Nevirapine or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir in Human Immunodeficiency Virus (HIV)-1-infected Treatment Naive Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: nevirapine bid; nevirapine qd; atazanavir
Intervention description: nevirapine twice daily; nevirapine once daily; atazanavir once daily
Intervention MeSH terms: Atazanavir Sulfate; Nevirapine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 576.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary purpose of this study is to compare the efficacy and safety of two different
      nevirapine (Viramune) dosing regimens (once daily (QD) and twice daily (BID) application) and
      of atazanavir/ritonavir (Reyataz/Norvir), all on an emtricitabine/tenofovir disoproxil
      fumarate (DF) (Truvada) background. Patients will receive either nevirapine (NVP) 200 mg
      twice daily, or NVP 400 mg once daily , or ritonavir-boosted atazanavir (ATZ/r), all in
      combination with emtricitabine (FTC) and tenofovir DF (TDF).

      All patients receiving NVP will start at 200 mg once daily for 2 weeks, because it has been
      demonstrated that this lead-in dosing regimen reduces the frequency of NVP-induced rash. At
      Visit 3 (Week 2), patients increase the NVP dose to either 200 mg twice daily or to 400 mg
      once daily. Patients receiving ATZ/r will be treated with ATZ 300 mg once daily, boosted by
      100 mg ritonavir (RTV) once daily. Background antiretroviral therapy for all patients
      consists of one tablet of Truvada. Treatment duration is 48 weeks (primary endpoint) with an
      extension to 144 weeks. Patients may also participate in the metabolic sub-study, comparing
      NVP and ATZ/r for signs and symptoms of lipodystrophy and serum lipid/glycaemic
      abnormalities.
    

Eligibility criteria:

        Inclusion criteria:

        Inclusion Criteria:

          1. Signed informed consent in accordance with Good Clinical Practice (GCP) and local
             regulatory requirements prior to trial participation

          2. HIV-1-infected males or females >= 18 years of age with positive serology confirmed by
             Western blot

          3. No previous antiretroviral treatment (of more than 7 days)

          4. Males with CD4+ counts of < 400 cells/mm3 and females with CD4+ counts of < 250
             cells/mm3

          5. NVP- and ATZ/r susceptibility based on HIV-1 genotypic resistance report

          6. Adequate renal function defined as a calculated creatinine clearance (CLCr) >= 50
             ml/min according to the Cockcroft-Gault formula

          7. Karnofsky score >= 70

          8. Acceptable medical history, as assessed by the investigator

        Exclusion criteria:

        Exclusion Criteria:

          1. Active drug abuse or chronic alcoholism at the investigator's discretion

          2. Hepatic cirrhosis stage Child-Pugh B or C

          3. Female patients of child-bearing potential who:

               -  have a positive serum pregnancy test at screening or during the study,

               -  are breast feeding,

               -  are planning to become pregnant,

               -  are not willing to use a barrier method of contraception, or are not willing to
                  use methods of contraception other than ethinyl estradiol containing oral
                  contraceptives

          4. Laboratory parameters Division of Acquired Immunodeficiency Syndrome (DAIDS) > grade 2
             (triglycerides > DAIDS grade 3; total cholesterol no restrictions)

          5. Active hepatitis B or C disease, defined as HBsAg-positive or Hepatitis C-Virus-Ribo
             Nucleic Acid (HCV-RNA)- positive with Aspartate Transaminase/Alanine Transaminase
             (AST/ALT) > 2.5x Upper Limit of Normal (ULN) (DAIDS grade 1)

          6. Hypersensitivity to any ingredients of the test products

          7. Have therapy with nephrotoxic drugs (e.g., aminoglycosides, amphotericin B,
             vancomycin, cidofovir, foscarnet, cisplatin, pentamidine, tacrolimus, cyclosporine) or
             potential competitors of renal excretion (e.g., cidofovir, acyclovir, valacyclovir,
             ganciclovir, valganciclovir, probenecid, high-dose non-steroidal anti-inflammatory
             drugs (i.e., ibuprofen)) within 3 months prior to study screening or are expected to
             receive these during the study

          8. Patients who are receiving other concomitant treatments which are not permitted

          9. Use of other investigational medications within 30 days before study entry or during
             the trial

         10. Use of immunomodulatory drugs within 30 days before study entry or during the trial
             (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2, chronic treatment with
             prednisone)

         11. Patients with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's
             Sarcoma (KS), and/or any lymphoma

         12. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment
             for at least 12 weeks at screening visit

         13. Patients who are receiving systemic treatment for malignant disease