Clinical trial NCT03075397: VIH-1 Colo-rectal Transmission by Infected Semen Cells and Effects of Seminal Plasma ex Vivo (CellspermVIH)
Official title: VIH-1 Colo-rectal Transmission by Infected Semen Cells and Effects of Seminal Plasma ex Vivo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV-1-infection
Keywords: HIV-1
Colo-rectal transmission
seminal plasma
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: ANRS, Emerging Infectious Diseases
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2017-03-09
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Characterize seminal HIV infected cells.
timeFrame: 1 years
measure: Evaluate the potential of seminal HIV infected cells migration and adhesion.
timeFrame: 1 years
measure: Determine the efficiency of seminal cell associated infection.
timeFrame: 1 years
Secondary outcomes:
measure: Identify molecules expressed and involved in seminal cell adhesion and transmigration.
timeFrame: 1 years
measure: Identify seminal and mucosal molecules mediating seminal cell translocation.
timeFrame: 1 years
measure: Determine the impact of seminal plasma/cells exposure on mucosal immune cell.
timeFrame: 1 years
Other outcomes:
Locations:
city: Rennes
country: France
facility: CECOS Bretagne Rennes
state: Bretagne
city: Toulouse
country: France
facility: CECOS Hôpital Paule de Viguier
state: Midi-Pyrénées
city: Paris
country: France
facility: CECOS Paris Bichat
Study officials:
affiliation: IRSET
name: Nathalie Dejucq-Rainsford, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.