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
[21]  
PALMER S, 2009, CROI C MONTR FEBR
[22]   Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy [J].
Palmer, Sarah ;
Malclarelli, Frank ;
Wiegand, Ann ;
Bernstein, Barry ;
Hanna, George J. ;
Brun, Scott C. ;
Kempf, Dale J. ;
Mellors, John W. ;
Coffin, John M. ;
King, Martin S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (10) :3879-3884
[23]   Predictive value of provirus load and DNA human immunodeficiency virus genotype for successful abacavir-based simplified therapy [J].
Pellegrin, I ;
Caumont, A ;
Garrigue, I ;
Merel, P ;
Schrive, MH ;
Fleury, H ;
Dupon, M ;
Pellegrin, JL ;
Ragnaud, JM .
JOURNAL OF INFECTIOUS DISEASES, 2003, 187 (01) :38-46
[24]  
PIKETTY C, 2006, 16 INT AIDS C TOR CA
[25]   The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy [J].
Ramratnam, B ;
Mittler, JE ;
Zhang, LQ ;
Boden, D ;
Hurley, A ;
Fang, F ;
Macken, CA ;
Perelson, AS ;
Markowitz, M ;
Ho, DD .
NATURE MEDICINE, 2000, 6 (01) :82-85
[26]   Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection [J].
Robbins, GK ;
De Gruttola, V ;
Shafer, RW ;
Smeaton, LM ;
Snyder, SW ;
Pettinelli, C ;
Dube, MP ;
Fischl, MA ;
Pollard, RB ;
Delapenha, R ;
Gedeon, L ;
van der Horst, C ;
Murphy, RL ;
Becker, MI ;
D'Aquila, RT ;
Vella, S ;
Merigan, TC ;
Hirsch, MS ;
Nokta, M ;
Johnson, V ;
Morse, G ;
Putnam, B ;
Klebert, M ;
Martinez, A ;
Chiesi, A ;
Tomino, C ;
Deeks, S ;
Testa, M ;
Nevin, T ;
Levin, J ;
French, V ;
Fennell, O ;
Stevens, M ;
Grosso, R ;
Dusak, B ;
Hodder, S ;
Squibb, M ;
Brothers, C ;
Tolson, J ;
Leavitt, R ;
Manion, D ;
Ruiz, N ;
Morrisey, K ;
Quart, B ;
Jennings, C ;
Dascomb, S ;
Cooper, M ;
Murphy, M ;
Blakelock, K ;
Doolan, A .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (24) :2293-2303
[27]   The NEAT study: A 48-week open-label study to compare the antiviral efficacy and safety of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1-infected patients [J].
Rodriguez-French, A ;
Boghossian, J ;
Gray, GE ;
Nadler, JP ;
Quinones, AR ;
Sepulveda, GE ;
Millard, JM ;
Wannamaker, PG .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2004, 35 (01) :22-32
[28]   Impact of HIV-1 genetic diversity on plasma HIV-1 RNA quantification -: Usefulness of the Agence Nationale de Recherches sur le SIDA second-generation long terminal repeat-based real-time reverse transcriptase polymerase chain reaction test [J].
Rouet, Francois ;
Chaix, Marie-Laure ;
Nerrienet, Eric ;
Ngo-Giang-Huong, Nicole ;
Plantier, Dean-Christophe ;
Burgard, Marianne ;
Peeters, Martine ;
Damond, Florence ;
Ekouevi, Didier Koumavi ;
Msellati, Philippe ;
Ferradini, Laurent ;
Rukobo, Sandra ;
Marechal, Valerie ;
Schvachsa, Nilda ;
Wakrim, Lahcen ;
Rafalimanana, Christian ;
Rakotoambinina, Benjamin ;
Viard, Jean-Paul ;
Seigneurin, Jean-Marie ;
Rouzioux, Christine .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2007, 45 (04) :380-388
[29]   Early levels of HIV-1 DNA in peripheral blood mononuclear cells are predictive of disease progression independently of HIV-1 RNA levels and CD4+ T cell counts [J].
Rouzioux, C ;
Hubert, JB ;
Burgard, M ;
Deveau, C ;
Goujard, C ;
Bary, M ;
Séréni, D ;
Viard, JP ;
Delfraissy, JF ;
Meyer, L .
JOURNAL OF INFECTIOUS DISEASES, 2005, 192 (01) :46-55
[30]   HIV-1 proviral DNA excision using an evolved recombinase [J].
Sarkar, Indrani ;
Hauber, Ilona ;
Hauber, Joachim ;
Buchholz, Frank .
SCIENCE, 2007, 316 (5833) :1912-1915