Transient relapses ("blips") of plasma HIV RNA levels during HAART are associated with drug resistance.

作者: James W. T. Cohen Stuart , Annemarie M. J. Wensing , Colin Kovacs , Maike Righart , Dorien de Jong

DOI: 10.1097/00042560-200110010-00001

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摘要: Introduction: In a large number of patients on HAART who achieved plasma HIV RNA levels below the limit detection (50 copies/ml), transient relapses (blips) are observed. Objective: To determine whether during associated with development drug resistance. Methods: Plasma samples from 15 viral load relapse were studied. All regimens contained lamivudine (3TC). We used an ultra-sensitive sequence approach to analyze presence resistance mutations relapse. Results: The median was 76 copies/ml (range 50-1239). 11 cases, genotype could he obtained. Mutations in RT and protease gene conferring one or more drugs observed 8 I patients, 6 whom had M1 84V substitution. During follow-up 27 months after relapse, remained undetectable 13 patients. Conclusions: blips can be selection drug-resistant HIV. This indicates that replication may occur HAART, probably caused by temporary decrease active concentrations A blip containing only wild-type virus is not necessarily replication. this situation raise also originate release viruses, activation latent reservoir. Independent mechanism, did preclude successful inhibition 2-year majority these cases.

参考文章(33)
R. Schuurman, C. A. B. Boucher, M. Nijhuis, Sensitive procedure for the amplification of HIV-1 RNA using a combined reverse-transcription and amplification reaction. BioTechniques. ,vol. 19, pp. 178- 182 ,(1995)
D D Ho, T Toyoshima, H Mo, D J Kempf, D Norbeck, C M Chen, N E Wideburg, S K Burt, J W Erickson, M K Singh, Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor. Journal of Virology. ,vol. 68, pp. 2016- 2020 ,(1994) , 10.1128/JVI.68.3.2016-2020.1994
N. K. Back, M. Nijhuis, W. Keulen, C. A. Boucher, B. O. Oude Essink, A. B. van Kuilenburg, A. H. van Gennip, B. Berkhout, Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. The EMBO Journal. ,vol. 15, pp. 4040- 4049 ,(1996) , 10.1002/J.1460-2075.1996.TB00777.X
N. E. Kohl, E. A. Emini, W. A. Schleif, L. J. Davis, J. C. Heimbach, R. A. Dixon, E. M. Scolnick, I. S. Sigal, Active human immunodeficiency virus protease is required for viral infectivity. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 85, pp. 4686- 4690 ,(1988) , 10.1073/PNAS.85.13.4686
B. Autran, G. Carcelain, T. S. Li, C. Blanc, D. Mathez, R. Tubiana, C. Katlama, P. Debré, J. Leibowitch, Positive Effects of Combined Antiretroviral Therapy on CD4+ T Cell Homeostasis and Function in Advanced HIV Disease Science. ,vol. 277, pp. 112- 116 ,(1997) , 10.1126/SCIENCE.277.5322.112
S I Staprans, B L Hamilton, S E Follansbee, T Elbeik, P Barbosa, R M Grant, M B Feinberg, ACTIVATION OF VIRUS REPLICATION AFTER VACCINATION OF HIV-1-INFECTED INDIVIDUALS Journal of Experimental Medicine. ,vol. 182, pp. 1727- 1737 ,(1995) , 10.1084/JEM.182.6.1727
Joseph A. Kovacs, Michael Baseler, Robin J. Dewar, Susan Vogel, Richard T. Davey, Judith Falloon, Michael A. Polis, Robert E. Walker, Randy Stevens, Norman P. Salzman, Julia A. Metcalf, Henry Masur, H. Clifford Lane, Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. The New England Journal of Medicine. ,vol. 332, pp. 567- 575 ,(1995) , 10.1056/NEJM199503023320904
Daniel R. Kuritzkes, Joseph B. Quinn, Sharon L. Benoit, David L. Shugarts, Aaron Griffin, Minoo Bakhtiari, David Poticha, Joseph J. Eron, Mary Ann Fallon, Marc Rubin, Drug resistance and virologic response in NUCA 3001, a randomized trial of lamivudine (3TC) versus zidovudine (ZDV) versus ZDV plus 3TC in previously untreated patients. AIDS. ,vol. 10, pp. 975- 981 ,(1996) , 10.1097/00002030-199610090-00007
Joseph J. Eron, Sharon L. Benoit, Joseph Jemsek, Rodger D. MacArthur, Jorge Santana, Joseph B. Quinn, Daniel R. Kuritzkes, Mary Ann Fallon, Marc Rubin, Treatment with Lamivudine, Zidovudine, or Both in HIV-Positive Patients with 200 to 500 CD4+ Cells per Cubic Millimeter The New England Journal of Medicine. ,vol. 333, pp. 1662- 1669 ,(1995) , 10.1056/NEJM199512213332502
Franco Tozzini, Donatella Matteucci, Patrizia Bandecchi, Fulvia Baldinotti, Alessandro Poli, Mauro Pistello, Kees H.J. Siebelink, Luca Ceccherini-Nelli, Mauro Bendinelli, Simple in vitro methods for titrating feline immunodeficiency virus (FIV) and FIV neutralizing antibodies. Journal of Virological Methods. ,vol. 37, pp. 241- 252 ,(1992) , 10.1016/0166-0934(92)90026-A