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Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy
Auteur(s) : Matusali, G Dereuddre Bosquet, N Le Tortorec, A Moreau, M Satie, A-P Mahé, D Roumaud, P Bourry, O
Auteurs secondaires : Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184) ; Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris-Sud - Paris 11 (UP11) - Commissariat à l'énergie atomique et aux énergies alternatives (CEA) Service de Pharmacologie et Immunoanalyse (SPI) ; Institut de Biologie et Technologies de Saclay We thank Claire Torres (CEA, Division of Immuno-Virology, Fontenay aux Roses, France) for technical assistance with virus quantification. Wealso thank all the technical staff of IDMIT Center, Fontenay-aux-Roses, France. We thank Christophe Joubert, the veterinary surgeon, and thestaff responsible for animal care (CEA, MIRCEN) and assistance in HAART management. The authors declare they have no conflicts of interest.

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
A number of men receiving prolonged suppressive HAART still shed HIV in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with SIVmac251 submitted to HAART for 4 months, intensified over the last seven weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen, or in testis, epididymis, seminal vesicles and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens, and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of non-productively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organs infection in long term treated infected individuals. A substantial subset of men receiving prolonged suppressive HAART in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV-infected macaques treated by HAART. We demonstrated that persistent seminal shedding was not linked to poor drug penetration in semen or semen-producing prostate, seminal vesicle, epididymis and testis. We revealed that HAART decreased SIV RNA to various extents in all male genital organs, with the exception of the urethra, in which SIV RNA+ macrophages were observed despite HAART. Importantly also, HAART did not impact SIV DNA levels in the male genital organs. These results suggest that infection of male genital organs, and particularly the urethra, could be involved in the release of virus in semen during HAART.
ISSN: 0022-538X

hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/file/Detection%20of%20SIV%20in%20Semen%2C%20Urethra%2C%20and%20Male%20Reproductive%20Organs%20during%20Efficient%20Highly%20Active%20Antiretroviral%20Therapy.pdf
PUBMEDCENTRAL : PMC4442442

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