Journal ArticleDOI
Quantitative detection of HIV-1 drug resistance mutations by automated DNA sequencing.
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TLDR
A comparison has been made between manual and automated DNA sequencing procedures to evaluate the ability to distinguish mixtures of wild-type and mutant sequences, and software that automatically reports mixed-base positions is presented.Abstract:
A comparison has been made between manual and automated DNA sequencing procedures to evaluate the ability to distinguish mixtures of wild-type and mutant sequences. Quantitative detection of such mixtures of HIV-1 drug resistance mutations was best achieved using an automated system that uses fluorescent-labelled sequencing primers. This procedure has a wide range of applications in clinical research, including heterozygote analysis. Software that automatically reports mixed-base positions is presented.read more
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Journal ArticleDOI
Viral dynamics in human immunodeficiency virus type 1 infection
Xiping Wei,Sajal Ghosh,Maria E. Taylor,Victoria A. Johnson,Emilio A. Emini,Deutsch Paul J,Jeffrey D. Lifson,Sebastian Bonhoeffer,Martin A. Nowak,Beatrice H. Hahn,Michael S. Saag,George M. Shaw +11 more
TL;DR: Almost complete replacement of wild-type virus in plasma by drug-resistant variants occurs after fourteen days, indicating that HIV-1 viraemia is sustained primarily by a dynamic process involving continuous rounds of de novo virus infection and replication and rapid cell turnover.
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Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy
TL;DR: In vivo AZT-3TC combination therapy resulted in a markedly greater decreased in serum HIV-1 RNA concentrations than treatment with AZT alone, even though valine-184 mutants rapidly emerged, consistent with in vitro mutation studies.
Journal ArticleDOI
A Rapid Method for Simultaneous Detection of Phenotypic Resistance to Inhibitors of Protease and Reverse Transcriptase in Recombinant Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Antiretroviral Drugs
Kurt Hertogs,Marie-Pierre de Béthune,Veronica Miller,Tania Ivens,Patricia Schel,Anja Van Cauwenberge,Christel Van den Eynde,Veerle van Gerwen,Hilde Azijn,Margriet Van Houtte,Frank Peeters,Schlomo Staszewski,Marcus A. Conant,Stuart Bloor,S. D. Kemp,Brendan Larder,Rudi Pauwels +16 more
TL;DR: A new method for high-throughput analysis of clinical samples that permits the simultaneous detection of HIV type 1 (HIV-1) phenotypic resistance to both RT and PR inhibitors by means of recombinant virus assay technology is described.
Journal ArticleDOI
TMC114, a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor Active against Protease Inhibitor-Resistant Viruses, Including a Broad Range of Clinical Isolates
Sandra De Meyer,Hilde Azijn,Dominique Louis Nestor Ghislain Surleraux,Dirk Jochmans,Abdellah Tahri,Rudi Pauwels,Piet Wigerinck,Marie-Pierre de Béthune +7 more
TL;DR: TMC114 is a potential candidate for the treatment of both naïve and PI-experienced patients with HIV and Combinations with ritonavir, nelfinavir, and amprenavir showed some evidence of synergy.
Journal ArticleDOI
TMC125, a Novel Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor Active against Nonnucleoside Reverse Transcriptase Inhibitor-Resistant Human Immunodeficiency Virus Type 1
Koen Andries,Hilde Azijn,Theo Thielemans,Donald Ludovici,Michael Joseph Kukla,Jan Heeres,Paul Adriaan Jan Janssen,Corte Bart De,Johan Vingerhoets,Rudi Pauwels,Marie-Pierre de Béthune +10 more
TL;DR: The emerging clinical candidate, TMC125, was highly active against wild-type HIV-1 and showed some activity against HIV-2 and retained activity against 97% of 1,081 recent clinically derived recombinant viruses resistant to at least one of the currently marketed NNRTIs.
References
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Journal ArticleDOI
Fluorescence detection in automated DNA sequence analysis
Lloyd M. Smith,Jane Z. Sanders,Robert J. Kaiser,Peter Hughes,Chris Dodd,Charles R. Connell,Cheryl Heiner,Stephen B. H. Kent,Leroy Hood +8 more
TL;DR: A method for the partial automation of DNA sequence analysis by means of a fluorophore covalently attached to the oligonucleotide primer used in enzymaticDNA sequence analysis.
Journal ArticleDOI
Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT).
Brendan Larder,S. D. Kemp +1 more
TL;DR: The reproducible nature of these mutations should make it possible to develop rapid assays to predict zidovudine resistance by performing polymerase chain reaction amplification of nucleic acid from peripheral blood lymphocytes, thereby circumventing current lengthy HIV isolation and sensitivity testing.
Journal ArticleDOI
An improved method for directly sequencing PCR amplified material using dimethyl sulphoxide.
Journal ArticleDOI
Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture.
Douglas D. Richman,Cheng-Kon Shih,Israel Lowy,Janice M. Rose,Patricia C. Prodanovich,Stephen P. Goff,Johanna A. Griffin +6 more
TL;DR: HIV-1 variants resistant to nevirapine emerged with passage in cell culture in the presence of drug and was stable with continued passage in the absence of drug, while mutants were also resistant to a tetrahydroimidazo and retained their sensitivity to the other reverse transcriptase inhibitors.
Journal ArticleDOI
Zidovudine resistance predicted by direct detection of mutations in DNA from HIV-infected lymphocytes.
TL;DR: A series of infectious HIV variants with specific combinations of mutations in the RT gene were constructed and their sensitivity to zidovudine was assessed by direct detection of specific mutations in DNA from peripheral-blood lymphocyte samples to establish the clinical significance of the resistant isolates.
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