Comparative Trial Of Maraviroc Versus Emtricitabine/Tenofovir Both With Darunavir/Ritonavir In Antiretroviral-Naive Patients Infected With CCR5 Tropic HIV 1 (MODERN)

A Multicenter, Randomized, Double-Blind, Comparative Trial Of Maraviroc + Darunavir/Ritonavir Versus Emtricitabine/Tenofovir + Darunavir/Ritonavir For The Treatment Of Antiretroviral-Naive Hiv-Infected Patients With Ccr5-Tropic Hiv-1

The purpose of this study is to assess whether maraviroc administered once daily is non-inferior to emtricitabine/tenofovir also administered once daily each in combination with darunavir/ritonavir in the treatment of antiretroviral-naive patients as evaluated at Week 48 of treatment.

Study Overview

• Status: Terminated
• Conditions: HIV-1
• Intervention / Treatment: Drug: Maraviroc; Drug: darunavir/ritonavir 800/100 mg; Drug: placebo for maraviroc; Drug: Emtricitabine/tenofovir; Drug: placebo for emtricitabine/tenofovir

Detailed Description

The study was terminated on October 8, 2013 following a preliminary review of the Week 48 primary efficacy data by the study's external independent Data Monitoring Committee (DMC). The DMC assessed the data as demonstrating significant differences between the treatment arms in virologic responses and failures. The DMC recommended and the Sponsor concurred that the study be terminated because of the inferior efficacy of the Maraviroc arm as compared to the comparator arm (Emtricitabine/Tenofovir).

• Study Type: Interventional
• Enrollment (Actual): 813
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • East Sydney Doctors
    • Darlinghurst, New South Wales, Australia, 2010
      • Holdsworth House General Practice
    • Surry Hills, New South Wales, Australia, 2010
      • Taylor Square Private Clinic
  • Queensland
    • Brisbane, Queensland, Australia, 4000
      • Brisbane Sexual Health and HIV Service
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • Melbourne Sexual Health Centre
    • Melbourne, Victoria, Australia, 3004
      • Clinical Research Unit, Infectious Diseases
• Austria
  • Wien, Austria, 1090
    • AKH Wien Universitaetsklinik fuer Dermatologie
• Belgium
  • Antwerpen, Belgium, B-2000
    • Instituut voor Tropische Geneeskunde
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Brussels, Belgium, 1000
    • C.H.U. St-Pierre
  • Bruxelles, Belgium, 1070
    • Hopital Universitaire Erasme
  • Gent, Belgium, B-9000
    • Universitair Ziekenhuis Gent
  • Liege, Belgium, 4000
    • C.H.U. Sart-Tilman
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Vancouver ID Research and Care Centre Society
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Ottawa, Ontario, Canada, K1H 7W9
      • The Ottawa Hospital-Riverside Campus
    • Toronto, Ontario, Canada, M5G 1K2
      • Maple Leaf Research / Maple Leaf Medical Clinic
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network / Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 5B1
      • Clinique Medicale du Quartier Latin
    • Montreal, Quebec, Canada, H2L 4P9
      • Clinique Médicale L'Actuel
• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital, Infektionsmedicinsk afd.
  • Koebenhavn OE, Denmark, 2100
    • Rigshospitalet, Epidemiklinikken
  • Odense, Denmark, 5000
    • Odense Universitetshospital
• Finland
  • Helsinki, Finland, 00250
    • Infektiosairauksien poliklinikka,HUS Auroran sairaala, rakennus 5, 1. krs
• France
  • Bordeaux cedex, France, 33075
    • Hôpital Saint-André
  • Creteil, France, 94000
    • Hopital Henri Mondor
  • LYON Cedex 4, France, 69317
    • Hôpital de la Croix Rousse
  • Le Kremlin Bicetre, France, 94275
    • Hôpital Bicêtre
  • Montpellier, France, 34295
    • Hopital Gui de Chauliac
  • Nantes, France, 44035
    • CHU de Nantes - Hôtel Dieu
  • Paris, France, 75013
    • Hôpital de la Pitié Salpêtrière
  • Paris, France, 75020
    • Hopital Tenon, Service des Maladies Infectieuses
  • Paris Cedex 10, France, 75475
    • Hôpital Saint-Louis
  • Strasbourg Cedex, France, 67091
    • Nouvel Hôpital Civil
  • Tourcoing, France, 59208
    • Centre Hospitalier de Tourcoing
  • Cedex 02
    • Orleans, Cedex 02, France, 45067
      • CHR d'Orléans La Source
  • Cedex 12
    • Paris, Cedex 12, France, 75571
      • Hopital Saint Antoine
  • Cedex 18
    • Paris, Cedex 18, France, 75877
      • Hôpital Bichat
• Germany
  • Berlin, Germany, 10243
    • Praxis Christiane Cordes
  • Berlin, Germany, 10243
    • Studiengesellschaft mbH Gubener 37
  • Berlin, Germany, 12157
    • EPIMED - Gesellschaft fuer epidemiologische und klinische Forschung in der Medizin mbH
  • Bonn, Germany, 53127
    • Universitaetsklinikum Bonn, Immunologische Ambulanz HIV
  • Frankfurt am Main, Germany, 60590
    • Klinikum der J.W. Goethe-Universitaet, Medizinische Klinik II
  • Frankfurt am Main, Germany, 60596
    • Infektioresearch GmbH & Co. KG
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf
  • Hamburg, Germany, 20099
    • Ifi - Studien und Projekte GmbH
  • Hamburg, Germany, 20146
    • ICH - Study - Center GmbH & Co. KG
  • Koeln, Germany, 50937
    • Klinikum der Universitaet zu Koeln, Klinik I fuer Innere Medizin
  • Muenchen, Germany, 80335
    • MUC Research Group GbR
  • Muenchen, Germany, 80336
    • Ludwig-Maximilians-Universitaet, Medizinische Poliklinik - Klinikum Innenstadt
• Hungary
  • Budapest, Hungary, 1097
    • Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet
• Italy
  • Milano, Italy, 20127
    • Ospedale San Raffaele
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
• Poland
  • Bydgoszcz, Poland, 85-030
    • Wojewodzki Szpital Obserwacyjno - Zakazny im. Tadeusza Browicza
  • Warszawa, Poland, 01-201
    • SPZOZ Wojewodzki Szpital Zakazny
  • Wroclaw, Poland, 50-220
    • EMC Instytut Medyczny S.A. Przychodnia przy ul. Lowieckiej
• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Prof. Doutor Fernando Fonseca E.P.E.
  • Lisboa, Portugal, 1169-050
    • Centro Hospitalar de Lisboa - Zona Central - Hospital Santo António Capuchos
  • Lisboa, Portugal, 1649-035
    • Hospital Sta. Maria
  • Porto, Portugal, 4200-319
    • Hospital Sao Joao
• Puerto Rico
  • Bayamon, Puerto Rico, 00959
    • Innovative Care PSC
  • Ponce, Puerto Rico, 00717
    • Ararat Research Center
  • Rio Piedras, Puerto Rico, 00935
    • Medical Center University Hospital
  • Rio Piedras, Puerto Rico, 00935
    • University of Puerto Rico Medical Sciences Campus
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Hope Clinical Research
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia - Hospital Provincial
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28046
    • Hospital Universitario de La Paz
  • Sevilla, Spain, 41007
    • Hospital Universitario Virgen De La Macarena
  • Barcelona
    • L´hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
• Sweden
  • Goteborg, Sweden, 416 85
    • SU Ostra sjukhuset, Infektionsmottagningen
  • Malmo, Sweden, 205 02
    • Skanes Universitetssjukhus
  • Stockholm, Sweden, 141 86
    • Karolinska Universitetssjukhuset Huddinge
  • Stockholm, Sweden, 118 83
    • Sodersjukhuset, Venhalsan
• Switzerland
  • Basel, Switzerland, 4031
    • Universitaetsspital Basel Infektiologie und Spitalhygiene
  • Bern, Switzerland, 3010
    • Inselspital Universitaetsklinik fuer Infektiologie
  • St. Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
  • Zurich, Switzerland, 8091
    • Universitätsspital Zürich
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Dept of Sexual Health & HIV Medicine
  • Brighton, United Kingdom, BN2 1ES
    • HIV Research Department, Elton John Centre
  • Edinburgh, United Kingdom, EH4 2XU
    • Regional Infectious Diseases Unit
  • London, United Kingdom, SE18 4QH
    • Queen Elizabeth Hospital
  • London, United Kingdom, SW10 9NH
    • St Stephen's Centre, Chelsea and Westminster Hospital NHS Foundation Trust
  • London, United Kingdom, E1 1BB
    • Grahame Hayton Unit, Ambrose King Centre, Royal London Hospital,
  • London, United Kingdom, NW3 2QG
    • Ian Charleson Day Centre, Royal Free Hospital
  • London, United Kingdom, WC1E 6AU
    • Centre for Sexual Health & HIV Research, University College London
  • Manchester, United Kingdom, M8 5RB
    • Department of Infectious Diseases & Tropical Medicine, Pennine Acute Trust Hospitals
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham - 1917 Research Clinic
    • Hobson City, Alabama, United States, 36201
      • Health Services Center
  • California
    • Hayward, California, United States, 94545
      • Kaiser Permanente
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90069
      • Dr. Anthony Mills, MD, Inc.
    • Newport Beach, California, United States, 92663
      • Orange Coast Medical Group
    • Palm Springs, California, United States, 92262
      • Desert Oasis Healthcare Medical Group
    • Sacramento, California, United States, 95814
      • University of California Davis Research
    • Sacramento, California, United States, 95817
      • TICON I Research Clinic (DEXA Scan only)
    • Sacramento, California, United States, 95825
      • Kaiser Hospital Sacramento
    • San Francisco, California, United States, 94105
      • Synarc Inc.
    • San Francisco, California, United States, 94118
      • Investigational Drugs Pharmacy
    • San Francisco, California, United States, 94118
      • Kaiser Permanente - Clinical Trials Unit
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Santa Clara
    • Union City, California, United States, 94587
      • Kaiser Permanente
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver - University of Colorado Hospital
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
    • New Haven, Connecticut, United States, 06504
      • Yale - New Haven Hospital Nathan Smith Clinic
    • Norwalk, Connecticut, United States, 06851
      • Circle Care Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Faculty Associates
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, PC
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Fort Lauderdale, Florida, United States, 33311
      • Broward Health - Comprehensive Care Center
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33143
      • Miami Research Associates
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Miami, Florida, United States, 33136
      • UMHC/Sylvester Comprehensive Cancer Center
    • Miami, Florida, United States, 33136
      • University of Miami AIDS Clinical Research Unit
    • Miami, Florida, United States, 33137
      • Community AIDS Resource Inc dba Care Resource
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Pensacola, Florida, United States, 32504
      • Infectious Diseases Associates of Northwest Florida, PA
    • Tampa, Florida, United States, 33614
      • Infectious Disease Research Institute, Inc.
    • Tampa, Florida, United States, 33067
      • St. Joseph's Hospital Diagnostic Center
    • Tampa, Florida, United States, 33602
      • University of South Florida Health-HIV Clinical Research Unit
    • Tampa, Florida, United States, 33614
      • Osteoporosis Care Center
    • Tampa, Florida, United States, 33614
      • Quest Diagnostic Laboratory
    • Wilton Manors, Florida, United States, 33305
      • Rowan Tree Medical, PA
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • AIDS Research Consortium of Atlanta
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Decatur, Georgia, United States, 30033
      • DeKalb Medical Diagnostic Breast Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University/NMH
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa, University of Hospitals and Clinics - Division of Infectious Disease
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Infectious Diseases Clinical Research
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center, PC
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48201
      • Wayne State University
    • Detroit, Michigan, United States, 48201
      • University Physicians Group
    • East Lansing, Michigan, United States, 48824
      • Michigan State University College of Osteopathic Medicine - Department of Internal Medicine
    • East Lansing, Michigan, United States, 48825
      • Biomedical and Health Institutional Review Board
    • Lansing, Michigan, United States, 48911
      • Ingham County Health Department
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Kansas City Free Health Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • University of Nebraska Medical Center
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore University Medical Center
    • Neptune, New Jersey, United States, 07754
      • Jersey Shore University Medical Center
    • Neptune, New Jersey, United States, 07754
      • Brandywine Common
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
  • New York
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center
    • New York, New York, United States, 10022
      • Research Across America
    • New York, New York, United States, 10003
      • Beth Israel Medical Center - AIDS Clinical Trials Unit
    • New York, New York, United States, 10018
      • AIDS Community Research Initiative of America (ACRIA)
    • New York, New York, United States, 10107
      • Dr. Howard A. Grossman, M.D.
    • Rochester, New York, United States, 14607
      • Aids Care
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • I.D. Consultants, P.A.
    • Greenville, North Carolina, United States, 27834
      • (DEXA Scan Facility) East Carolina University Brody Outpatient Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University Division of Infectious Diseases
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati - Department of Internal Medicine
    • Toledo, Ohio, United States, 43614
      • The University of Toledo Medical Center
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes and Endocrine Center
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center at Dallas
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants, PA
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Research Access Network
    • Houston, Texas, United States, 77098
      • The Office of Dr. Gordon E. Crofoot, M.D., PA
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Plasma HIV-1 RNA equal to or greater than 1,000 copies/mL measured at the Screening Visit.
• CD4 count equal to or greater than 100 cells/mm3 at Screening.
• Have only R5 HIV 1 at Screening as verified by a randomized tropism assay.

Exclusion Criteria:

• Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any time.
• Any evidence of genotypic/phenotypic resistance to darunavir, tenofovir, and emtricitabine.
• CXCR4 using virus detected using randomized tropism determination or repeated failure to obtain an interpretable tropism result.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maraviroc; Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.	Drug: Maraviroc; Maraviroc tablet 150 mg once daily for 96 weeks.; Other Names: Selzentry, Celsentri; Drug: darunavir/ritonavir 800/100 mg; darunavir/ritonavir 800/100 mg; Drug: placebo for maraviroc; placebo for maraviroc; Other Names: Selzentry, Celsentri
Active Comparator: Emtricitabine/tenofovir; Emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.	Drug: Emtricitabine/tenofovir; Emtricitabine/tenofovir tablet 200/300 mg once daily for 96 weeks.; Other Names: Truvada; Drug: placebo for emtricitabine/tenofovir; placebo for emtricitabine/tenofovir; Other Names: Truvada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL.	The proportion of participants who achieved HIV-1 RNA <50 copies/mL at week 48 was assessed according to Food and Drug Administration's (FDA's) Missing, Switch, Discontinuation'=Failure (MSDF) Snapshot algorithm. The algorithm used the plasma HIV-1 RNA in the Week 48 visit window, followed the "virology-first principle" and considers a participant who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse Events (AE).	Number of participants with treatment-emergent non serious AEs	Week 96
Number of Participants With Grade 3 or 4 AEs	Number of participants with grade 3 or 4 AEs are presented here.	Week 96
Number of Participants Who Discontinued Due to AEs	Number of participants who discontinued due to AEs are reported here. Three participants (two from the MVC+DRV/r arm and one from the FTC/TDF+DRV/r arm) were not considered as discontinued due to AE because other reasons for discontinuation were prioritized for these participants.	Week 96
Number of Treatment-related AEs	Number of treatment-related AEs are presented here.	Week 96
Number of Participants With Treatment-emergent Serious Adverse Events	Total number of participants with treatment-emergent serious adverse events are reported	Week 96
Number of Participants With Abnormal Laboratory Values	Number of participants with laboratory abnormalities are reported	Week 96
Severity of Abnormal Laboratory Values	Number of participants who had clinically significant laboratory abnormalities of Grade 3 and Grade 4 according to DAIDS. Abnormality incidence of highest grade was reported for a labcode for each individual participant.	Week 96
The Relationship Between the Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL at the Week 48 and the Screening Tropism Test (Genotype Test or ESTA).	The relationship of the proportion of participants achieving HIV-1 RNA <50 copies/mL at Week 48 with the screening tropism test for the MVC containing regimen was analyzed. Virologic response for a participant at Week 48 was derived using the FDA's Snapshot MSDF algorithm. Difference in proportions of patients with plasma HIV-1 RNA <50 copies/mL at week 48 between the maraviroc and the emtricitabine/tenofovir treatment arms, with two-sided 95% confidence interval, among patients who are R5 by genotype (including some who were originally randomized to ESTA and are R5 by genotype upon retesting), were calculated via the Maximum Likelihood method. The estimate was adjusted for the screening plasma HIV RNA level (<100,000 vs. ≥100,000) copies/mL via the Mantel Haenszel (MH) method.	Week 48
Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF).	Per the protocol participants who meet the following criteria were regarded as PDTFs requiring a confirmatory plasma HIV-1 RNA determination: • Decrease in plasma HIV-1 RNA <1 log10 from baseline after Week 4 unless plasma HIV-1 RNA is <50 copies/mL, or • Plasma HIV-1 RNA >1.0 log10 above the nadir value after Week 4 where the nadir is the lowest plasma HIV-1 RNA concentration, or • Plasma HIV-1 RNA ≥50 copies/mL at any time after Week 24, or • Plasma HIV-1 RNA ≥50 copies/mL after suppression to <50 copies/mL on two consecutive visits, or • Decrease in plasma HIV-1 RNA ≤2 log10 from baseline on or after Week 12 unless plasma HIV-1 RNA is <400 copies/mL. Decrease in plasma HIV-1 RNA ≤2 log10 from baseline on or after Week 12 unless plasma HIV-1 RNA is <50 copies/mL (before August 30 2012) or <400 copies/mL (after August 30 2012).	Week 48
Tropism Change Between Screening or Baseline and PDTF	For participants meeting the PDTF criteria, tropism was assessed using the original randomized and alternate assays (ie, both genotype testing and ESTA). Data reported here corresponds to the timepoint at or after PDTF.	Week 48
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria.	For participants meeting the PDTF criteria, viral resistance to maraviroc for maraviroc treated participants was assessed in patients with R5 virus at failure. The resistance level is calculated by reference to a laboratory strain of virus that is analyzed in parallel with the clinical isolate to identify 50% inhibitory concentrations (IC50). The maximal percent inhibition is the percent inhibition that is achieved in a titration of the drug at high concentrations when the addition of more drug does not result in increased inhibition. Maximal percent inhibition is obtained in the same way as the titration for IC50, but the key measure is of the plateau height of percent inhibition, where increased concentration of maraviroc does not result in additional inhibition. This is consistent with the virus developing some ability to use maraviroc-bound CCR5 for entry. A significant change in IC50 is not required for this mechanism.	Week 48
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria	For participants meeting the PDTF criteria, viral resistance (both genotypic and phenotypic) to NRTI, NNRTI, and PI's were assessed at Baseline and on-treatment. The assessment was performed using the overall (i.e. net) susceptibility score provided using the PhenoSense GT assay. The number of participants with successful assessments were 15/17 for the MVC+DRV/r arm and 3/3 for the FTC/TDF+DRV/r arm.	Week 48
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 4 (CD4, Cell/mm^3)	The differences in the magnitude of changes in CD4+ at Baseline and at Week 48 for maraviroc versus emtricitabine/tenofovir were compared.	Baseline, Week 48
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%)	The differences in the magnitude of changes in CD4+ from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.	Baseline, Week 48
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 8 (CD8, Cell/mm^3)	The differences in the magnitude of changes in CD8+ cell counts from baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.	Baseline, Week 48
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%)	The differences in the magnitude of changes in CD8+ cell counts from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.	Baseline, Week 48
Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48	The differences in the magnitude of changes in CD4+/CD8+ ratio from Baseline through Weeks 48 for maraviroc versus emtricitabine/tenofovir were compared.	Baseline, Week 48
Changes in Peripheral Fat Distribution Using Dual Energy X-ray Absorptiometry [DEXA] Scan From Baseline and at Week 48.	A sub-study was conducted in which the participants underwent whole-body DEXA scans to evaluate peripheral fat tissue estimates for left and right arms and legs and truncal fat mass and truncal lean mass. Truncal abdominal fat were estimated from the DEXA scan field set on the torso. The effects on estimates of fat mass and lean mass were addressed by providing LSMs of change from baseline.	Week 48
Changes in Trunk to Limb Fat Distribution Using DEXA Scan From Baseline and at Week 48	A sub-study was conducted in which the participants underwent whole-body DEXA scans to evaluate peripheral fat tissue estimates for left and right arms and legs and truncal fat mass and truncal lean mass. Truncal abdominal fat were estimated from the DEXA scan field set on the torso. The effects on estimates of fat mass and lean mass were addressed by providing LSMs of change from baseline.	Week 48
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Total Hip BMD	Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from baseline bone mineral density of the lumbar spine (L1-L4), left total hip and femoral neck as measured by the DEXA scan.	Week 48
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Femoral Neck BMD	Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from Baseline bone mineral density femoral neck as measured by the DEXA scan.	Week 48
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - AP Lumbar Spine (L1 - L4) BMD	Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from baseline bone mineral density of the lumbar spine (L1-L4) as measured by the DEXA scan.	Week 48
Change in Bone Turnover Markers From Baseline and at Week 48 - Blood Osteocalcin	Bone turnover marker, osteocalcin, was collected in the subset of participants participating in the DEXA scan sub-study.	Week 48
Change in Bone Turnover Markers From Baseline and at Week 48 - Type 1 Collagen Peptide (CTX-1)	Bone turnover marker, C-telopeptide of type 1 collagen (CTx), was collected in the subset of participants participating in the DEXA scan sub-study.	Week 48

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: April 27, 2011
• First Submitted That Met QC Criteria: April 28, 2011
• First Posted (Estimate): May 2, 2011

Study Record Updates

• Last Update Posted (Estimate): January 14, 2016
• Last Update Submitted That Met QC Criteria: December 11, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Double-blind; trial; maraviroc; comparative; versus; emtricitabine/tenofovir; both with darunavir/ritonavir; antiretroviral-naive; Ccr5 tropic; Hiv 1; patients.
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Tenofovir; Emtricitabine; Ritonavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Maraviroc; Darunavir
• Other Study ID Numbers: A4001095; 2010-021785-30 (EudraCT Number)