Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study
Background. Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1–infected subjects with genotypic evidence of RAL re...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563307/ https://www.ncbi.nlm.nih.gov/pubmed/23225901 http://dx.doi.org/10.1093/infdis/jis750 |
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author | Eron, Joseph J. Clotet, Bonaventura Durant, Jacques Katlama, Christine Kumar, Princy Lazzarin, Adriano Poizot-Martin, Isabelle Richmond, Gary Soriano, Vincent Ait-Khaled, Mounir Fujiwara, Tamio Huang, Jenny Min, Sherene Vavro, Cindy Yeo, Jane Walmsley, Sharon L. Cox, Joseph Reynes, Jacques Morlat, Philippe Vittecoq, Daniel Livrozet, Jean-Michel Fernández, Pompeyo Viciana Gatell, Jose M. DeJesus, Edwin DeVente, Jerome Lalezari, Jacob P. McCurdy, Lewis H. Sloan, Louis A. Young, Benjamin LaMarca, Anthony Hawkins, Trevor |
author_facet | Eron, Joseph J. Clotet, Bonaventura Durant, Jacques Katlama, Christine Kumar, Princy Lazzarin, Adriano Poizot-Martin, Isabelle Richmond, Gary Soriano, Vincent Ait-Khaled, Mounir Fujiwara, Tamio Huang, Jenny Min, Sherene Vavro, Cindy Yeo, Jane Walmsley, Sharon L. Cox, Joseph Reynes, Jacques Morlat, Philippe Vittecoq, Daniel Livrozet, Jean-Michel Fernández, Pompeyo Viciana Gatell, Jose M. DeJesus, Edwin DeVente, Jerome Lalezari, Jacob P. McCurdy, Lewis H. Sloan, Louis A. Young, Benjamin LaMarca, Anthony Hawkins, Trevor |
author_sort | Eron, Joseph J. |
collection | PubMed |
description | Background. Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1–infected subjects with genotypic evidence of RAL resistance. Methods. Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log(10) copies/mL from baseline or was <400 copies/mL. Results. A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen. Conclusion. Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL. |
format | Online Article Text |
id | pubmed-3563307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35633072013-02-04 Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study Eron, Joseph J. Clotet, Bonaventura Durant, Jacques Katlama, Christine Kumar, Princy Lazzarin, Adriano Poizot-Martin, Isabelle Richmond, Gary Soriano, Vincent Ait-Khaled, Mounir Fujiwara, Tamio Huang, Jenny Min, Sherene Vavro, Cindy Yeo, Jane Walmsley, Sharon L. Cox, Joseph Reynes, Jacques Morlat, Philippe Vittecoq, Daniel Livrozet, Jean-Michel Fernández, Pompeyo Viciana Gatell, Jose M. DeJesus, Edwin DeVente, Jerome Lalezari, Jacob P. McCurdy, Lewis H. Sloan, Louis A. Young, Benjamin LaMarca, Anthony Hawkins, Trevor J Infect Dis Major Articles and Brief Reports Background. Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1–infected subjects with genotypic evidence of RAL resistance. Methods. Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log(10) copies/mL from baseline or was <400 copies/mL. Results. A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen. Conclusion. Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL. Oxford University Press 2013-03-01 2012-12-07 /pmc/articles/PMC3563307/ /pubmed/23225901 http://dx.doi.org/10.1093/infdis/jis750 Text en © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Major Articles and Brief Reports Eron, Joseph J. Clotet, Bonaventura Durant, Jacques Katlama, Christine Kumar, Princy Lazzarin, Adriano Poizot-Martin, Isabelle Richmond, Gary Soriano, Vincent Ait-Khaled, Mounir Fujiwara, Tamio Huang, Jenny Min, Sherene Vavro, Cindy Yeo, Jane Walmsley, Sharon L. Cox, Joseph Reynes, Jacques Morlat, Philippe Vittecoq, Daniel Livrozet, Jean-Michel Fernández, Pompeyo Viciana Gatell, Jose M. DeJesus, Edwin DeVente, Jerome Lalezari, Jacob P. McCurdy, Lewis H. Sloan, Louis A. Young, Benjamin LaMarca, Anthony Hawkins, Trevor Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study |
title | Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study |
title_full | Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study |
title_fullStr | Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study |
title_full_unstemmed | Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study |
title_short | Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects With Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study |
title_sort | safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant hiv type 1 infection: 24-week results of the viking study |
topic | Major Articles and Brief Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563307/ https://www.ncbi.nlm.nih.gov/pubmed/23225901 http://dx.doi.org/10.1093/infdis/jis750 |
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