Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study

被引:823
作者
Saez-Cirion, Asier [1 ]
Bacchus, Charline [2 ]
Hocqueloux, Laurent [3 ]
Avettand-Fenoel, Veronique [4 ,5 ]
Girault, Isabelle [6 ]
Lecuroux, Camille [6 ]
Potard, Valerie [7 ,8 ]
Versmisse, Pierre [1 ]
Melard, Adeline [4 ]
Prazuck, Thierry [3 ]
Descours, Benjamin [2 ]
Guergnon, Julien [2 ]
Viard, Jean-Paul [5 ,9 ]
Boufassa, Faroudy [10 ]
Lambotte, Olivier [6 ,11 ]
Goujard, Cecile [10 ,11 ]
Meyer, Laurence [10 ,12 ]
Costagliola, Dominique [7 ,8 ,13 ]
Venet, Alain [6 ]
Pancino, Gianfranco [1 ]
Autran, Brigitte [2 ]
Rouzioux, Christine [4 ,5 ]
机构
[1] Inst Pasteur, Unite Regulat Infect Retrovirales, Paris, France
[2] Univ Paris 06, INSERM UMR Immunite & Infect S 945, Hop La Pitie Salpetriere, Paris, France
[3] Ctr Hosp Reg Orleans, Serv Malad Infect & Trop, Orleans, France
[4] CHU Necker Enfants Malad, AP HP, Virol Lab, Paris, France
[5] Univ Paris 05, EA 3620, Paris, France
[6] Univ Paris 11, INSERM U1012, Le Kremlin Bicetre, France
[7] Univ Paris 06, UMR S 943, Paris, France
[8] INSERM, U943, Paris, France
[9] Hop Hotel Dieu, AP HP, Paris, France
[10] Univ Paris 11, INSERM U1018, Le Kremlin Bicetre, France
[11] Hop Bicetre, AP HP, Serv Med Interne, Le Kremlin Bicetre, France
[12] Hop Bicetre, AP HP, Dept Epidemiol, Le Kremlin Bicetre, France
[13] Grp Hosp Pitie Salpetriere, AP HP, Serv Malad Infect & Trop, F-75634 Paris, France
关键词
CD4(+) T-CELLS; VIRAL LOAD; PRIMARY INFECTION; IMMUNE FUNCTION; EX-VIVO; IN-VIVO; VIRUS; REPLICATION; MEMORY; SUPPRESSION;
D O I
10.1371/journal.ppat.1003211
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naive T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.
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页数:12
相关论文
共 47 条
[1]  
Alizadeh M, 2008, TISSUE ANTIGENS, V71, P315
[2]   Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection [J].
Alter, G ;
Teigen, N ;
T Davis, B ;
Addo, MM ;
Suscovich, TJ ;
Waring, MT ;
Streeck, H ;
Johnston, MN ;
Staller, KD ;
Zaman, MT ;
Yu, XG ;
Lichterfeld, M ;
Basgoz, N ;
Rosenberg, ES ;
Altfeld, M .
BLOOD, 2005, 106 (10) :3366-3369
[3]  
Assoumou L, 2010, ANTIVIR THER, V15, pA185
[4]   HIV-DNA in rectal cells is well correlated with HIV-DNA in blood in different groups of patients, including long-term non-progressors [J].
Avettand-Fenoel, Veronique ;
Prazuck, Thierry ;
Hocqueloux, Laurent ;
Melard, Adeline ;
Michau, Christophe ;
Kerdraon, Remy ;
Agoute, Eric ;
Rouzioux, Christine .
AIDS, 2008, 22 (14) :1880-1882
[5]   LTR Real-Time PCR for HIV-1 DNA Quantitation in Blood Cells for Early Diagnosis in Infants Born to Seropositive Mothers Treated in HAART Area (ANRS CO 01) [J].
Avettand-Fenol, Veronique ;
Chaix, Marie-Laure ;
Blanche, Stephane ;
Burgard, Marianne ;
Floch, Corinne ;
Toure, Kadidia ;
Allemon, Marie-Christine ;
Warszawski, Josiane ;
Rouzioux, Christine .
JOURNAL OF MEDICAL VIROLOGY, 2009, 81 (02) :217-223
[6]   CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection [J].
Beaumier, Coreen M. ;
Harris, Levelle D. ;
Goldstein, Simoy ;
Klatt, Nichole R. ;
Whitted, Sonya ;
McGinty, John ;
Apetrei, Cristian ;
Pandrea, Ivona ;
Hirsch, Vanessa M. ;
Brenchley, Jason M. .
NATURE MEDICINE, 2009, 15 (08) :879-U75
[7]   Treatment interruptions in HIV-infected subjects [J].
Bongiovanni, Marco ;
Casana, Maddalena ;
Tincati, Camilla ;
Monforte, Antonella d'Arminio .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 58 (03) :502-505
[8]   CD4 Dynamics over a 15 Year-Period among HIV Controllers Enrolled in the ANRS French Observatory [J].
Boufassa, Faroudy ;
Saez-Cirion, Asier ;
Lechenadec, Jerome ;
Zucman, David ;
Avettand-Fenoel, Veronique ;
Venet, Alain ;
Rouzioux, Christine ;
Delfraissy, Jean-Francois ;
Lambotte, Olivier ;
Meyer, Laurence .
PLOS ONE, 2011, 6 (04)
[9]   T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: Implications for HIV pathogenesis [J].
Brenchley, JM ;
Hill, BJ ;
Ambrozak, DR ;
Price, DA ;
Guenaga, FJ ;
Casazza, JP ;
Kuruppu, J ;
Yazdani, J ;
Migueles, SA ;
Connors, M ;
Roederer, M ;
Douek, DC ;
Koup, RA .
JOURNAL OF VIROLOGY, 2004, 78 (03) :1160-1168
[10]   When to Initiate Combined Antiretroviral Therapy to Reduce Mortality and AIDS-Defining Illness in HIV-Infected Persons in Developed Countries An Observational Study [J].
Cain, Lauren E. ;
Logan, Roger ;
Robins, James M. ;
Sterne, Jonathan A. C. ;
Sabin, Caroline ;
Bansi, Loveleen ;
Justice, Amy ;
Goulet, Joseph ;
van Sighem, Ard ;
de Wolf, Frank ;
Bucher, Heiner C. ;
von Wyl, Viktor ;
Esteve, Anna ;
Casabona, Jordi ;
del Amo, Julia ;
Moreno, Santiago ;
Seng, Remonie ;
Meyer, Laurence ;
Perez-Hoyos, Santiago ;
Muga, Roberto ;
Lodi, Sara ;
Lanoy, Emilie ;
Costagliola, Dominique ;
Hernan, Miguel A. .
ANNALS OF INTERNAL MEDICINE, 2011, 154 (08) :509-515