{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:22:54Z","timestamp":1788225774683,"version":"build-2803163510"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1999,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Monitoring for lamivudine (3TC) resistance is important both for the clinical management of human immunodeficiency virus type 1 (HIV-1)-infected patients treated with 3TC and for surveillance of transmission of 3TC-resistant HIV-1. We developed a novel non-culture-based assay for the rapid analysis of phenotypic resistance to 3TC of HIV-1 in plasma. The assay measures the susceptibility of HIV-1 reverse transcriptase (RT) activity to 3TC triphosphate (3TC-TP) in plasma. RT detection was done by the Amp-RT assay, an ultrasensitive PCR-based RT assay. Under our assay conditions, we found that 5 \u03bcM 3TC-TP inhibited RT activity from wild-type (WT), zidovudine-resistant, or nevirapine-resistant HIV-1 but not from HIV-1 carrying either the M184V mutation or multidrug (MD) resistance mutations (77L\/116Y\/151M or 62V\/75I\/77L\/116Y\/151M). Mixing experiments showed a detection threshold of 10% 3TC-resistant virus (M184V) in a background of WT HIV-1. To validate the assay for the detection of phenotypic resistance of HIV-1 to 3TC in plasma samples, HIV-1 RT in 30 plasma specimens collected from 15 patients before and during therapy with 3TC was tested for evidence of phenotypic resistance by the Amp-RT assay. The results were compared with those of genotypic analysis. The RT in 12 samples was found to be 3TC sensitive, while the RT in 18 samples had evidence of phenotypic resistance. All 12 samples with 3TC-sensitive RT had WT genotypes at codon 184 and were retrieved before treatment with 3TC. In contrast, all 18 specimens with 3TC-resistant RT were posttherapy samples. This assay provides a simple, rapid, and reliable method for the detection of phenotypic resistance of HIV-1 to 3TC in plasma.<\/jats:p>","DOI":"10.1128\/aac.43.2.264","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:34:13Z","timestamp":1539045253000},"page":"264-270","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["A Rapid Non-Culture-Based Assay for Clinical Monitoring of Phenotypic Resistance of Human Immunodeficiency Virus Type 1 to Lamivudine (3TC)"],"prefix":"10.1128","volume":"43","author":[{"given":"J. Gerardo","family":"Garci\u0301a Lerma","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Atlanta, Georgia1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F.","family":"Schinazi","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Georgia Veterans Affairs Research Center for AIDS and HIV Infections, and Department of Pediatrics and Department of Medicine, Emory University, Decatur, Georgia2; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Juodawlkis","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Georgia Veterans Affairs Research Center for AIDS and HIV Infections, and Department of Pediatrics and Department of Medicine, Emory University, Decatur, Georgia2; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Soriano","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Servicio de Enfermedades Infecciosas, Hospital Carlos III, Instituto de Salud Carlos III, Madrid, Spain3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Lin","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Georgia Veterans Affairs Research Center for AIDS and HIV Infections, and Department of Pediatrics and Department of Medicine, Emory University, Decatur, Georgia2; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Tatti","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Georgia Veterans Affairs Research Center for AIDS and HIV Infections, and Department of Pediatrics and Department of Medicine, Emory University, Decatur, Georgia2; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rimland","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Georgia Veterans Affairs Research Center for AIDS and HIV Infections, and Department of Pediatrics and Department of Medicine, Emory University, Decatur, Georgia2; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Folks","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Atlanta, Georgia1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Heneine","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Atlanta, Georgia1;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.3.527"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.2.712-720.1996"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.10.2231"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2165\/00003495-199753040-00008","article-title":"Lamivudine: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection.","volume":"53","author":"Caroline M. P.","year":"1997","unstructured":"Caroline M. P. Faulds D. Lamivudine: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs 53 1997 657 680","journal-title":"Drugs"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1001\/jama.1997.03540480062040","article-title":"Antiviral therapy for HIV infection in 1997: updated recommendations of the International AIDS Society\u2014USA panel.","volume":"277","author":"Carpenter C. C.","year":"1997","unstructured":"Carpenter C. C. Fischl M. A. Hammer S. M. Hirsch M. S. Jacobsen D. M. Katzenstein D. A. Montaner J. S. Richman D. D. Saag M. S. Schooley R. T. Thompson M. A. Vella S. Yeni P. G. Volberding P. A. Antiviral therapy for HIV infection in 1997: updated recommendations of the International AIDS Society\u2014USA panel. JAMA 277 1997 1962 1969","journal-title":"JAMA"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(84)90007-4"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/infdis\/169.2.411","article-title":"Heterosexual transmission of human immunodeficiency virus type 1 variants associated with zidovudine resistance.","volume":"169","author":"Conlon C. P.","year":"1994","unstructured":"Conlon C. P. Klenerman P. Edwards A. Larder B. A. Phillips R. E. Heterosexual transmission of human immunodeficiency virus type 1 variants associated with zidovudine resistance. J. Infect. Dis. 169 1994 411 415","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_9_2","unstructured":"D\u2019Aquila\n              R. T.\n          Nucleosides and foscarnet: clinical aspects\n          Antiviral drug resistance.\n              Richman\n              D. D.\n          1996\n          191\n          224\n          John Wiley & Sons Inc.\n          New York N.Y"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1056\/NEJM199304223281605","article-title":"Brief report: primary infection with zidovudine-resistant human immunodeficiency virus type 1.","volume":"328","author":"Erice A.","year":"1993","unstructured":"Erice A. Mayers D. L. Strike D. G. Sannerud K. J. McCutchan F. E. Henry K. Balfour H. H. Brief report: primary infection with zidovudine-resistant human immunodeficiency virus type 1. N. Engl. J. Med. 328 1993 1163 1165","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.10.1729"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.1.153"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1086\/515272","article-title":"Measurement of human immunodeficiency virus type 1 plasma virus load based on reverse transcriptase (RT) activity: evidence of variabilities in levels of virion-associated RT.","volume":"177","author":"Garcia Lerma J. G.","year":"1998","unstructured":"Garcia Lerma J. G. Yamamoto S. Gomez-Cano M. Soriano V. Green T. A. Busch M. P. Folks T. M. Heneine W. Measurement of human immunodeficiency virus type 1 plasma virus load based on reverse transcriptase (RT) activity: evidence of variabilities in levels of virion-associated RT. J. Infect. Dis. 177 1998 1221 1229","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709113371102"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/171.5.1210"},{"key":"e_1_3_2_16_2","unstructured":"Heneine\n              W.\n              Garcia Lerma\n              J. G.\n              Vazquez-Rosales\n              J. G.\n              Qari\n              S.\n              Juodawlkis\n              A.\n              Havlir\n              D.\n              Schinazi\n              R. F.\n              Richman\n              D. D.\n              Folks\n              T. M.\n          A novel non culture-based approach for the rapid analysis of phenotypic resistance to reverse transcriptase inhibitors of HIV-1 from plasma abstr. 63\n          Program and abstracts of the 2nd International Workshop on Drug Resistance and Treatment Strategies\n          1998\n          42"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.2.269"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/516487"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.2.1086-1090.1996"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/infdis\/175.3.561","article-title":"A novel approach to assessing the drug susceptibility and replication of human immunodeficiency virus type 1 isolates.","volume":"175","author":"Jellinger R. M.","year":"1997","unstructured":"Jellinger R. M. Shafer R. W. Merigan T. C. A novel approach to assessing the drug susceptibility and replication of human immunodeficiency virus type 1 isolates. J. Infect. Dis. 175 1997 561 566","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1086\/515324","article-title":"Emergence of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy.","volume":"177","author":"Kavlik M. F.","year":"1998","unstructured":"Kavlik M. F. Wyvill K. Yarchoan R. Mitsuya H. Emergence of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy. J. Infect. Dis. 177 1998 1506 1513","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0166-3542(95)00044-M","article-title":"Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (\u2212)-2\u2032,3\u2032-dideoxy-3\u2032-thiacytidine.","volume":"28","author":"Kavlick M. F.","year":"1995","unstructured":"Kavlick M. F. Shirasaka T. Kojima E. Pluda J. M. Hui F. Yarchoan R. Mitsuya H. Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (\u2212)-2\u2032,3\u2032-dideoxy-3\u2032-thiacytidine. Antivir. Res. 28 1995 133 146","journal-title":"Antivir. Res."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.1.23"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.2.875-885.1992"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2479983"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2467383"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7542804"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.8.3973-3985.1991"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1021\/jo00264a024","article-title":"Rapid and efficient synthesis of nucleoside 5\u2032-O-(1-thiotriphosphates), 5\u2032-triphosphates and 2\u20323\u2032-cyclophosphorothioates using 2-chlore-4H-1,2,3-benzodioxaphosphorin-4-one.","volume":"54","author":"Ludwig J.","year":"1989","unstructured":"Ludwig J. Eckstein F. Rapid and efficient synthesis of nucleoside 5\u2032-O-(1-thiotriphosphates), 5\u2032-triphosphates and 2\u20323\u2032-cyclophosphorothioates using 2-chlore-4H-1,2,3-benzodioxaphosphorin-4-one. J. Org. Chem. 54 1989 631 635","journal-title":"J. Org. Chem."},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1021\/bi00021a036","article-title":"Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase.","volume":"34","author":"Sarafinos S. G.","year":"1995","unstructured":"Sarafinos S. G. Pandey V. N. Kaushik N. Modak M. J. Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. Biochemistry 34 1995 7207 7216","journal-title":"Biochemistry"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.11.2423"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.4.875"},{"key":"e_1_3_2_33_2","first-page":"129","article-title":"Mutations in retroviral genes associated with drug resistance.","volume":"5","author":"Schinazi R. F.","year":"1997","unstructured":"Schinazi R. F. Larder B. A. Mellors J. W. Mutations in retroviral genes associated with drug resistance. Int. Antivir. News 5 1997 129 142","journal-title":"Int. Antivir. News"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/171.6.1411"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/infdis\/172.1.70","article-title":"Drug resistance and heterogeneous long-term virologic responses of human immunodeficiency virus type 1-infected subjects to zidovudine and didanosine combination therapy.","volume":"172","author":"Shafer R. W.","year":"1995","unstructured":"Shafer R. W. Iversen A. K. N. Winters M. A. Aguiniga E. Katzenstein D. A. Merigan T. C. the AIDS Clinical Trials Group 143 Virology Team Drug resistance and heterogeneous long-term virologic responses of human immunodeficiency virus type 1-infected subjects to zidovudine and didanosine combination therapy. J. Infect. Dis. 172 1995 70 78","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.6.2398"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1716788"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.2.284"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.12.5653"},{"key":"e_1_3_2_40_2","first-page":"556","article-title":"Transmission of zidovudine-resistant human immunodeficiency virus type 1 variants following deliberate injection of blood from a patient with AIDS: characteristics and natural history of the virus.","volume":"21","author":"Veenstra J.","year":"1995","unstructured":"Veenstra J. Schuurman R. Cornelissen M. van\u2019t Wout A. B. Boucher C. A. B. Schuitemaker H. Goudsmit J. Coutinho R. A. Transmission of zidovudine-resistant human immunodeficiency virus type 1 variants following deliberate injection of blood from a patient with AIDS: characteristics and natural history of the virus. J. Infect. Dis. 21 1995 556 560","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/00002030-199509040-00006","article-title":"Development of HIV-1 resistance to (\u2212) 2\u2032-deoxy-3\u2032-thiacytidine in patients with AIDS or advanced AIDS-related complex.","volume":"9","author":"Wainberg M. A.","year":"1995","unstructured":"Wainberg M. A. Salomon H. Gu Z. Montaner J. S. G. Cooley T. P. MaCaffrey R. Ruedy J. Hirst H. M. Cammack N. Cameron J. Nicholson W. Development of HIV-1 resistance to (\u2212) 2\u2032-deoxy-3\u2032-thiacytidine in patients with AIDS or advanced AIDS-related complex. AIDS 9 1995 351 357","journal-title":"AIDS"},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/00002030-199612005-00002","article-title":"Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V substitution in 3TC-resistant HIV-1 reverse transcriptase.","volume":"10","author":"Wainberg M. A.","year":"1996","unstructured":"Wainberg M. A. Hsu M. Gu Z. Borkow G. Parniak M. A. Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V substitution in 3TC-resistant HIV-1 reverse transcriptase. AIDS 10 1996 S3 S10","journal-title":"AIDS"},{"key":"e_1_3_2_43_2","unstructured":"Wainberg\n              M. A.\n              Miller\n              M. D.\n              Quan\n              Y.\n              Salomon\n              H.\n              Cherrington\n              J.\n          The M184V substitution in reverse transcriptase moderately increases sensitivity of HIV-1 to PMPA abstr. 680\n          Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections\n          1998\n          207"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(96)02078-2"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.2.264","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.2.264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:08:15Z","timestamp":1645459695000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.43.2.264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,2]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1999,2]]}},"alternative-id":["10.1128\/AAC.43.2.264"],"URL":"https:\/\/doi.org\/10.1128\/aac.43.2.264","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,2]]},"assertion":[{"value":"1998-07-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-10-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}