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

Hans-Jürgen Stellbrink, Eric Le Fevre, Andrew Carr, Michael S. Saag, Geoffrey Mukwaya, Silvia Nozza, Srinivas Rao Valluri, Manoli Vourvahis, Alex R. Rinehart, Lynn McFadyen, Carl Fichtenbaum, Andrew Clark, Charles Craig, Annie F. Fang, Jayvant Heera

Research output: Contribution to journalArticle

Abstract

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 1000copies/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 150mg 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 50copies/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 50copies/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.
Original languageEnglish
Pages (from-to)1229 - 1238
Number of pages10
JournalAIDS
Volume30
Issue number8
DOIs
Publication statusPublished - May 15 2016

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Tenofovir
Ritonavir
HIV-1
Tropism
RNA
Clinical Trials Data Monitoring Committees
Pharmaceutical Preparations
Body Fat Distribution
Bone Remodeling
United States Food and Drug Administration
maraviroc
Darunavir
Emtricitabine
Bone Density

Keywords

  • darunavir
  • emtricitabine
  • HIV-1
  • maraviroc
  • nucleos(t)ide-sparing regimen
  • tenofovir
  • treatment-naive

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

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.

In: AIDS, Vol. 30, No. 8, 15.05.2016, p. 1229 - 1238.

Research output: Contribution to journalArticle

Stellbrink, H-J, Le Fevre, E, Carr, A, Saag, MS, Mukwaya, G, Nozza, S, Valluri, SR, Vourvahis, M, Rinehart, AR, McFadyen, L, Fichtenbaum, C, Clark, A, Craig, C, Fang, AF & Heera, J 2016, 'Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment', AIDS, vol. 30, no. 8, pp. 1229 - 1238. https://doi.org/10.1097/QAD.0000000000001058
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. In: AIDS. 2016 ; Vol. 30, No. 8. pp. 1229 - 1238.
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abstract = "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 1000copies/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 150mg 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 50copies/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 50copies/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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T1 - Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment

AU - Stellbrink, Hans-Jürgen

AU - Le Fevre, Eric

AU - Carr, Andrew

AU - Saag, Michael S.

AU - Mukwaya, Geoffrey

AU - Nozza, Silvia

AU - Valluri, Srinivas Rao

AU - Vourvahis, Manoli

AU - Rinehart, Alex R.

AU - McFadyen, Lynn

AU - Fichtenbaum, Carl

AU - Clark, Andrew

AU - Craig, Charles

AU - Fang, Annie F.

AU - Heera, Jayvant

PY - 2016/5/15

Y1 - 2016/5/15

N2 - 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 1000copies/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 150mg 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 50copies/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 50copies/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.

AB - 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 1000copies/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 150mg 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 50copies/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 50copies/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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KW - emtricitabine

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KW - maraviroc

KW - nucleos(t)ide-sparing regimen

KW - tenofovir

KW - treatment-naive

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