Abstract
Upon prolonged treatment with various antiretroviral nucleoside analogs such as 3'-azido-3'-deoxythymidine, 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, (-)- beta-L-2', 3'dideoxy-3'thiacytidine and 2',3'-didehydro-3'-deoxythymidine, selection of human immunodeficiency virus type 1 (HIV-1) strains with mutations in the reverse transcriptase (RT) gene has been reported. We designed a reverse hybridization line probe assay (LiPA) for the rapid and simultaneous characterization of the following variations in the RT gene: M41 or L41; T69, N69, A69, or D69; K70 or R70; L74 or V74; V75 or T75; M184, I184, or V184; T215, Y215, or F215; and K219, Q219, or E219. Nucleotide polymorphisms for codon L41 (TTG or CTG), T69 (ACT or ACA), V75 (GTA or GTG), T215 (ACC or ACT), and Y215 (TAC or TAT) could be detected. In addition to the codons mentioned above, several third-letter polymorphisms in the direct vicinity of the target codons (E40, E42, K43, K73, D76, Q182, Y183, D185, G213, F214, and L214) were found, and specific probes were selected. In total, 48 probes were designed and applied to the LiPA test strips and optimized with a well-characterized and representative reference panel. Plasma samples from 358 HIV-infected patients were analyzed with all 48 probes. The amino acid profiles could be deduced by LiPA hybridization in an average of 92.7% of the samples for each individual codon. When combined with changes in viral load and CD4+ T-cell count, this LiPA approach proved to be useful in studying genetic resistance in follow-up samples from antiretroviral agent-treated HIV-1-infected individuals.
Full Text
The Full Text of this article is available as a PDF (1.4 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boucher C. A., Cammack N., Schipper P., Schuurman R., Rouse P., Wainberg M. A., Cameron J. M. High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother. 1993 Oct;37(10):2231–2234. doi: 10.1128/aac.37.10.2231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Clercq E. Antiviral therapy for human immunodeficiency virus infections. Clin Microbiol Rev. 1995 Apr;8(2):200–239. doi: 10.1128/cmr.8.2.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eastman P. S., Boyer E., Mole L., Kolberg J., Urdea M., Holodniy M. Nonisotopic hybridization assay for determination of relative amounts of genotypic human immunodeficiency virus type 1 zidovudine resistance. J Clin Microbiol. 1995 Oct;33(10):2777–2780. doi: 10.1128/jcm.33.10.2777-2780.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frenkel L. M., Wagner L. E., 2nd, Atwood S. M., Cummins T. J., Dewhurst S. Specific, sensitive, and rapid assay for human immunodeficiency virus type 1 pol mutations associated with resistance to zidovudine and didanosine. J Clin Microbiol. 1995 Feb;33(2):342–347. doi: 10.1128/jcm.33.2.342-347.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Furman P. A., Fyfe J. A., St Clair M. H., Weinhold K., Rideout J. L., Freeman G. A., Lehrman S. N., Bolognesi D. P., Broder S., Mitsuya H. Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8333–8337. doi: 10.1073/pnas.83.21.8333. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iversen A. K., Shafer R. W., Wehrly K., Winters M. A., Mullins J. I., Chesebro B., Merigan T. C. Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. J Virol. 1996 Feb;70(2):1086–1090. doi: 10.1128/jvi.70.2.1086-1090.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Japour A. J., Mayers D. L., Johnson V. A., Kuritzkes D. R., Beckett L. A., Arduino J. M., Lane J., Black R. J., Reichelderfer P. S., D'Aquila R. T. Standardized peripheral blood mononuclear cell culture assay for determination of drug susceptibilities of clinical human immunodeficiency virus type 1 isolates. The RV-43 Study Group, the AIDS Clinical Trials Group Virology Committee Resistance Working Group. Antimicrob Agents Chemother. 1993 May;37(5):1095–1101. doi: 10.1128/aac.37.5.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaye S., Loveday C., Tedder R. S. A microtitre format point mutation assay: application to the detection of drug resistance in human immunodeficiency virus type-1 infected patients treated with zidovudine. J Med Virol. 1992 Aug;37(4):241–246. doi: 10.1002/jmv.1890370402. [DOI] [PubMed] [Google Scholar]
- Larder B. A., Kellam P., Kemp S. D. Zidovudine resistance predicted by direct detection of mutations in DNA from HIV-infected lymphocytes. AIDS. 1991 Feb;5(2):137–144. doi: 10.1097/00002030-199102000-00002. [DOI] [PubMed] [Google Scholar]
- Larder B. A., Kemp S. D., Harrigan P. R. Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science. 1995 Aug 4;269(5224):696–699. doi: 10.1126/science.7542804. [DOI] [PubMed] [Google Scholar]
- Levy J. A., Ramachandran B., Barker E., Guthrie J., Elbeik T. Plasma viral load, CD4+ cell counts, and HIV-1 production by cells. Science. 1996 Feb 2;271(5249):670–671. doi: 10.1126/science.271.5249.670. [DOI] [PubMed] [Google Scholar]
- López-Galíndez C., Rojas J. M., Nájera R., Richman D. D., Perucho M. Characterization of genetic variation and 3'-azido-3'-deoxythymidine- resistance mutations of human immunodeficiency virus by the RNase A mismatch cleavage method. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4280–4284. doi: 10.1073/pnas.88.10.4280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mellors J. W., Rinaldo C. R., Jr, Gupta P., White R. M., Todd J. A., Kingsley L. A. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. 1996 May 24;272(5265):1167–1170. doi: 10.1126/science.272.5265.1167. [DOI] [PubMed] [Google Scholar]
- Richman D. D., Grimes J. M., Lagakos S. W. Effect of stage of disease and drug dose on zidovudine susceptibilities of isolates of human immunodeficiency virus. J Acquir Immune Defic Syndr. 1990;3(8):743–746. [PubMed] [Google Scholar]
- Richman D. D., Guatelli J. C., Grimes J., Tsiatis A., Gingeras T. Detection of mutations associated with zidovudine resistance in human immunodeficiency virus by use of the polymerase chain reaction. J Infect Dis. 1991 Dec;164(6):1075–1081. doi: 10.1093/infdis/164.6.1075. [DOI] [PubMed] [Google Scholar]
- Richman D. D. HIV drug resistance. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1065–1071. doi: 10.1089/aid.1992.8.1065. [DOI] [PubMed] [Google Scholar]
- Richman D. D. Resistance of clinical isolates of human immunodeficiency virus to antiretroviral agents. Antimicrob Agents Chemother. 1993 Jun;37(6):1207–1213. doi: 10.1128/aac.37.6.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schinazi R. F., Lloyd R. M., Jr, Nguyen M. H., Cannon D. L., McMillan A., Ilksoy N., Chu C. K., Liotta D. C., Bazmi H. Z., Mellors J. W. Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. Antimicrob Agents Chemother. 1993 Apr;37(4):875–881. doi: 10.1128/aac.37.4.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schinazi R. F., Mead J. R., Feorino P. M. Insights into HIV chemotherapy. AIDS Res Hum Retroviruses. 1992 Jun;8(6):963–990. doi: 10.1089/aid.1992.8.963. [DOI] [PubMed] [Google Scholar]
- Stuyver L., Rossau R., Wyseur A., Duhamel M., Vanderborght B., Van Heuverswyn H., Maertens G. Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J Gen Virol. 1993 Jun;74(Pt 6):1093–1102. doi: 10.1099/0022-1317-74-6-1093. [DOI] [PubMed] [Google Scholar]
- Stuyver L., Wyseur A., van Arnhem W., Hernandez F., Maertens G. Second-generation line probe assay for hepatitis C virus genotyping. J Clin Microbiol. 1996 Sep;34(9):2259–2266. doi: 10.1128/jcm.34.9.2259-2266.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]