1st National Conference Human Retroviruses and Related Infections Washington, DC - December 12-16, 1993

Natl Conf Hum Retrovir Relat Infect 1993 Dec 12-16;1: (abstract no. 10)

Boucher C¹, Schuurman R¹, Nijhuis M¹, Van Leeuwen R¹, Danner S¹, Kaye S², Mulder J³, Sninsky J³, Kwok S^3
1University of Amsterdam, Amsterdam, the Netherlands; ²Middlesex School of Medicine, London, UK; ³Roche Molecular Systems, Alameda, CA

The kinetics of retroviral infection were studied in a cohort of 3TC treated individuals. Viral load was determined by the HIV P24 antigen assay, quantitative plasma culture assay and two different RT-PCR approaches. Similar trends were observed with both PCR methods; a sharp decline (1-2 logs) within a week after initiation of treatment followed by a rise to a level still below that of the baseline. In vitro selection experiments with 3TC generated amino acid changes at codon 184 of RT (methionine (ATG) to isoleucine (ATA) or valine (GTG, GTA)) resulting in a highly resistant phenotype. The kinetics of the appearance of the mutations encoding these amino acid changes were monitored in serum samples using a semiquantitative point mutation assay.^[1] The appearance of the change at codon 184 in serum preceded the rise in HIV RNA load. The proviral DNA obtained after 6 months of therapy from 26/40 patients harbored more than 50% mutant viruses. Development of the mutation occurred independently of the virus syncytium inducing capacity. These data suggest that inhibition of viral replication by 3TC can decrease viral load within days. In addition, increase in viral load during therapy may serve as an indirect measure of antiviral resistance. Moreover, the turnover from wild type to mutant viruses indicates that the half life of viral particles in vivo can be short and that persistent infection with HIV is an extremely dynamic process.

Ref: ^[1]S Kaye, et al., “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):241-6

Keywords: Acquired Immunodeficiency Syndrome, Antiviral Agents, Codon, HIV, HIV Core Protein p24, HIV Infections, HIV-1 Reverse Transcriptase, Humans, In Vitro, Lamivudine, Mutation, Phenotype, Viral Load, genetics, immunology, organization & administration

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1993-12-12
10

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