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Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment

OBJECTIVE: The aim of this study was to evaluate the efficacy of maraviroc along with darunavir/ritonavir, all once daily, for the treatment of antiretroviral-naive HIV-1 infected individuals. DESIGN: MODERN was a multicentre, double-blind, noninferiority, phase III study in HIV-1 infected, antiretr...

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Autores principales: Stellbrink, Hans-Jürgen, Le Fevre, Eric, Carr, Andrew, Saag, Michael S., Mukwaya, Geoffrey, Nozza, Silvia, Valluri, Srinivas Rao, Vourvahis, Manoli, Rinehart, Alex R., McFadyen, Lynn, Fichtenbaum, Carl, Clark, Andrew, Craig, Charles, Fang, Annie F., Heera, Jayvant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856180/
https://www.ncbi.nlm.nih.gov/pubmed/26854810
http://dx.doi.org/10.1097/QAD.0000000000001058
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author Stellbrink, Hans-Jürgen
Le Fevre, Eric
Carr, Andrew
Saag, Michael S.
Mukwaya, Geoffrey
Nozza, Silvia
Valluri, Srinivas Rao
Vourvahis, Manoli
Rinehart, Alex R.
McFadyen, Lynn
Fichtenbaum, Carl
Clark, Andrew
Craig, Charles
Fang, Annie F.
Heera, Jayvant
author_facet Stellbrink, Hans-Jürgen
Le Fevre, Eric
Carr, Andrew
Saag, Michael S.
Mukwaya, Geoffrey
Nozza, Silvia
Valluri, Srinivas Rao
Vourvahis, Manoli
Rinehart, Alex R.
McFadyen, Lynn
Fichtenbaum, Carl
Clark, Andrew
Craig, Charles
Fang, Annie F.
Heera, Jayvant
author_sort Stellbrink, Hans-Jürgen
collection PubMed
description OBJECTIVE: The aim of this study was to evaluate the efficacy of maraviroc along with darunavir/ritonavir, all once daily, for the treatment of antiretroviral-naive HIV-1 infected individuals. DESIGN: MODERN was a multicentre, double-blind, noninferiority, phase III study in HIV-1 infected, antiretroviral-naive adults with plasma HIV-1 RNA at least 1000 copies/ml and no evidence of reduced susceptibility to study drugs. METHODS: At screening, participants were randomized 1 : 1 to undergo either genotypic or phenotypic tropism testing. Participants with CCR5-tropic HIV-1 were randomized 1 : 1 to receive maraviroc 150 mg once daily or tenofovir/emtricitabine once daily each with darunavir/ritonavir once daily for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies/ml (Food and Drug Administration snapshot algorithm) at Week 48. A substudy evaluated bone mineral density, body fat distribution and serum bone turnover markers. RESULTS: Seven hundred and ninety-seven participants were dosed (maraviroc, n = 396; tenofovir/emtricitabine, n = 401). The Data Monitoring Committee recommended early study termination due to inferior efficacy in the maraviroc group. At Week 48, the proportion of participants with HIV-1 RNA less than 50 copies/ml was 77.3% for maraviroc and 86.8% for tenofovir/emtricitabine [difference of −9.54% (95% confidence interval: −14.83 to −4.24)]. More maraviroc participants discontinued for lack of efficacy, which was not associated with non-R5 tropism or resistance. Discontinuations for adverse events, Category C events, Grade 3/4 adverse events and laboratory abnormalities were similar between groups. CONCLUSION: A once-daily nucleos(t)ide-sparing two-drug regimen of maraviroc and darunavir/ritonavir was inferior to a three-drug regimen of tenofovir/emtricitabine and darunavir/ritonavir in antiretroviral-naive adults.
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spelling pubmed-48561802016-05-23 Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment Stellbrink, Hans-Jürgen Le Fevre, Eric Carr, Andrew Saag, Michael S. Mukwaya, Geoffrey Nozza, Silvia Valluri, Srinivas Rao Vourvahis, Manoli Rinehart, Alex R. McFadyen, Lynn Fichtenbaum, Carl Clark, Andrew Craig, Charles Fang, Annie F. Heera, Jayvant AIDS Clinical Science OBJECTIVE: The aim of this study was to evaluate the efficacy of maraviroc along with darunavir/ritonavir, all once daily, for the treatment of antiretroviral-naive HIV-1 infected individuals. DESIGN: MODERN was a multicentre, double-blind, noninferiority, phase III study in HIV-1 infected, antiretroviral-naive adults with plasma HIV-1 RNA at least 1000 copies/ml and no evidence of reduced susceptibility to study drugs. METHODS: At screening, participants were randomized 1 : 1 to undergo either genotypic or phenotypic tropism testing. Participants with CCR5-tropic HIV-1 were randomized 1 : 1 to receive maraviroc 150 mg once daily or tenofovir/emtricitabine once daily each with darunavir/ritonavir once daily for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies/ml (Food and Drug Administration snapshot algorithm) at Week 48. A substudy evaluated bone mineral density, body fat distribution and serum bone turnover markers. RESULTS: Seven hundred and ninety-seven participants were dosed (maraviroc, n = 396; tenofovir/emtricitabine, n = 401). The Data Monitoring Committee recommended early study termination due to inferior efficacy in the maraviroc group. At Week 48, the proportion of participants with HIV-1 RNA less than 50 copies/ml was 77.3% for maraviroc and 86.8% for tenofovir/emtricitabine [difference of −9.54% (95% confidence interval: −14.83 to −4.24)]. More maraviroc participants discontinued for lack of efficacy, which was not associated with non-R5 tropism or resistance. Discontinuations for adverse events, Category C events, Grade 3/4 adverse events and laboratory abnormalities were similar between groups. CONCLUSION: A once-daily nucleos(t)ide-sparing two-drug regimen of maraviroc and darunavir/ritonavir was inferior to a three-drug regimen of tenofovir/emtricitabine and darunavir/ritonavir in antiretroviral-naive adults. Lippincott Williams & Wilkins 2016-05-15 2016-05-03 /pmc/articles/PMC4856180/ /pubmed/26854810 http://dx.doi.org/10.1097/QAD.0000000000001058 Text en Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0
spellingShingle Clinical Science
Stellbrink, Hans-Jürgen
Le Fevre, Eric
Carr, Andrew
Saag, Michael S.
Mukwaya, Geoffrey
Nozza, Silvia
Valluri, Srinivas Rao
Vourvahis, Manoli
Rinehart, Alex R.
McFadyen, Lynn
Fichtenbaum, Carl
Clark, Andrew
Craig, Charles
Fang, Annie F.
Heera, Jayvant
Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment
title Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment
title_full Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment
title_fullStr Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment
title_full_unstemmed Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment
title_short Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment
title_sort once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial hiv-1 treatment
topic Clinical Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856180/
https://www.ncbi.nlm.nih.gov/pubmed/26854810
http://dx.doi.org/10.1097/QAD.0000000000001058
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