TMC125-TiDP2-C238: An Exploratory Pharmacokinetics, Safety and Anti-HIV Activity Study of Etravirine (ETR) When Given With Boosted Atazanavir (ATV/Rtv) at Two Different Doses and 1 Nucleoside Reverse Transcriptase Inhibitor (NRTI) in Treatment Experienced HIV Patients
Condition: HIV Infections; Acquired Immunodeficiency Syndrome
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
Intervention: Atazanavir (ATV) 300 mg; Atazanavir (ATV) 400 mg; Ritonavir (rtv) 100 mg; Nucleo(side)/(tide) reverse transcriptase inhibitors (NRTIs); Etravirine (ETR) 200 mg; Tenofovir disoproxil fumarate (TDF) 300 mg
Intervention description: Atazanavir (ATV) 300 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take ATV 300 mg by mouth following a meal each morning on Substudy Days -1 to 7.; Atazanavir (ATV) 400 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take ATV 400 mg by mouth following a meal each morning on Substudy Days -1 to 7.; Ritonavir (rtv) 100 mg taken by mouth following a meal each morning for 2 weeks during the Pre-Treatment Period and for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take rtv 100 mg by mouth following a meal each morning on Substudy Days -1 to 7.; 2 investigator-selected NRTIs taken as specified in the individual product labels for 2 weeks during the Pre-Treatment Period followed by 1 investigator-selected NRTI (of the 2 NRTIs in the Pre-Treatment Phase) taken as specified in the individual product label for 48 weeks during the Treatment Period. If participating in the optional substudy, participants will take 1 investigator-selected NRTI (of the 2 NRTIs in the Pre-Treatment Phase) mg taken as specified in the individual product label during the Substudy.; Etravirine (ETR) 200 mg taken twice daily as two 100-mg tablets following a meal (morning and evening) for at least the first two weeks of the 48-week Treatment Period. If participating in the optional substudy, participants will take ETR 200 mg twice daily as two 100-mg tablets following a meal each morning and evening on Substudy Days -1 to 7.; Tenofovir disoproxil fumarate (TDF) 300 mg taken by mouth following a meal each morning on Substudy Days 1 to 7.
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate; Tenofovir; Etravirine; Reverse Transcriptase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV Infections; Acquired Immunodeficiency Syndrome; TMC125-TiDP2-C238; TMC125-C238; Etravirine; Intelence; HIV; HIV-1; Pharmacokinetics

Summary:

      The purpose of this study is to determine the pharmacokinetics (how the body absorbs,
      distributes, metabolizes and eliminates a drug) (PK) of ETR when given with ATV/rtv and 1
      NRTI in treatment experienced HIV-1 infected patients. In addition, safety, tolerability and
      anti-HIV effect of this regimen will also be studied. A total of 46 patients will be
      enrolled.
    

Eligibility criteria:

        Inclusion Criteria:

        - Documented HIV-1 infection

          -  Failing on a stable ART (anti retroviral therapy) with HIV-1 plasma viral load above
             500 HIV-1 RNA copies/ml

          -  Presence of at least 1 documented NNRTI mutation

          -  Demonstrated sensitivity to ATV, ETR and at least one of the selected NRTIs based on
             the resistance test at screening

          -  General medical condition, in the investigator's opinion, does not interfere with the
             assessments and completion of the trial

          -  Substudy: patients who have been treated in C238 for more than 24 weeks and are
             currently suppressed (defined as patients with at least 2 most recent and consecutive
             viral loads less than 50 cp/mL) will be considered eligible for the substudy

        Exclusion Criteria:

          -  Primary HIV-1 infection

          -  Previously documented HIV-2 infection

          -  Previously failed 2 or more HIV PI-containing regimens

          -  Previous diagnosis of hereditary hyperbilirubinemia (eg. Gilbert's syndrome,
             Crigler-Najjar syndrome).

        Grade 3 or 4 toxicities (according to DAIDS grading)

          -  Acute and chronic viral hepatitis

          -  Receipt of an investigational drug or investigational vaccine within 30 days prior to
             the trial drug administration

          -  Pregnant or breastfeeding female