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Titolo:
A rapid non-culture-based assay for clinical monitoring of phenotypic resistance of human immunodeficiency virus type 1 to lamivudine (3TC)
Autore:
Lerma, JGG; Schinazi, RF; Juodawlkis, AS; Soriano, V; Lin, YL; Tatti, K; Rimland, D; Folks, TM; Heneine, W;
Indirizzi:
CtrGAis Control & Prevent, HIV & Retrovirol Branch, Div AIDS STD, Atlanta,Ctr Dis Control & Prevent Atlanta GA USA 30333 ch, Div AIDS STD, Atlanta, Ctr Dis Control & Prevent, TB Lab Res, Atlanta, GA 30333 USA Ctr Dis Control & Prevent Atlanta GA USA 30333 Res, Atlanta, GA 30333 USA Emory Univ, Dept Pediat, Decatur, GA USA Emory Univ Decatur GA USAEmory Univ, Dept Pediat, Decatur, GA USA Emory Univ, Dept Med, Decatur, GA USA Emory Univ Decatur GA USAEmory Univ, Dept Med, Decatur, GA USA Emory Univ, Georgia Vet Affairs Res Ctr AIDS & HIV Infect, Decatur, GA USAEmory Univ Decatur GA USA irs Res Ctr AIDS & HIV Infect, Decatur, GA USA Instid,lud Carlos III, Hosp Carlos III, Serv Enfermedades Infecciosas, Madr Inst Salud Carlos III Madrid Spain Serv Enfermedades Infecciosas, Madr
Titolo Testata:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 2, volume: 43, anno: 1999,
pagine: 264 - 270
SICI:
0066-4804(199902)43:2<264:ARNAFC>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIV-1 REVERSE-TRANSCRIPTASE; HIGH-LEVEL RESISTANCE; ANTIRETROVIRAL THERAPY; DRUG SUSCEPTIBILITY; COMBINATION THERAPY; ZIDOVUDINE AZT; TRANSMISSION; INFECTION; MUTATIONS; VARIANTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Heneine, W Ctrtons Control & Prevent, HIV & Retrovirol Branch, Div AIDS STD, 1600 Clif Ctr Dis Control & Prevent 1600 Clifton Rd NE,MS G-19 Atlanta GA USA 30333
Citazione:
J.G.G. Lerma et al., "A rapid non-culture-based assay for clinical monitoring of phenotypic resistance of human immunodeficiency virus type 1 to lamivudine (3TC)", ANTIM AG CH, 43(2), 1999, pp. 264-270

Abstract

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-resistantHIV-1. We developed a novel non-culture-based assay for the rapid analysisof phenotypic resistance to 3TC of HIV-1 in plasma. The assay measures thesusceptibility 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 5mu M 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 bythe;Imp-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 185 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.

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Documento generato il 04/04/20 alle ore 08:42:57