	The efficiency of seminal cell associated infection will be determinated in the colo-rectal explants.	1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify molecules expressed and involved in seminal cell adhesion and transmigration.	Identify key adhesion molecules expressed by seminal leucocytes and epithelial cells involved in seminal cell adhesion/transmigration.	1 years
Identify seminal and mucosal molecules mediating seminal cell translocation.	Seminal and mucosal soluble molecules mediating seminal cell translocation will be characterized (passive diffusion or active transmigration).	1 years
Determine the impact of seminal plasma/cells exposure on mucosal immune cell.	Mucosal immune cell activation, trafficking and the factors involved, will be evaluated.	1 years

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; ANRS, Emerging Infectious Diseases
• Investigators: Study Director: Nathalie Dejucq-Rainsford, PhD, IRSET

Publications and helpful links

General Publications

• Anderson DJ, Politch JA, Nadolski AM, Blaskewicz CD, Pudney J, Mayer KH. Targeting Trojan Horse leukocytes for HIV prevention. AIDS. 2010 Jan 16;24(2):163-87. doi: 10.1097/QAD.0b013e32833424c8. No abstract available.
• Roulet V, Satie AP, Ruffault A, Le Tortorec A, Denis H, Guist'hau O, Patard JJ, Rioux-Leclerq N, Gicquel J, Jegou B, Dejucq-Rainsford N. Susceptibility of human testis to human immunodeficiency virus-1 infection in situ and in vitro. Am J Pathol. 2006 Dec;169(6):2094-103. doi: 10.2353/ajpath.2006.060191.
• Le Tortorec A, Le Grand R, Denis H, Satie AP, Mannioui K, Roques P, Maillard A, Daniels S, Jegou B, Dejucq-Rainsford N. Infection of semen-producing organs by SIV during the acute and chronic stages of the disease. PLoS One. 2008 Mar 12;3(3):e1792. doi: 10.1371/journal.pone.0001792.
• Le Tortorec A, Satie AP, Denis H, Rioux-Leclercq N, Havard L, Ruffault A, Jegou B, Dejucq-Rainsford N. Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex vivo. Retrovirology. 2008 Dec 31;5:119. doi: 10.1186/1742-4690-5-119.
• Houzet L, Matusali G, Dejucq-Rainsford N. Origins of HIV-infected leukocytes and virions in semen. J Infect Dis. 2014 Dec 15;210 Suppl 3:S622-30. doi: 10.1093/infdis/jiu328.
• Camus C, Matusali G, Bourry O, Mahe D, Aubry F, Bujan L, Pasquier C, Massip P, Ravel C, Zirafi O, Munch J, Roan NR, Pineau C, Dejucq-Rainsford N. Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection. AIDS. 2016 May 15;30(8):1197-208. doi: 10.1097/QAD.0000000000001048.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2017
• Primary Completion (Actual): June 14, 2021
• Study Completion (Actual): June 14, 2021

Study Registration Dates

• First Submitted: March 3, 2017
• First Submitted That Met QC Criteria: March 3, 2017
• First Posted (Actual): March 9, 2017

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: HIV-1; seminal plasma; Colo-rectal transmission
• Other Study ID Numbers: RC31/16/8193; 2016-A01025-46 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The duplicated part of the CRFs will then be sent to Mrs DEJUC at the IRST in Rennes, the remaining part will be kept in the investigating center.

All the data of the study transcribed by the investigator in the CRFs will be transmitted electronically to the person in charge of the data of the INSERM / IRSET 1085 unit. Upon receipt, the data will be entered simply by typing and re-reading on the Excel spreadsheet. The files will be locked by password and backed up daily with storage for 3 months on the server of the INSERM 1085 unit managed by the IT department of the University of Rennes 1. The set Data is saved every evening, with storage for 4 weeks, then archived monthly on tape.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No