Journal ArticleDOI
A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors.
Bluma G. Brenner,Dan Turner,Maureen Oliveira,Daniela Moisi,Mervi Detorio,Mauricio Carobene,Richard Marlink,Jonathan M. Schapiro,Michel Roger,Mark A. Wainberg +9 more
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TLDR
V106M may be a signature mutation in clade C patients treated with EFV and may have the potential to confer high-level multi-NNRTI resistance.Abstract:
OBJECTIVE: We have shown that HIV-1 clade C variants contain a valine codon 106 polymorphism (GTG) that facilitates a V106M transition (GTG<--ATG) after selection with efavirenz (EFV). This study evaluates the prevalence of V106 (GTG) and 106M (ATG) codons in clinical isolates as well as the effects of V106M on resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). METHODS: Genotypic analysis ascertained sequence diversity at codon 106, including both valine polymorphisms (GTA and GTG) and the V106A (GCA) and V106M (ATG) resistance-conferring mutations in B (n = 440) and non-B (n = 84) clinical isolates. Cell-based phenotypic assays were performed to determine the effects of V106M and V106A on levels of resistance to EFV, nevirapine and delavirdine. RESULTS: Most subtype B isolates harbored GTA (valine) at codon 106 (97% of cases) while the GTG (valine) polymorphism was generally present in clade C viruses (94% of cases). Under conditions of EFV but not nevirapine or delavirdine pressure (n = 8) in tissue culture, clade C isolates developed the V106M mutation (GTG<--ATG), conferring high-level (100-1000-fold) cross-resistance to all NNRTI. Generation of V106M recombinant viruses by site-directed mutagenesis confirmed the ability of V106M to confer NNRTI cross-resistance. This mutation also developed in three of six EFV-treated patients harboring clade C infections. In current genotypic interpretative reports (including 15 algorithmic databases), V106A is listed as an nevirapine-specific mutation while V106M is not recognized. CONCLUSIONS: V106M may be a signature mutation in clade C patients treated with EFV and may have the potential to confer high-level multi-NNRTI resistance.read more
Citations
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Journal ArticleDOI
British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008
Brian Gazzard,Jane Anderson,Abdel Babiker,Marta Boffito,Gary Brook,Gary Brough,Duncan Churchill,Ben Cromarty,Satyajit Das,Martin Fisher,Andrew L. Freedman,Anna Maria Geretti,Margaret A. Johnson,Saye Khoo,Clifford Leen,Devaki Nair,Barry Peters,Andrew N. Phillips,Deenan Pillay,Anton Pozniak,John P. Walsh,Ed Wilkins,Ian S. Williams,Matthew Williams,M Youle +24 more
TL;DR: The 2008 BHIVA Guidelines have been updated to incorporate all the new relevant information since the last iteration and all the peer-reviewed publications and important, potentially treatment-changing abstracts from the last 2 years have been reviewed.
Journal ArticleDOI
HIV-1 Antiretroviral Drug Therapy
Eric J. Arts,Daria J. Hazuda +1 more
TL;DR: The basic principles of antiretroviral drug therapy, the mode of drug action, and the factors leading to treatment failure are reviewed (i.e., drug resistance).
Journal ArticleDOI
Web resources for HIV type 1 genotypic-resistance test interpretation.
Tommy F. Liu,Robert W. Shafer +1 more
TL;DR: In this article, the authors describe the scientific principles of HIV-1 genotypic-drug-resistance test interpretation and the most commonly used Web-based resources for clinicians ordering GENotypic drug-resistant tests.
Journal ArticleDOI
Antiretroviral Drug Resistance Testing in Adult HIV-1 Infection: 2008 Recommendations of an International AIDS Society-USA Panel
Martin S. Hirsch,Huldrych F. Günthard,Jonathan M. Schapiro,Françoise Brun-Vézinet,Bonaventura Clotet,Scott M. Hammer,Victoria A. Johnson,Victoria A. Johnson,Daniel R. Kuritzkes,John W. Mellors,Deenan Pillay,Patrick Yeni,Donna M. Jacobsen,Douglas D. Richman,Douglas D. Richman +14 more
TL;DR: A panel of physicians and scientists with expertise in drug-resistant HIV-1, drug management, and patient care is convened to review recently published data and presentations at scientific conferences and to provide updated recommendations on resistance testing.
Journal ArticleDOI
Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an International AIDS Society-USA Panel.
Martin S. Hirsch,Françoise Brun-Vézinet,Bonaventura Clotet,Brian Conway,Daniel R. Kuritzkes,Richard T. D'Aquila,Lisa M. Demeter,Scott M. Hammer,Victoria A. Johnson,Clive Loveday,John W. Mellors,Donna M. Jacobsen,Douglas D. Richman +12 more
TL;DR: The International AIDS Society-USA convened a panel of physicians and scientists with expertise in antiretroviral drug management, HIV-1 drug resistance, and patient care to provide updated recommendations for HIV- 1 resistance testing.
References
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Journal ArticleDOI
Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.
Frank J. Palella,Kathleen M. Delaney,Anne C. Moorman,Mark O. Loveless,Jack Fuhrer,Glen A. Satten,Diane J. Aschman,Scott D. Holmberg +7 more
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Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection
TL;DR: A study was conducted to evaluate the impact of protease inhibitors on the rates of selected opportunistic processes and mortality in patients with AIDS and found similar results.
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Efavirenz plus Zidovudine and Lamivudine, Efavirenz plus Indinavir, and Indinavir plus Zidovudine and Lamivudine in the Treatment of HIV-1 Infection in Adults
Schlomo Staszewski,Javier O Morales-Ramirez,Karen T. Tashima,Anita Rachlis,Daniel J. Skiest,James F. Stanford,Richard Stryker,Philip J. Johnson,Dominic F. Labriola,Dianne Farina,Douglas J. Manion,Nancy M. Ruiz +11 more
TL;DR: As antiretroviral therapy in HIV-1-infected adults, the combination of efavirenz, zidovudine, and lamivudine has greater antiviral activity and is better tolerated than the combination.
Mutations in Retroviral Genes Associated with Drug Resistance
TL;DR: The growing number of drug resistance mutations listed in this revised table stands as a testimony to the genetic flexibility of HIV.
Drug Resistance Mutations in HIV-1.
Victoria A. Johnson,F. Brun-Vezinet,Bonaventura Clotet,Brian Conway,Richard T. D'Aquila,Lisa M. Demeter,Daniel R. Kuritzkes,Deenan Pillay,Jonathan M. Schapiro,Amalio Telenti,Douglas D. Richman +10 more
TL;DR: Recognizing that virologic failure of the first regimen typically involves HIV-1 isolates with resistance to only 1 or 2 of the drugs in the regimen; in this setting, resistance most commonly develops to lamivudine or the nonnucleoside reverse transcriptase inhibitors.
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