A Phase III, randomized, double-blind, placebo-controlled, multicenter, parallel group study to compare the efficacy and safety of GW873140 400mg BID in combination with a ritonavir-containing optimized background therapy (OBT) regimen versus placebo plus OBT over 48 weeks in HIV-1 infected, treatment-experienced subjects with drug-resistant CCR5/CXCR4-tropic virus

INTERVENTION: Product Name: GW873140 Product Code: GW873140 Pharmaceutical Form: Film‐coated tablet CAS Number: 461023‐63‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Treatment of HIV‐1 infection PRIMARY OUTCOME: Main Objective: • To demonstrate the superiority of GW873140 400mg BID plus Optimised Background Therapy (OBT) compared to placebo plus OBT, as measured by the difference in plasma HIV‐1 RNA average area under the curve minus baseline (AAUCMB) between the two treatment arms at 24 and 48 weeks. Primary end point(s): •Antiviral activity of GW873140 400mg BID plus OBT versus placebo plus OBT, following 24 and 48 weeks of treatment as measured by plasma HIV‐1 RNA AAUCMB. Secondary Objective: •Assess antiviral activity of GW873140 400mg BID plus OBT compared to PBO plus OBT as measured by:; •Proportion with sustained plasma HIV‐1 RNA <400 and <50copies/mL,.; •Estimated TLOVR based on plasma HIV‐1 RNA <400 and <50copies/mL ; •Proportion of subjects with a ?1.0 log10 copies/mL decrease in plasma HIV‐1 RNA from baseline ; •Evaluate safety and tolerability, immunologic markers, HIV disease progression, of antiretroviral resistance to GW873140 and other on‐study drugs ; •Explore relationships between baseline HIV‐1 resistance to on‐study drugs and antiviral response.; •Evaluate qualitative changes in viral tropism ; •Evaluate plasma PK of GW873140 400mg BID when used in combination with OBT. ; •Explore how bothersome certain symptoms are and how symptoms impact on health related QofL.; •Evaluate adherence.; ; INCLUSION CRITERIA: 1.HIV‐1 infected subjects aged 18 years or older. Females must fall into one of the following categories: •Non‐childbearing potential: defined as women who are surgically sterile or post‐menopausal, •Childbearing potential has a negative pregnancy test result within 35 days prior to administration of investigational product (Day 1) and agrees to use a proven double barrier method of contraception. 2.Screening plasma HIV‐1 RNA =5000copies/mL There are no CD4 cell count entry restrictions, however investigators must exercise clinical discretion 3.Total prior antiretroviral experience of at least 3 months and documented genotypic or phenotypic resistance to at least one compound in each of the following classes of antiretrovirals: NRTIs (includes NtRTI TDF), NNRTIs, and PIs. 4.R5/X4‐tropic virus according to viral tropism assessment at screening 5.Current unchanged “pre‐study” ART regimen for at least four weeks prior to screening; this pr