Nevirapine or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir in Human Immunodeficiency Virus (HIV)-1-infected Treatment Naive Adults

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: HIV Infections

Treatments: Drug: atazanavir; Drug: nevirapine qd; Drug: nevirapine bid

Study type: Interventional

Funder types: Industry

Identifiers

NCT00389207

1100.1470

2005-004330-40 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 576 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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576 participants in 3 patient groups

NVP bid

Active Comparator group

Description:

nevirapine (NVP) 200 mg BID in combination with emtricitabine (FTC) and tenofovir DF (TDF)

Treatment:

Drug: nevirapine bid

NVP qd

Experimental group

Description:

nevirapine (NVP) 400 mg QD in combination with emtricitabine (FTC) and tenofovir DF (TDF)

Treatment:

Drug: nevirapine qd

ATZ/r

Active Comparator group

Description:

ritonavir-boosted atazanavir in combination with emtricitabine (FTC) and tenofovir DF (TDF)

Treatment:

Drug: atazanavir