Persistent But Not Replicating HIV-1 Cell-Associated DNA in Semen of Long-Term ART Experienced Men

被引:1
作者
Gagneux-Brunon, Amandine [1 ,2 ]
Nasri, Dorsaf [1 ,3 ]
Terrasse, Rachel [1 ]
Saune, Karine [4 ]
Gagnieu, Marie-Claude [5 ]
Fresard, Anne [2 ]
Delezay, Olivier [1 ]
Izopet, Jacques
Pozzetto, Bruno [1 ,3 ]
Lucht, Frederic [1 ,2 ]
Bourlet, Thomas [1 ,3 ]
机构
[1] Univ Lyon, Univ St Etienne, GIMAP EA3064, CIC1408, St Etienne, France
[2] Ctr Hosp Univ, Serv Malad Infect & Trop, St Etienne, France
[3] Ctr Hosp Univ, Serv Agents Infectieux & Hyg, St Etienne, France
[4] INSERM U1043, Ctr Physiopathol Toulouse Purpan, Toulouse, France
[5] Ctr Hosp Univ Lyon, Lab Pharmacol, Lyon, France
关键词
HIV-1; antiretroviral therapy; genital tract; HIV DNA; semen; viral load; ACTIVE ANTIRETROVIRAL THERAPY; BLOOD MONONUCLEAR-CELLS; VIRAL LOAD; RNA; SEX; TRANSMISSION; INFECTION; DECREASE; IMPACT; HAART;
D O I
10.2174/1570162X14666151118115601
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: The semen of HIV-1 infected men represents the main vector of HIV-1 spread following sexual transmission of cell-free or cell-associated virions. Objective: The present study aimed to assess the impact of HAART on HIV-1 RNA/DNA and on inflammatory environment in the semen of long-term HAART-experienced men. Methods: Forty-five paired samples of semen and blood were obtained from 37 consenting men, 10 untreated and 27 under HAART. Blood and seminal HIV RNA and DNA loads were quantified by the Abbott RealTime m2000rt assay and an in-house real-time PCR protocol, respectively. Tat/rev/nef intra-cellular mRNA was tested by qualitative PCR. Interleukin (IL)-1 beta, IL-2, IL-6, IL-7, IL-8, IL-10, GM-CSF and TNF alpha were quantified in 20 paired samples by Bio-plex (R) assay. Results: No semen was found HIV RNA positive in men under HAART. Twenty-six percent of semen samples from HAART-experienced men remained positive for HIV DNA. Seminal HIV DNA was significantly associated with the duration of infection and the HIV DNA load in blood. No seminal mononuclear cells were found positive for intracellular HIV RNA in HAART experienced men. All the tested chemokines exhibited significantly higher concentration in semen than in blood in both treated and untreated men. No effect of HAART on cytokines/chimiokines loads was observed. Conclusion: These results demonstrate the efficacy of HAART on the reduction of seminal RNA HIV-1 loads despite the persistence of local inflammation. Moreover, in our hands the seminal cell-associated virus reservoir was not reactivated in an inflammatory environment was not productive and its reactivation seems unlikely.
引用
收藏
页码:316 / 323
页数:8
相关论文
共 30 条
[1]   HIV-1 Populations in Semen Arise through Multiple Mechanisms [J].
Anderson, Jeffrey A. ;
Ping, Li-Hua ;
Dibben, Oliver ;
Jabara, Cassandra B. ;
Arney, Leslie ;
Kincer, Laura ;
Tang, Yuyang ;
Hobbs, Marcia ;
Hoffman, Irving ;
Kazembe, Peter ;
Jones, Corbin D. ;
Borrow, Persephone ;
Fiscus, Susan ;
Cohen, Myron S. ;
Swanstrom, Ronald .
PLOS PATHOGENS, 2010, 6 (08) :51-52
[2]   Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis [J].
Attia, Suzanna ;
Egger, Matthias ;
Mueller, Monika ;
Zwahlen, Marcel ;
Low, Nicola .
AIDS, 2009, 23 (11) :1397-1404
[3]  
Barroso PF, 2000, ANN INTERN MED, V133, P280, DOI 10.7326/0003-4819-133-4-200008150-00012
[4]   Evidence for gene expression by unintegrated human immunodeficiency virus type 1 DNA species [J].
Brussel, A ;
Sonigo, P .
JOURNAL OF VIROLOGY, 2004, 78 (20) :11263-11271
[5]   Intermittent human immunodeficiency type 1 virus (HIV-1) shedding in semen and efficiency of sperm processing despite high seminal HIV-1 RNA levels [J].
Bujan, L ;
Daudin, M ;
Alvarez, M ;
Massip, P ;
Puel, J ;
Pasquier, C .
FERTILITY AND STERILITY, 2002, 78 (06) :1321-1323
[6]   Association between HSV-2 and HIV-1 viral load in semen, cervico-vaginal secretions and genital ulcers of Thai men and women [J].
Chu, Kathryn ;
Jiamton, Sukhurn ;
Pepin, Jacques ;
Cowan, Frances ;
Mahakkanukrauh, Bussakorn ;
Suttent, Ruengpung ;
Robinson, Noah J. ;
Deslandes, Sylvie ;
Frost, Eric ;
Chaisilwattana, Pongsakdi ;
Suthipinittharm, Puan ;
Grosskurth, Heiner ;
Brown, David ;
Jaffar, Shabbar .
INTERNATIONAL JOURNAL OF STD & AIDS, 2006, 17 (10) :681-686
[7]   Prevention of HIV-1 Infection with Early Antiretroviral Therapy [J].
Cohen, Myron S. ;
Chen, Ying Q. ;
McCauley, Marybeth ;
Gamble, Theresa ;
Hosseinipour, Mina C. ;
Kumarasamy, Nagalingeswaran ;
Hakim, James G. ;
Kumwenda, Johnstone ;
Grinsztejn, Beatriz ;
Pilotto, Jose H. S. ;
Godbole, Sheela V. ;
Mehendale, Sanjay ;
Chariyalertsak, Suwat ;
Santos, Breno R. ;
Mayer, Kenneth H. ;
Hoffman, Irving F. ;
Eshleman, Susan H. ;
Piwowar-Manning, Estelle ;
Wang, Lei ;
Makhema, Joseph ;
Mills, Lisa A. ;
de Bruyn, Guy ;
Sanne, Ian ;
Eron, Joseph ;
Gallant, Joel ;
Havlir, Diane ;
Swindells, Susan ;
Ribaudo, Heather ;
Elharrar, Vanessa ;
Burns, David ;
Taha, Taha E. ;
Nielsen-Saines, Karin ;
Celentano, David ;
Essex, Max ;
Fleming, Thomas R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (06) :493-505
[8]   Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: Evidence for compartmentalization of HIV-1 between semen and blood [J].
Coombs, RW ;
Speck, CE ;
Hughes, JP ;
Lee, W ;
Sampoleo, R ;
Ross, SO ;
Dragavon, J ;
Peterson, G ;
Hooton, TM ;
Collier, AC ;
Corey, L ;
Koutsky, L ;
Krieger, JN .
JOURNAL OF INFECTIOUS DISEASES, 1998, 177 (02) :320-330
[9]   No detection of HIV 1-RNA in semen of men on efficient HAART in the past 4 years of a 2002-2009 survey [J].
Dulioust, Emmanuel ;
Leruez-Ville, Marianne ;
Guibert, Juliette ;
Fubini, Alessandra ;
Jegou, David ;
Launay, Odile ;
Sogni, Philippe ;
Jouannet, Pierre ;
Rouzioux, Christine .
AIDS, 2010, 24 (10) :1595-1598
[10]   Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male and female genital tract [J].
Else, Laura J. ;
Taylor, Stephen ;
Back, David J. ;
Khoo, Saye H. .
ANTIVIRAL THERAPY, 2011, 16 (08) :1149-1167