Interruption of reverse transcriptase inhibitors or a switch from reverse transcriptase to protease inhibitors resulted in a fast reappearance of virus strains with a reverse transcriptase inhibitor-sensitive genotype.

作者: Chris Verhofstede , Filip Van Wanzeele , Bea Van Der Gucht , Nancy De Cabooter , Jean Plum

DOI: 10.1097/00002030-199912240-00007

关键词: LentivirusReverse-transcriptase inhibitorProteaseReverse transcriptaseGeneGenotypeBiologyMolecular biologyMutantVirusVirology

摘要: Objectives: To study the effect of interruption reverse transriptase inhibitor (RTI) therapy or a switch from RTI to protease inhibitors, on genotypic drug-resistance pattern plasma HIV-1. Methods: Nine patients who completely stopped all medication, and five switched treatment with regimen containing inhibitors only, were studied. Direct sequencing HIV-1 RT gene was performed follow-up samples taken before after treatment. Results: Comparison amino acid sequence genes in successive showed rapid reappearance wild-type viral variants 12 14 Wild-type virus replaced mutant strains days 2 months therapy, even long history. Conclusion: The results this indicate sustained lower fitness vivo. As result, remains capable outcompeting very fast removal drug. These findings highlight importance 'treatment history' addition phenotypic markers determined at one time-point, when making therapeutic decisions for patients.

参考文章(15)
Staszewski S, Hill Am, Berger A, Sabin C, Phillips An, Miller, Rebound of HIV-1 viral load after suppression to very low levels. AIDS. ,vol. 12, pp. 2360- ,(1998)
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
J Albert, J Wahlberg, J Lundeberg, S Cox, E Sandström, B Wahren, M Uhlén, Persistence of azidothymidine-resistant human immunodeficiency virus type 1 RNA genotypes in posttreatment sera. Journal of Virology. ,vol. 66, pp. 5627- 5630 ,(1992) , 10.1128/JVI.66.9.5627-5630.1992
S. Land, C. McGavin, R. Lucas, C. Birch, Incidence of zidovudine-resistant human immunodeficiency virus isolated from patients before, during, and after therapy. The Journal of Infectious Diseases. ,vol. 166, pp. 1139- 1142 ,(1992) , 10.1093/INFDIS/166.5.1139
L M Frenkel, L E Wagner, S M Atwood, T J Cummins, S Dewhurst, Specific, sensitive, and rapid assay for human immunodeficiency virus type 1 pol mutations associated with resistance to zidovudine and didanosine. Journal of Clinical Microbiology. ,vol. 33, pp. 342- 347 ,(1995) , 10.1128/JCM.33.2.342-347.1995
Menno D. de Jong, Rob J. de Boer, Frank de Wolf, Norbert A. Foudraine, Charles A.B. Boucher, Jaap Goudsmit, Joep M.A. Lange, Overshoot of HIV-1 viraemia after early discontinuation of antiretroviral treatment AIDS. ,vol. 11, ,(1997) , 10.1097/00002030-199711000-00002
Martin S. Hirsch, Brian Conway, Richard T. D'Aquila, Victoria A. Johnson, Françoise Brun-Vézinet, Bonaventura Clotet, Lisa M. Demeter, Scott M. Hammer, Donna M. Jacobsen, Daniel R. Kuritzkes, Clive Loveday, John W. Mellors, Stefano Vella, Douglas D. Richman, for the International AIDS Society–USA Panel, Antiretroviral drug resistance testing in adults with HIV infection: Implications for clinical management JAMA. ,vol. 279, pp. 1984- 1991 ,(1998) , 10.1001/JAMA.279.24.1984