MARCH

INTERVENTION: Trade Name: Celsentri Product Name: Celsentri Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: maraviroc CAS Number: 192725170 Current Sponsor code: H‐C‐368 Other descriptive name: CELSENTRI (maraviroc) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐600 CONDITION: Chronic HIV‐1 infection ; MedDRA version: 14.0 Level: LLT Classification code 10008919 Term: Chronic HIV infection System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: The primary objective of this study is to compare the virological efficacy of switching HIV‐1 infected participants virologically suppressed on a combination of a nucleoside/nucleotide reverse transcriptase inhibitor backbone (nRTI) with a ritonavir‐boosted protease inhibitor (PI/r) to remain on their current combination (arm 1 or control) or switch to a PI/r with maraviroc (arm 2) or nRTI plus maraviroc (arm 3) for 90 weeks of follow‐up. The primary comparison of interest is the proportion of patients with HIV RNA <200 copies/mL 48 weeks after randomisation in the maraviroc arms vs. control arm. Primary end point(s): The comparison of the switch arms to control arm of proportions of participants with HIV RNA <200 copies/mL 48 weeks after randomisation in the intention‐to‐treat (ITT) population. Secondary Objective: A number of secondary outcomes will be assessed which are of relevance and interest in the assessment of the performance of the three study treatment regimens. These will include (but will not necessarily be limited to) virological, immunological, safety, clinical, metabolic, body composition changes, medication adherence and quality of life. Timepoint(s) of evaluation of this end point: Week 48 SECONDARY OUTCOME: Secondary end point(s): A number of secondary endpoints will be examined at or through to week 48 in this protocol. These will include, but not be limited to the following: ; Virologic endpoints ; • Proportion of participants with plasma HIV RNA <50 copies/mL ; • Time to virological failure (defined as plasma HIV RNA =200 copies/mL on randomised therapy, on two occasions at least seven days apart) ; • Time to loss of virological response, as defined by virological failure, permanent discontinuation of randomised treatment, new AIDS‐defining illness, death or withdrawal from the study ; • Changes from baseline in log plasma HIV RNA copies/mL ; • Frequency of plasma HIV RNA blips (defined as a plasma viral load result >200 copies/mL on randomised therapy following a previous result <200 copies/mL, with a follow‐up result <200 copies/mL at least seven days after the >200 copies/mL reading, in the absence of a change of any component of the ART regimen). ; Immunologic and biomarker endpoints ; • Changes from baseline in absolute and percentage CD4+ T cells ; • Changes from baseline in selected soluble markers of immune activation/coagulation. ; Clinical endpoints ; • Rate of opportunistic disease (AIDS) or death ; • Rates of Serious Non‐AIDS‐defining illness and Non‐AIDS‐related mortality. ; Metabolic and body composition endpoints ; • Changes from baseline in fasting lipids (TC, LDL‐c, HDL‐c and TG) ; • Changes in absolute CVD risk assessment using the Framingham risk equation ; • Changes from baseline in fasting glucose and insulin ; • Rates of initiation or changes in existing lipid‐lowering therapies ; • Changes from baseline in anthropometric changes derived from Dual‐energy X‐ray absorptiometry (DXA) scanning of peripheral and central adipose tissue ; • Changes from baseline in bone mineral density as measured by DXA ; • Changes in 10‐year fracture risk using the FRAX® algorithm ; • Changes from baseline in markers of bone turnover. ; Safety ; • Changes from baseline in selected serum biochemical parameters, including changes in estimated glomerular filtration rate ; • Proportions experiencing and types of SAEs ; • Proportions experiencing, types and severity of AEs. ; Adherence ; • Self‐reported adherence to randomised study medications. ; Quality of Life ; • Change from baseline health status scores as measured by the SF‐12 health status. ; Resistance endpoints ; • Patterns of genotypic resistance at virological failure. ; Timepoint(s) of evaluation of this end point: Week 48 INCLUSION CRITERIA: 1. HIV‐1 positive by licensed diagnostic test 2. Aged 18 years or older 3. HIV‐1 RNA <200 copies/mL plasma for at least 24 weeks 4. Stable (>24 weeks) ART including two N(t)RTIs and a PI/r 5. No evidence of any primary HIV genotypic mutations in HIV reverse transcriptase or protease for all patients with available resistance testing results conducted prior to cART and/or during viral rebound/failure 6. Able to provide written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 544 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16