A randomized, controlled, open-label trial to compare the efficacy, safety and tolerability of TMC114/RTV versus LPV/RTV in treatment-experienced HIV-1 infected subjects

INTERVENTION: Product Name: TMC114 ethanolate Product Code: TMC114 Pharmaceutical Form: Tablet CAS Number: 206361‐99‐1 Current Sponsor code: TMC114 Other descriptive name: TMC114 ethanolate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Trade Name: Norvir Product Name: Norvir Pharmaceutical Form: Capsule* INN or Proposed INN: ritonavir CAS Number: 155213‐67‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Kaletra Product Name: Kaletra Pharmaceutical Form: Capsule, soft INN or Proposed INN: lopinavir CAS Number: 192725‐17‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 133.3‐ INN or Proposed INN: ritonavir CAS Number: 155213‐67‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 33.3‐ CONDITION: HIV‐1 infection PRIMARY OUTCOME: Main Objective: The primary objective is to demonstrate non‐inferiority in virologic response, defined as a confirmed plasma viral load of less than 400 copies/mL, with TMC114/RTV 600/100 mg b.i.d. versus LPV/RTV 400/100 mg b.i.d. at 48 weeks, when administered in combination with an individually optimized background regimen (OBR). Primary end point(s): demonstration of non‐inferiority in efficacy of TMC114/RTV versus lopinavir/ritonavir Secondary Objective: The secondary objectives are:; ‐ to evaluate safety and tolerability over 96 weeks;; ‐ to evaluate the durability of efficacy over 96 weeks;; ‐ to evaluate the change in viral load from baseline;; ‐ to evaluate the percentage of subjects with undetectable viral load defined as viral load < 50 copies/mL);; ‐ to compare the immunologic response;; ‐ to compare the quality of life. INCLUSION CRITERIA: 1. Male or female subjects, aged 18 years or older. 2. Subjects with documented HIV‐1 infection. 3. Treatment with HAART regimen for at least 12 weeks. Note: Structured treatment interruption of a minimum of 4 weeks is allowed. Note: HAART (Highly Active Antiretroviral Therapy) is defined as potent anti‐HIV treatment usually including a combination of three or more drugs with activity against HIV whose purpose is to reduce viral load to undetectable. This regimen usually includes treatment with at least 2 NRTIs in combination with at least 1 additional ARV from the NNRTI and/or PI class. 4. Prescreening and screening plasma HIV‐1 RNA > 1000 copies/mL (assayed by RNA PCR standard specimen procedure). Note: If no documented prescreening viral load is available (taken at least 12 weeks after starting the current HAART regimen), a prescreening visit should be scheduled. 5. Subjects have voluntarily signed the informed consent form. 6. Sub