Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine (MERIT)

A Multicenter, Randomized, Double-Blind, Comparative Trial Of A Novel CCR5 Antagonist, UK-427,857, In Combination With Zidovudine/Lamivudine Versus Efavirenz In Combination With Zidovudine/Lamivudine For The Treatment Of Antiretroviral-Naive HIV-1 Infected Subjects

Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients, maraviroc (UK-427,857) given as monotherapy for 10 days reduced HIV-1 viral load by up to 1.6 log, consistent with currently available agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at 300 mg twice daily. No significant effects were seen on the QTc interval. The goal of this study is to compare the safety and efficacy of maraviroc (UK-427,857) versus efavirenz, when each are combined with two other antiretroviral agents, in patients who are previously naive to antiretroviral therapy. This study will involve approximately 200 centers from around the world to achieve a total randomized subject population of 1071 subjects. Patients will be randomly assigned to one of three groups: maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily), Maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily) or efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily). The study will enroll over approximately an 18 month period (5 months Phase 2b run-in, 13 months Phase 3) with 96 weeks of treatment. This may be extended for an additional 3 years depending on the results at 96 weeks. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 48 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24, 48 and 96. A computerized tomography (CT) scan will also be performed, at selected centers, at study entry and week 96. Patients will be asked to complete a symptom distress questionnaire at study entry, weeks 12, 24, 48 and 96.

Study Overview

• Status: Completed
• Conditions: HIV-1
• Intervention / Treatment: Drug: Maraviroc + Zidovudine/Lamivudine; Drug: Efavirenz + Zidovudine/Lamivudine; Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine

• Study Type: Interventional
• Enrollment (Actual): 916
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Pfizer Investigational Site
  • Ciudad de Buenos, Argentina, C1282AEN
    • Pfizer Investigational Site
  • Ciudad de Buenos Aires, Argentina, C1202ABB
    • Pfizer Investigational Site
  • Ciudad de Buenos Aires, Argentina, C1406FWY
    • Pfizer Investigational Site
  • Provincia de Buenos Aires, Argentina
    • Pfizer Investigational Site
  • Provincia de Santa Fe, Argentina
    • Pfizer Investigational Site
  • Provincia de Buenos Aires
    • El Palomar, Provincia de Buenos Aires, Argentina, 1684
      • Pfizer Investigational Site
  • Provincia de Neuquen
    • Neuquen, Provincia de Neuquen, Argentina, Q8300PMB
      • Pfizer Investigational Site
• Australia
  • New South Wales
    • Burwood, New South Wales, Australia, 2134
      • Pfizer Investigational Site
    • Darlinghurst, New South Wales, Australia, 2010
      • Pfizer Investigational Site
    • Surrey Hills, New South Wales, Australia, 2010
      • Pfizer Investigational Site
    • Wentworthville, New South Wales, Australia, 2145
      • Pfizer Investigational Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Pfizer Investigational Site
    • Miami, Queensland, Australia, 4220
      • Pfizer Investigational Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Pfizer Investigational Site
    • North Fitzroy, Victoria, Australia, 3068
      • Pfizer Investigational Site
    • South Yarra, Victoria, Australia, 3141
      • Pfizer Investigational Site
• Belgium
  • Brussels, Belgium, 1000
    • Pfizer Investigational Site
  • Brussels, Belgium, 1200
    • Pfizer Investigational Site
  • Gent, Belgium, 9000
    • Pfizer Investigational Site
  • Leuven, Belgium, B-3000 Leuven
    • Pfizer Investigational Site
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20210-030
      • Pfizer Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2R0X7
      • Pfizer Investigational Site
    • Edmonton, Alberta, Canada, T6G 2B7
      • Pfizer Investigational Site
    • Edmonton, Alberta, Canada, T6G 2C8
      • Pfizer Investigational Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Pfizer Investigational Site
    • Vancouver, British Columbia, Canada, V6B 1R3
      • Pfizer Investigational Site
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Pfizer Investigational Site
    • Vancouver, British Columbia, Canada, V6Z 2T1
      • Pfizer Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Pfizer Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Pfizer Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Pfizer Investigational Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M5B 1W8
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M5G 2N2
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2W 1T8
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2L 4P9
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2L 4M1
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2L 5B1
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2X 2P4
      • Pfizer Investigational Site
    • Sainte-Foy, Quebec, Canada, G1V 4G2
      • Pfizer Investigational Site
• Italy
  • Antella (FI), Italy, 50011
    • Pfizer Investigational Site
  • Brescia, Italy, 25123
    • Pfizer Investigational Site
  • Milano, Italy, 20127
    • Pfizer Investigational Site
  • Modena, Italy, 41100
    • Pfizer Investigational Site
  • Roma, Italy, 00161
    • Pfizer Investigational Site
  • Roma, Italy, 00185
    • Pfizer Investigational Site
  • Torino, Italy, 10149
    • Pfizer Investigational Site
• Mexico
  • Mexico City
    • Del. Tlalpan C.P., Mexico City, Mexico, 14050
      • Pfizer Investigational Site
  • Mexico D.F.
    • Del. Tlalpan, C.P., Mexico D.F., Mexico, 14000
      • Pfizer Investigational Site
    • Del. Tlalpan, C.P., Mexico D.F., Mexico, 14080
      • Pfizer Investigational Site
    • Delegacion Tlalpan C. P, Mexico D.F., Mexico, 14080
      • Pfizer Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • Pfizer Investigational Site
  • Rotterdam, Netherlands, 3015 GD
    • Pfizer Investigational Site
  • Utrecht, Netherlands, 3584 CX
    • Pfizer Investigational Site
• Poland
  • Bialystok, Poland, 15-540
    • Pfizer Investigational Site
  • Bydgoszcz, Poland, 85-030
    • Pfizer Investigational Site
  • Chorzow, Poland, 41-500
    • Pfizer Investigational Site
  • Gdansk, Poland, 80-214
    • Pfizer Investigational Site
  • Krakow, Poland, 31-531
    • Pfizer Investigational Site
  • Szczecin, Poland, 71-455
    • Pfizer Investigational Site
  • Warszawa, Poland, 01-201
    • Pfizer Investigational Site
• Puerto Rico
  • Ponce, Puerto Rico, 00731
    • Pfizer Investigational Site
  • Rio Piedras, Puerto Rico, 00935
    • Pfizer Investigational Site
  • San Juan, Puerto Rico, 00909
    • Pfizer Investigational Site
  • San Juan, Puerto Rico, 00935
    • Pfizer Investigational Site
• South Africa
  • Bloomfontein, South Africa
    • Pfizer Investigational Site
  • Cape Town, South Africa, 7405
    • Pfizer Investigational Site
  • Cape Town, South Africa, 7550
    • Pfizer Investigational Site
  • Cape Town, South Africa, 7705
    • Pfizer Investigational Site
  • Cape Town, South Africa, 7780
    • Pfizer Investigational Site
  • Johannesburg, South Africa, 2047
    • Pfizer Investigational Site
  • Pretoria, South Africa, 0132
    • Pfizer Investigational Site
  • Pretoria North, South Africa, 0182
    • Pfizer Investigational Site
  • Soweto, Johannesburg, South Africa, 2013
    • Pfizer Investigational Site
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6065
      • Pfizer Investigational Site
  • Free State
    • Bloemfontein, Free State, South Africa, 9300
      • Pfizer Investigational Site
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2092
      • Pfizer Investigational Site
    • Pretoria, Gauteng, South Africa, 0083
      • Pfizer Investigational Site
  • KwaZulu Natal
    • Dundee, KwaZulu Natal, South Africa, 3000
      • Pfizer Investigational Site
• Switzerland
  • Basel, Switzerland, 4031
    • Pfizer Investigational Site
  • Bern, Switzerland, 3010
    • Pfizer Investigational Site
  • Genève, Switzerland, 1211
    • Pfizer Investigational Site
  • Lugano, Switzerland, 6900
    • Pfizer Investigational Site
  • St. Gallen, Switzerland, 9007
    • Pfizer Investigational Site
  • Zürich, Switzerland, 8038
    • Pfizer Investigational Site
  • Zürich, Switzerland, 8091
    • Pfizer Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Pfizer Investigational Site
  • Brighton, United Kingdom, BN2 1ES
    • Pfizer Investigational Site
  • Edinburgh, United Kingdom, EH4 2XU
    • Pfizer Investigational Site
  • London, United Kingdom, SE5 9RS
    • Pfizer Investigational Site
  • London, United Kingdom, NW3 2QG
    • Pfizer Investigational Site
  • London, United Kingdom, SW10 9NH
    • Pfizer Investigational Site
  • London, United Kingdom, W2 1NY
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M8 5RB
    • Pfizer Investigational Site
  • Loth
    • Edinburgh, Loth, United Kingdom, ED4 2XU
      • Pfizer Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35294-2050
      • Pfizer Investigational Site
  • California
    • Beverly Hills, California, United States, 90211
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90048
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90022
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90069
      • Pfizer Investigational Site
    • Newport Beach, California, United States, 92663
      • Pfizer Investigational Site
    • Oakland, California, United States, 94602
      • Pfizer Investigational Site
    • Sacramento, California, United States, 95825
      • Pfizer Investigational Site
    • San Francisco, California, United States, 94115
      • Pfizer Investigational Site
    • San Francisco, California, United States, 94115-3029
      • Pfizer Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Pfizer Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33136
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33133
      • Pfizer Investigational Site
    • Miami Beach, Florida, United States, 33139
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32803
      • Pfizer Investigational Site
    • Sarasota, Florida, United States, 34243
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33614
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Pfizer Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02215
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02118-2393
      • Pfizer Investigational Site
    • Springfield, Massachusetts, United States, 01107
      • Pfizer Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • Pfizer Investigational Site
  • New York
    • Albany, New York, United States, 12208
      • Pfizer Investigational Site
    • Brooklyn, New York, United States, 11203
      • Pfizer Investigational Site
    • Flushing, New York, United States, 11355
      • Pfizer Investigational Site
    • Manhasset, New York, United States, 11030
      • Pfizer Investigational Site
    • New York, New York, United States, 10016
      • Pfizer Investigational Site
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Pfizer Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0405
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73104-5068
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Pfizer Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29206
      • Pfizer Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75208
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77006
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77098
      • Pfizer Investigational Site
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Pfizer Investigational Site
  • Washington
    • Puyallup, Washington, United States, 98372
      • Pfizer Investigational Site
    • Tacoma, Washington, United States, 98405
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women at least 16 years of age (or minimum age as determined by local regulatory authorities)
• HIV-1 RNA viral load of greater than or equal to 2, 000 copies/mL
• A negative urine pregnancy test at the baseline visit for Women of Child Bearing Potential (WOCBP)
• Effective barrier contraception for WOCBP and males

Exclusion Criteria:

• Suspected or documented active, untreated HIV-1 related opportunistic infection (OI) or other condition requiring acute therapy
• Treatment for an active opportunistic infection, or unexplained temperature >38.5 degrees Celsius for 7 consecutive days
• Prior treatment with efavirenz, zidovudine or lamivudine or with any other antiretroviral therapy for more than 14 days at any time
• Active alcohol or substance abuse sufficient, in the Investigator's judgment, to prevent adherence to study medication and/or follow up
• Lactating women, or planned pregnancy during the trial period
• Suspected primary (acute) HIV-1 infection
• Previous therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 30 days prior to randomization or the expected need for such therapy during the study period
• Documented or suspected acute hepatitis or pancreatitis within 30 days prior to randomization
• Significantly elevated liver enzymes or cirrhosis
• Significant neutropenia, anemia or thrombocytopenia
• Malabsorption or an inability to tolerate oral medications
• Symptomatic postural hypotension or severe cardiovascular or cerebrovascular disease
• Certain medications
• Genotypic or phenotypic resistance to efavirenz, zidovudine or lamivudine
• X4- or dual/mixed-tropic virus or repeated assay failure
• Any other clinical condition that, in the Investigator's judgement, would potentially compromise study compliance or the ability to evaluate safety/efficacy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Maraviroc + Zidovudine/Lamivudine; maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)
Active Comparator: 3	Drug: Efavirenz + Zidovudine/Lamivudine; efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily)
Experimental: 2; Following a review of the interim analysis data, the DSMB recommended to terminate the UK-427,857 300 mg QD arm based on pre-specified protocol non-inferiority criteria not being met for the QD arm versus efavirenz	Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine; maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Viral Load of Less Than 400 Copies/Milliliter [Copies/mL] and Less Than 50 Copies/mL of Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) at Week 48 for Full Analysis Set (FAS) Population		Week 48
Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 48 for Per Protocol (PP) Population	Percentage of participants with viral load of less than 400 copies/mL and less than 50 copies/mL of HIV-1 RNA were not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 Analyzed Using Logistic Regression		Week 48
Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 Analyzed Using Logistic Regression		Week 96
Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96	Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.	Baseline, Week 48, Week 96
Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels	TAD from baseline was calculated as area under the curve (AUC) of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose. Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.	Baseline up to Week 48 and Week 96
Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96	Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.	Baseline, Week 48, Week 96
Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 48 and 96	Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose. Change from baseline in lymphocyte CD8 count at Week 48 and 96 was not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.	Baseline, Week 48, Week 96
Time to Virologic Failure	Time to virologic failure based on observed HIV-1 RNA levels and failure events (death;permanent discontinuation of drug;lost to follow-up [LTFU];new anti-retroviral drug added [except background drug change to drug of same class];or on open label for early non-response or rebound). Failure:at Time 0 if level not <400 copies/mL(2 consecutive visits) before events or last available visit;at time of earliest event if level <400 copies/mL(2 consecutive visits);failure if level >=400 copies/mL(2 consecutive visits) or 1 visit >=400 copies/mL followed by permanent discontinuation of drug or LTFU.	Week 48, Week 96
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48	Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 48 visit. Treatment failure: discontinuation due to insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as last on treatment assessment.	Baseline, time of failure through Week 48
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 96	Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 96 visit. Treatment failure defined as insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as BLQ. The assessment for time of treatment failure was defined as last on treatment assessment.	Baseline, time of failure through Week 96
Number of Participants With Phenotypic Resistance at Time of Treatment Failure Through Week 48 and 96	Phenotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) assessed at screening by Monogram Bioscience PhenoSense genotype (MBPSGT) assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Phenotypic resistance to maraviroc was assumed in maraviroc treatment failures with X4-using virus and in R5 maraviroc treatment failures using Monogram Bioscience PhenoSense Entry Assay. Phenotypic resistance to zidovudine, lamivudine, efavirenz and maraviroc at time of failure was summarized.	Screening, time of failure through Week 48, Week 96
Number of Participants With NRTI Associated Mutations at Time of Treatment Failure Through Week 48 and 96	Genotypic resistance to NRTIs was assessed by identification of relevant mutations at screening using MBPSGT assay and repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure through week 48 and week 96. Following mutations associated with NRTIs were summarized at time of failure: Any zidovudine/lamivudine (Zid/Lam), Any thymidine analogue-associated mutation (TAM), methionine (M) to valine/isoleucine (V/I) substitution at residue (r) 184 (M184V/I), lysine (K) to arginine (R) substitution at residue 65 (K65R) and any other NRTI mutations.	Screening, time of failure through Week 48, Week 96
Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96	Genotypic resistance: mutations at screening by MBPSGT assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Efavirenz mutation:lysine to aspargine at r103(K103N);tyrosine to cysteine/isoleucine at r181(Y181C/I);tyrosine to cysteine/leucine/histidine at r188(Y188C/L/H);glycine to alanine/serine at r190(G190A/S);valine to alanine to r106(V106A);leucine to isoleucine at r100(L100I);alanine to glycine at r98(A98G);lysine to glutamic acid at r101(K101E);valine to isoleucine at r108(V108I);proline to histidine at r225(P225H);methionine to leucine at r230(M230L).	Screening, time of failure through Week 48, Week 96
Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening	Association between baseline resistance and virological response was assessed as percentage of participants with HIV-1RNA levels less than 50 copies/mL by OSS at screening. OSS categorized as 0, 1, 2, >3 (maximum value of 6) and calculated as the sum of the net assessment of in-vitro phenotypic and genotypic susceptibility using a binary scoring system (0= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.	Baseline, Week 48, Week 96

Other Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 96	Week 96

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: Pfizer

Publications and helpful links

General Publications

• Vourvahis M, McFadyen L, Nepal S, Valluri SR, Fang A, Fate GD, Wood LS, Marshall JC, Chan PLS, Nedderman A, Haynes J, Savage ME, Clark A, Smith KY, Heera J. No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV-1-Infected Subjects. J Clin Pharmacol. 2019 Jan;59(1):139-152. doi: 10.1002/jcph.1306. Epub 2018 Sep 7.
• MacInnes A, Lazzarin A, Di Perri G, Sierra-Madero JG, Aberg J, Heera J, Rajicic N, Goodrich J, Mayer H, Valdez H. Maraviroc can improve lipid profiles in dyslipidemic patients with HIV: results from the MERIT trial. HIV Clin Trials. 2011 Jan-Feb;12(1):24-36. doi: 10.1310/hct1201-24.
• Funderburg N, Kalinowska M, Eason J, Goodrich J, Heera J, Mayer H, Rajicic N, Valdez H, Lederman MM. Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patients. PLoS One. 2010 Oct 6;5(10):e13188. doi: 10.1371/journal.pone.0013188.
• Cooper DA, Heera J, Goodrich J, Tawadrous M, Saag M, Dejesus E, Clumeck N, Walmsley S, Ting N, Coakley E, Reeves JD, Reyes-Teran G, Westby M, Van Der Ryst E, Ive P, Mohapi L, Mingrone H, Horban A, Hackman F, Sullivan J, Mayer H. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis. 2010 Mar 15;201(6):803-13. doi: 10.1086/650697.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): April 1, 2007
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: December 6, 2004
• First Submitted That Met QC Criteria: December 6, 2004
• First Posted (Estimate): December 7, 2004

Study Record Updates

• Last Update Posted (Estimate): October 9, 2013
• Last Update Submitted That Met QC Criteria: August 7, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: HIV; Aids
• 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; Antimetabolites; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Cytochrome P-450 CYP2C19 Inhibitors; Lamivudine; Zidovudine; Maraviroc; Efavirenz
• Other Study ID Numbers: A4001026