PMID: 8585767Oct 1, 1995Paper

Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (--)-2',3'-dideoxy-3'-thiacytidine

Antiviral Research
M F KavlickH Mitsuya

Abstract

We attempted to determine whether HIV-1 developed resistance to (--)-2',3'-dideoxy-3'-thiacytidine ((--)-3TC or 3TC, lamivudine) in patients with advanced human immunodeficiency virus type 1 (HIV-1) infection during therapy with 3TC. Genotypic analysis of HIV-1 strains isolated from 6 patients receiving 3TC revealed that as early as 2 months of therapy, HIV-1 developed a Met to Val amino acid substitution at codon 184 (Met184-->Val) in the reverse transcriptase-coding region of the pol gene. A detailed study of a series of HIV-1 strains isolated from a patient demonstrated that Met at codon 184 was first substituted with Ile by 2 weeks of 3TC therapy, followed by the substitution with Val by 8 weeks. All HIV-1 strains with the Met184-->Val substitution were profoundly less susceptible to 3TC (1800- to 5500-fold decreased sensitivity) as compared to pretherapy virus strains. These strains were also moderately less sensitive to 2',3'-dideoxycytidine (4.5- to 9-fold), but more sensitive to 3'-azido-2',3'-dideoxythymidine (2- to 14-fold). A decrease in viremia levels and an increase in CD4 counts were observed early in therapy; however, these changes were only transient. Our data suggest that reversal of such beneficial changes is ...Continue Reading

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Citations

Jun 16, 2004·Antiviral Research·Youhoon Chong, Chung K Chu
Sep 21, 2000·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·B ZöllnerR Laufs
Mar 5, 2009·Antimicrobial Agents and Chemotherapy·Carolina HerreraRobin J Shattock
Oct 25, 2003·Antimicrobial Agents and Chemotherapy·Karidia DialloM A Wainberg
Apr 1, 2011·Future Microbiology·Shiro Ibe, Wataru Sugiura
Aug 27, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Valentina SvicherCarlo Federico Perno
Jan 25, 2012·International Journal of Antimicrobial Agents·Francesco Scaglione, Liberato Berrino
May 11, 2000·Organic Letters·M T Crimmins, W J Zuercher
Jul 12, 2005·Antiviral Chemistry & Chemotherapy·Prem L SharmaRaymond F Schinazi
Jan 6, 1999·Antiviral Chemistry & Chemotherapy·A M VandammeE De Clercq
Nov 26, 2005·Expert Review of Anti-infective Therapy·Albert M L Anderson, John A Bartlett
May 1, 1997·Antimicrobial Agents and Chemotherapy·S M DalugeT A Krenitsky

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