Factors influencing peripheral blood mononuclear cell-associated HIV-1 DNA level after long-term suppressive antiretroviral therapy in 236 patients

被引:32
作者
Burgard, Marianne [1 ]
Boufassa, Faroudy [2 ]
Viard, Jean-Paul [3 ,4 ]
Garrigue, Isabelle [5 ]
Ruffault, Annick [6 ]
Izopet, Jacques [7 ]
Vabret, Astrid [8 ]
Descamps, Diane [9 ]
Colson, Philippe [10 ]
Seigneurin, Jean-Marie [11 ]
Rouzioux, Christine [1 ,4 ]
机构
[1] CHU Necker Enfants Malad, Virol Lab, AP HP, F-75015 Paris, France
[2] Univ Paris Sud, Hop Bicetre, INSERM, Dept Epidemiol,U822, F-94275 Le Kremlin Bicetre, France
[3] CHU Necker Enfants Malad, Serv Malad Infect, AP HP, F-75015 Paris, France
[4] Univ Paris 05, EA 3620, Paris, France
[5] CHU Bordeaux, Virol Lab, Bordeaux, France
[6] CHU Rennes, Virol Lab, Rennes, France
[7] CHU Toulouse, Virol Lab, Toulouse, France
[8] CHU Caen, Virol Lab, F-14000 Caen, France
[9] CHU Bichat, Virol Lab, AP HP, Paris, France
[10] CHU Marseille, Federat Microbiol Clin, Marseille, France
[11] CHU Grenoble, Virol Lab, F-38043 Grenoble, France
关键词
antiretroviral therapy; HIV-1; DNA; long-term therapy; suppressive therapy; viral load; CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; DISEASE PROGRESSION; LIFELONG PERSISTENCE; LATENT INFECTION; EXTENDED PERIODS; VIRAL LOAD; RESERVOIR; QUANTIFICATION; STABILITY;
D O I
10.1097/QAD.0b013e32833032d4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: The objectives of this study were to determine whether peripheral blood mononuclear cell (PBMC)-associated HIV-1 DNA level in patients on long-term suppressive antiretroviral therapy (ART) was associated with plasma HIV-1 RNA level, CD4 cell count, and therapeutic factors throughout patient history. Design: Patients receiving triple or dual therapy with plasma HIV-1 RNA below detection limit for more than 3 years were recruited in a multicentric, cross-sectional study within the eight virology laboratories of the Agence Nationale de Recherche sur le SIDA et les Hepatites virales HIV quantification working group, each one in relation with a clinical center. Methods: PBMC-associated HIV-1 DNA was quantified using a standardized real-time PCR method in all laboratories. Results: A total of 236 patients was included. Median HIV-1 DNA was 2.8 log(10) copies/10(6) PBMCs (interquartile range 2.4-3.0). Univariate analysis showed PBMC HIV-1 DNA level to be related to pre-ART immuno-virologic status (plasma HIV-1 RNA zenith and CD4 cell count nadir) and to current CD4(+) T-cell count. HIV-1 DNA was lower in patients receiving ART with inferior virologic efficacy, as they also had a higher CD4 nadir and a lower HIV-1 RNA zenith than other patients. PBMC HIV-1 DNA level was not related to therapy duration, to time spent with undetectable HIV-1 RNA or to occurrence of a blip. Plasma HIV-1 RNA zenith and CD4 cell count nadir remained predictive of HIV-1 DNA level in the multivariate model which was associated with 22% of its variability. Conclusion: Whatever the duration of treatment, HIV-1 DNA level during ART gives a picture of the intensity of viral replication and immune deficiency reached before starting therapy. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
引用
收藏
页码:2165 / 2171
页数:7
相关论文
共 42 条
[1]  
[Anonymous], PRISE CHARGE MED PER
[2]   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
[3]   HIV-1 DNA for the measurement of the HIV reservoir is predictive of disease progression in seroconverters whatever the mode of result expression is [J].
Avettand-Fenoel, Veronique ;
Boufassa, Faroudy ;
Galimand, Julie ;
Meyer, Laurence ;
Rouzioux, Christine .
JOURNAL OF CLINICAL VIROLOGY, 2008, 42 (04) :399-404
[4]   Decay of the HIV reservoir in patients receiving antiretroviral therapy for extended periods: Implications for eradication of virus [J].
Chun, Tae-Wook ;
Justement, J. Shawn ;
Moir, Susan ;
Hallahan, Claire W. ;
Maenza, Janine ;
Mullins, James I. ;
Collier, Ann C. ;
Corey, Lawrence ;
Fauci, Anthony S. .
JOURNAL OF INFECTIOUS DISEASES, 2007, 195 (12) :1762-1764
[5]   HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir [J].
Chun, TW ;
Nickle, DC ;
Justement, JS ;
Large, D ;
Semerjian, A ;
Curlin, ME ;
O'Shea, MA ;
Hallahan, CW ;
Daucher, M ;
Ward, DJ ;
Moir, S ;
Mullins, JI ;
Kovacs, C ;
Fauci, AS .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (11) :3250-3255
[6]   Quantification of latent tissue reservoirs and total body viral load in HIV-1 Infection [J].
Chun, TW ;
Carruth, L ;
Finzi, D ;
Shen, XF ;
DiGiuseppe, JA ;
Taylor, H ;
Hermankova, M ;
Chadwick, K ;
Margolick, J ;
Quinn, TC ;
Kuo, YH ;
Brookmeyer, R ;
Zeiger, MA ;
BarditchCrovo, P ;
Siliciano, RF .
NATURE, 1997, 387 (6629) :183-188
[7]   Early establishment of a pool of latently infected, resting CD4+ T cells during primary HIV-1 infection [J].
Chun, TW ;
Engel, D ;
Berrey, MM ;
Shea, T ;
Corey, L ;
Fauci, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8869-8873
[8]   Levels of HIV-infected peripheral blood cells remain stable throughout the natural history of HIV-1 infection [J].
Cone, RW ;
Gowland, P ;
Opravil, M ;
Grob, P ;
Ledergerber, B .
AIDS, 1998, 12 (17) :2253-2260
[9]   Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy [J].
Finzi, D ;
Blankson, J ;
Siliciano, JD ;
Margolick, JB ;
Chadwick, K ;
Pierson, T ;
Smith, K ;
Lisziewicz, J ;
Lori, F ;
Flexner, C ;
Quinn, TC ;
Chaisson, RE ;
Rosenberg, E ;
Walker, B ;
Gange, S ;
Gallant, J ;
Siliciano, RF .
NATURE MEDICINE, 1999, 5 (05) :512-517
[10]   CD4 cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients [J].
Goujard, C ;
Bonarek, M ;
Meyer, L ;
Bonnet, F ;
Chaix, ML ;
Deveau, C ;
Sinet, M ;
Galimand, J ;
Delfraissy, JF ;
Venet, A ;
Rouzioux, C ;
Morlat, P .
CLINICAL INFECTIOUS DISEASES, 2006, 42 (05) :709-715