InHIV type 1-infected children cytotoxic T lymphocyte responses are associated with greater reduction of viremia under antiretroviral therapy

被引:8
作者
Buseyne, F
Le Chenadec, J
Burgard, M
Bellal, N
Mayaux, MJ
Rouzioux, C
Rivière, Y
Blanche, S
机构
[1] Inst Pasteur, CNRS, URA 1930, Unite Postulante Immunopathol Virale, F-75015 Paris, France
[2] Hop Kremlin Bicetre, INSERM, U569, F-94276 Le Kremlin Bicetre, France
[3] Univ Paris 05, CHU Necker Enfants Malad, Virol Lab, F-75015 Paris, France
[4] CHU Necker Enfants Malad, Federat Pediat, F-75015 Paris, France
关键词
D O I
10.1089/aid.2005.21.719
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The evolution of the HIV-specific CD8(+) T cell response in patients receiving potent combination therapy has been well documented in adult patients. However, no study reported whether baseline HIV-specific CD8(+) T cell response is linked to treatment outcome. The aims of this study were to investigate both the impact of baseline memory cytotoxic T lymphocytes (CTL) on treatment outcome and the effect of potent therapy on memory HIV-specific CTL in HIV-1-infected pediatric patients. The study group comprised 30 children who started a first-line combination treatment including at least three drugs from two different classes and were longitudinally followed during treatment. Their memory HIV-specific responses were measured at baseline and during treatment, as well as their plasma viremia and CD4(+) levels. The intensity of memory Gag-specific CTL and the breadth of the CTL response at the beginning of treatment were significantly correlated with lower plasma viral load during treatment, independently of baseline plasma viral load, CD4(+) counts, and age. Children with partially controlled viral replication had enhanced Gag-specific CTL compared to their baseline value. This improvement of antiviral responses during treatment was not observed when viral replication was either fully suppressed or uncontrolled. In conclusion, our results show that higher baseline HIV-specific CTL are linked to lower viremia under combination therapy. This result adds further support to the hypothesis that cooperation between the antiviral immune response and antiviral drugs could be helpful for therapeutic management of HIV-infected patients.
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页码:719 / 727
页数:9
相关论文
共 51 条
[1]   Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load [J].
Addo, MM ;
Yu, XG ;
Rathod, A ;
Cohen, D ;
Eldridge, RL ;
Strick, D ;
Johnston, MN ;
Corcoran, C ;
Wurcel, AG ;
Fitzpatrick, CA ;
Feeney, ME ;
Rodriguez, WR ;
Basgoz, N ;
Draenert, R ;
Stone, DR ;
Brander, C ;
Goulder, PJR ;
Rosenberg, ES ;
Altfeld, M ;
Walker, BD .
JOURNAL OF VIROLOGY, 2003, 77 (03) :2081-2092
[2]   Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses:: Relationship to viral load in untreated HIV infection [J].
Betts, MR ;
Ambrozak, DR ;
Douek, DC ;
Bonhoeffer, S ;
Brenchley, JM ;
Casazza, JP ;
Koup, RA ;
Picker, LJ .
JOURNAL OF VIROLOGY, 2001, 75 (24) :11983-11991
[3]   Early HIV-specific cytotoxic T lymphocytes and disease progression in children born to HIV-infected mothers [J].
Buseyne, F ;
Burgard, M ;
Teglas, JP ;
Bui, E ;
Rouzioux, C ;
Mayaux, MJ ;
Blanche, S ;
Rivière, Y .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 1998, 14 (16) :1435-1444
[4]  
BUSEYNE F, 1993, J IMMUNOL, V150, P3569
[5]   Inverse correlation between memory Gag-specific cytotoxic T lymphocytes and viral replication in human immunodeficiency virus-infected children [J].
Buseyne, F ;
Le Chenadec, J ;
Corre, B ;
Porrot, F ;
Burgard, M ;
Rouzioux, C ;
Blanche, S ;
Mayaux, MJ ;
Rivière, Y .
JOURNAL OF INFECTIOUS DISEASES, 2002, 186 (11) :1589-1596
[6]   Frequencies of ex vivo-activated human immunodeficiency virus type 1-specific gamma-interferon-producing CD8+ T cells in infected children correlate positively with plasma viral load [J].
Buseyne, F ;
Scott-Algara, D ;
Porrot, F ;
Corre, B ;
Bellal, N ;
Burgard, M ;
Rouzioux, C ;
Blanche, S ;
Rivière, Y .
JOURNAL OF VIROLOGY, 2002, 76 (24) :12414-12422
[7]   Cross-clade-specific cytotoxic T lymphocytes in HIV-1-infected children [J].
Buseyne, F ;
Chaix, ML ;
Fleury, B ;
Manigard, O ;
Burgard, M ;
Blanche, S ;
Rouzioux, C ;
Rivière, Y .
VIROLOGY, 1998, 250 (02) :316-324
[8]   Comprehensive analysis of human immunodeficiency virus type 1 (HIV71)-specific gamma interferon-secreting CD8+ T cells in primary HIV-1 infection [J].
Cao, JH ;
McNevin, J ;
Holte, S ;
Fink, L ;
Corey, L ;
McElrath, AJ .
JOURNAL OF VIROLOGY, 2003, 77 (12) :6867-6878
[9]   Determinants of HIV-specific CD8 T-cell responses in HIV-infected pediatric patients and enhancement of HIV-gag-specific responses with exogenous IL-15 [J].
Chitnis, V ;
Pahwa, R ;
Pahwa, S .
CLINICAL IMMUNOLOGY, 2003, 107 (01) :36-45
[10]   Thymic volume predicts long-term immune reconstitution in HIV-infected children treated with highly active antiretroviral therapy [J].
Clerici, M ;
Saresella, M ;
Trabattoni, D ;
Ferrante, P ;
Vanzulli, A ;
Vigano, A .
AIDS, 2002, 16 (16) :2219-2221