BACKGROUND: To investigate genotypic resistance profiles to emtricitabine + tenofovir (FTC + TDF) in-vivo and in-vitro, and compare them with lamivudine + tenofovir (3TC + TDF). METHODS: Three hundred fifty-two HIV-1 B-subtype pol sequences from 42 FTC + TDF-treated patients, 40 3TC + TDF-treated patients, and 270 patients treated with 3TC plus another nucleoside reverse transcriptase inhibitor (but not TDF). All patients never received FTC, 3TC, and TDF in their previous therapeutic regimen. 3TC/FTC ± TDF resistance was investigated using in vitro selection experiments and docking simulations. RESULTS: The M184V mutation is less prevalent in FTC + TDF-treated patients than in 3TC + TDF-treated, and 3TC-treated/TDF-naive patients (14.3% versus 40.0%, P = 0.01 and 55.6%, P < 0.001). Multivariable analysis shows that factors correlated with a lower probability of M184V emergence at failure were the use of FTC compared with 3TC [odds ratio (OR): 0.32 (95% confidence interval (CI): 0.10 to 0.99), P = 0.04], the use of boosted protease inhibitor, and the use of TDF [OR: 0.20 (95% CI: 0.11 to 0.37), P < 0.001, and OR: 0.47 (95%CI: 0.22 to 1.01), P = 0.05, respectively]. In vitro selection experiments and docking analysis show that other reverse transcriptase (RT) mutations, even localized in RT connection domain, can be selected by 3TC + TDF or FTC + TDF in M184V absence and can affect RT affinity for 3TC/FTC and/or TDF. CONCLUSIONS: Our study shows lower rates of M184V development in FTC + TDF regimens versus 3TC + TDF and suggests a potential role of boosted protease inhibitors and TDF in delaying the M184V emergence. Novel RT mutational patterns, more complex than currently known, can contribute to 3TC, FTC, and TDF resistance.
BACKGROUND: To investigate genotypic resistance profiles to emtricitabine + tenofovir (FTC + TDF) in-vivo and in-vitro, and compare them with lamivudine + tenofovir (3TC + TDF). METHODS: Three hundred fifty-two HIV-1 B-subtype pol sequences from 42 FTC + TDF-treated patients, 40 3TC + TDF-treated patients, and 270 patients treated with 3TC plus another nucleoside reverse transcriptase inhibitor (but not TDF). All patients never received FTC, 3TC, and TDF in their previous therapeutic regimen. 3TC/FTC ± TDF resistance was investigated using in vitro selection experiments and docking simulations. RESULTS: The M184V mutation is less prevalent in FTC + TDF-treated patients than in 3TC + TDF-treated, and 3TC-treated/TDF-naive patients (14.3% versus 40.0%, P = 0.01 and 55.6%, P < 0.001). Multivariable analysis shows that factors correlated with a lower probability of M184V emergence at failure were the use of FTC compared with 3TC [odds ratio (OR): 0.32 (95% confidence interval (CI): 0.10 to 0.99), P = 0.04], the use of boosted protease inhibitor, and the use of TDF [OR: 0.20 (95% CI: 0.11 to 0.37), P < 0.001, and OR: 0.47 (95%CI: 0.22 to 1.01), P = 0.05, respectively]. In vitro selection experiments and docking analysis show that other reverse transcriptase (RT) mutations, even localized in RT connection domain, can be selected by 3TC + TDF or FTC + TDF in M184V absence and can affect RT affinity for 3TC/FTC and/or TDF. CONCLUSIONS: Our study shows lower rates of M184V development in FTC + TDF regimens versus 3TC + TDF and suggests a potential role of boosted protease inhibitors and TDF in delaying the M184V emergence. Novel RT mutational patterns, more complex than currently known, can contribute to 3TC, FTC, and TDF resistance.
Authors: Rochelle P Walensky; Paul E Sax; Yoriko M Nakamura; Milton C Weinstein; Pamela P Pei; Kenneth A Freedberg; A David Paltiel; Bruce R Schackman Journal: Ann Intern Med Date: 2013-01-15 Impact factor: 25.391
Authors: Benjamin H Chi; Albert Mwango; Mark J Giganti; Izukanji Sikazwe; Crispin Moyo; Linnaea Schuttner; Lloyd B Mulenga; Carolyn Bolton-Moore; Namwinga T Chintu; Robert Sheneberger; Elizabeth M Stringer; Jeffrey S A Stringer Journal: J Acquir Immune Defic Syndr Date: 2011-12-15 Impact factor: 3.731
Authors: Hugues Charest; Florence Doualla-Bell; Régis Cantin; Donald G Murphy; Linda Lemieux; Bluma Brenner; Isabelle Hardy; Daniela Moisi; Ernest Lo; Jean-Guy Baril; Mark A Wainberg; Michel Roger; Cécile Tremblay Journal: PLoS One Date: 2014-10-08 Impact factor: 3.240
Authors: Francesc Homar; Virginia Lozano; Juan Martínez-Gómez; Itziar Oyagüez; Antonio Pareja; Antoni Payeras; Joaquín Serrano; Carmen Carratalá; Miguel Angel Casado Journal: Health Econ Rev Date: 2012-09-03
Authors: Alexandra U Scherrer; Jürg Böni; Sabine Yerly; Thomas Klimkait; Vincent Aubert; Hansjakob Furrer; Alexandra Calmy; Matthias Cavassini; Luigia Elzi; Pietro L Vernazza; Enos Bernasconi; Bruno Ledergerber; Huldrych F Günthard Journal: PLoS One Date: 2012-11-26 Impact factor: 3.240