A MULTICENTER, RANDOMIZED, DOUBLE BLIND, COMPARATIVE TRIAL OF MARAVIROC + DARUNAVIR/RITONAVIR VERSUS EMTRICITABINE/TENOFOVIR + DARUNAVIR/RITONAVIR FOR THE TREATMENT OF ANTIRETROVIRAL NAÏVE HIV INFECTED PATIENTS WITH CCR5 TROPIC HIV 1

INTERVENTION:

Trade Name: Celsentri Product Name: maraviroc Product Code: UK‐427,857 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

Maraviroc CAS Number: 376348‐65‐1 Current Sponsor code: UK‐427,857 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Trade Name: Truvada Product Name: emtricitabine & tenofovir Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

EMTRICITABINE CAS Number: 143491‐57‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed

INN:

TENOFOVIR DISOPROXYL FUMARATE CAS Number: 147127‐20‐6 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 245‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Trade Name: Prezista Product Name: Darunavir Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

DARUNAVIR CAS Number: 206361‐99‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 800‐ Trade Name: Norvir Product Name: Ritonavir Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

RITONAVIR CAS Number: 155213‐67‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐

CONDITION:

HIV infection ; MedDRA version: 14.0 Level: LLT Classification code 10068341 Term: HIV‐1 infection System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02]

PRIMARY OUTCOME:

Main Objective: To assess whether maraviroc (SelzentryTM, Celsentri®) administered once daily (QD) is non inferior to a reference regimen of emtricitabine/tenofovir administered QD each in combination with darunavir/ritonavir in the treatment of antiretroviral naïve HIV 1 infected subjects as measured by the proportion of subjects with HIV 1 RNA below the limits of assay detection (<50 copies of HIV 1 RNA per milliliter of plasma) at Week 48. Primary end point(s): The proportion of subjects with plasma HIV 1 RNA <50 copies/mL at Week 48. Secondary Objective: 1. To assess the safety and tolerability of maraviroc when administered in combination with darunavir/ritonavir.; 2. To assess the utility of genotype testing or the enhanced Trofile assay (ESTA) for tropism testing in predicting virologic outcomes of a maraviroc containing regimen.; 3. To compare the proportion of subjects with HIV 1 RNA below the limits of assay detection at Week 96 for maraviroc versus emtricitabine/tenofovir.; 4. To compare the differences in the magnitude of changes in CD4+ and CD8+ cell counts and CD4+/CD8+ ratio from baseline through Weeks 48 and 96 for maraviroc versus emtricitabine/tenofovir.; 5. To examine tropism change and the evolution of viral resistance in virologic failure subjects. ; 6. To compare the effects on peripheral fat distribution and trunk to limb fat ratio of maraviroc versus emtricitabine/tenofovir.; 7. To compare the effects on bone mineral density of maraviroc versus emtricitabine/tenofovir; Timepoint(s) of evaluation of this end point: Week 48 ; 3. Virologic Response: ; Proportion of subjects with plasma HIV RNA <50 copies/mL at Week 96. ; 4. Immunological Response at Week 48 and Week 96: ; a. Changes in CD4+ T lymphocyte (CD4) cell counts and percent change from Baseline; ; b. Changes in CD8+ T lymphocyte (CD8) cell counts and percent change from Baseline; ; c. Changes in CD4+/CD8+ ratio and changes from Baseline. ; 5. Evolution of viral resistance and tropism change between Screening or Baseline and the time of confirmation of virologic failure or the last on treatment time point: ; a. HIV 1 tropism (Genotype test)

SECONDARY OUTCOME:

Secondary end point(s): 1. Safety: Frequency, severity and relationship of adverse events to test drug; serious adverse events; discontinuations due to adverse events; and frequency and severity of abnormal laboratory values. ; 2. The relationship between the proportion of subjects with plasma HIV 1 RNA <50 copies/mL at the Week 48 and Week 96 visits and the screening tropism test (Genotype test or ESTA) in the maraviroc‐containing regimen.. ; b. For virologic failure with R5 virus, viral resistance to maraviroc (maraviroc treated subjects only). ; c. Viral resistance (Genotype and Phenotype) to nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) and non nucleoside reverse transcriptase inhibitors (NNRTI) [reverse transcriptase inhibitors, RTI] and protease inhibitors (PI). ; 6. Changes in peripheral fat distribution and trunk to limb fat ratio (using DEXA scan) from Baseline and at Weeks 48 and 96 (approximately 109 subjects per treatment arm). ; 7. Changes in bone mineral density (using DEXA scan and serum markers) from Baseline and at Weeks 48 and 96 (approximately 109 subjects per treatment arm). ; Timepoint(s) of evaluation of this end point: Weeks 48 and 96

INCLUSION CRITERIA:

1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study 2. At least 18 years of age at the Screening Visit. 3. Plasma HIV 1 RNA equal to or more than 1,000 copies/mL measured at the Screening Visit. 4. CD4 count equal to or more than 100 cells/mm3 at Screening. 5. Have only R5 HIV 1 at Screening as verified by a randomized tropism assay. 6. A negative urine pregnancy test at Screening and at the Baseline Visit, prior to receiving the first dose of study medication, for Women of Child Bearing Potential (WOCBP).

NOTE:

WOCBP include any female who has experienced menarche and who has not undergone hysterectomy, bilateral oophorectomy or tubal ligation or any other successful surgical sterilization or is not post menopausal (age >45 years, amenorrheic for >2 years, and serum FSH