Nevirapine or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir in Human Immunodeficiency Virus (HIV)-1-infected Treatment Naive Adults
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00389207
- Lead Sponsor
- Boehringer Ingelheim
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 576
- Signed informed consent in accordance with Good Clinical Practice (GCP) and local regulatory requirements prior to trial participation
- HIV-1-infected males or females >= 18 years of age with positive serology confirmed by Western blot
- No previous antiretroviral treatment (of more than 7 days)
- Males with CD4+ counts of < 400 cells/mm3 and females with CD4+ counts of < 250 cells/mm3
- NVP- and ATZ/r susceptibility based on HIV-1 genotypic resistance report
- Adequate renal function defined as a calculated creatinine clearance (CLCr) >= 50 ml/min according to the Cockcroft-Gault formula
- Karnofsky score >= 70
- Acceptable medical history, as assessed by the investigator
Exclusion criteria:
-
Active drug abuse or chronic alcoholism at the investigator's discretion
-
Hepatic cirrhosis stage Child-Pugh B or C
-
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
-
Laboratory parameters Division of Acquired Immunodeficiency Syndrome (DAIDS) > grade 2 (triglycerides > DAIDS grade 3; total cholesterol no restrictions)
-
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)
-
Hypersensitivity to any ingredients of the test products
-
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
-
Patients who are receiving other concomitant treatments which are not permitted
-
Use of other investigational medications within 30 days before study entry or during the trial
-
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)
-
Patients with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma
-
Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit
-
Patients who are receiving systemic treatment for malignant disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NVP bid nevirapine bid nevirapine (NVP) 200 mg BID in combination with emtricitabine (FTC) and tenofovir DF (TDF) NVP qd nevirapine qd nevirapine (NVP) 400 mg QD in combination with emtricitabine (FTC) and tenofovir DF (TDF) ATZ/r atazanavir ritonavir-boosted atazanavir in combination with emtricitabine (FTC) and tenofovir DF (TDF)
- Primary Outcome Measures
Name Time Method Treatment Response at Week 48 From baseline to Week 48 Treatment response is defined as a viral load (VL) \<50 copies/mL measured at two consecutive visits prior to Week 48 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 48.
- Secondary Outcome Measures
Name Time Method Treatment Response at Week 48 (TLOVR Algorithm) From baseline to Week 48 Treatment response is defined as a VL \<50 copies/mL measured at two consecutive visits up to Week 48 and without subsequent rebound or change of ARV therapy up to Week 48, based on time to loss of virologic response (TLOVR) algorithm, as a sensitivity analysis for the primary analysis.
Time to Loss of Virologic Response (Rebound) Baseline to week 144 Time to loss of virologic response (TLOVR) was defined as the time from start of treatment to the first measurement showing VL ≥ 50 copies/mL in the first virologic rebound, after having a confirmed virological response.
Time to Treatment Failure baseline to week 144 Treatment failure is defined as the occurrence of the first of at least one of the following events: early discontinuation of trial drug, change in ARV therapy, failure to achieve an HIV RNA count \< 50 copies/mL up to Visit 10 (week 48) or loss of virologic response
Change in the Calculated Glomerular Filtration Rate (GFR) at Week 48, 96 and 144 From baseline to Week 48, 96, 144 Calculations based on the MDRD algorithm.
Proportion of Patients With >= DAIDS Grade 2 Laboratory Abnormalities week 148 Proportion of Patients Reporting Rash of Any Severity week 148 Proportion of Patients reporting rash of any severity
Proportion of Patients Reporting Hepatic Events of Any Severity week 148 Proportion of Patients reporting hepatic events of any severity
Proportion of Patients Reporting CNS (Central Nervous System) Side Effects of Any Severity week 148 Proportion of Patients reporting CNS (central nervous system) side effects of any severity
Change of Cholesterol Values From Baseline to Week 48, 96, 144 baseline to week 48, 96, 144 Changes frombaseline in total cholesterol, LDL-cholesterol(LDL-c) and HDL
Changes of Apolipoprotein Values From Baseline to Week 48, 96, 144 baseline to week 48, 96, 144 Changes frombaseline apolipoprotein A1 \& B
Change of hsCRP From Baseline to Week 48, 96, 144 baseline to week 48, 96, 144 Change of hsCRP from baseline to week 48, 96, 144
Change of Total Triglycerides From Baseline to Week 48, 96, 144 baseline to week 48, 96, 144 Change of total triglycerides from baseline to week 48, 96, 144
Change of Total Cholesterol to HDL-cholesterol Ratio From Baseline to Week 48, 96, 144 baseline to week 48, 96, 144 Change of Total cholesterol to HDL-cholesterol ratio from baseline to week 48, 96, 144
Proportion of Patients With VL < 50 Copies/ml From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT VL \<50 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT) for the patient
Proportion of Patients With VL < 400 Copies/ml From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT VL \<400 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT)
Change in CD4+ Count From Baseline From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT Change in CD4+ cell count from baseline among patients on treatment at each visit, with the final visit at Week 144 or EOT
Change in Framingham Score From Baseline From baseline to Weeks 48, 96 and 144/EOT Change in the estimated risk of cardiovascular disease using the Framingham algorithm from baseline to after 48, 96 and 144 weeks, last observation carried forward (LOCF). The score is based on age, gender, systolic blood pressure, total cholesterol, high density lipoprotein cholesterol and smoking status. Scores range from 0 to 21 with higher scores indicating a greater risk.
Change in Mental Health Summary (MHS) Score From Baseline From baseline to Weeks 48, 96 and 144/EOT Quality of life (QoL) assessment by change in MHS score from baseline to after 48, 96 and 144 weeks (observed cases), from the Medical Outcomes Study HIV Health Survey (MOS-HIV), a 35-item self-administered questionnaire including 10 scales covering: health perceptions, pain, physical functioning, role functioning, social and cognitive functioning, mental health, energy/fatigue, health distress, and QoL. The MHS is a weighted average of the 10 scales and ranges from 0 to 100 with higher scores indicating better QoL.
Change in Physical Health Summary (PHS) Score From Baseline From baseline to Weeks 48, 96 and 144/EOT QoL assessment by change in PHS score from baseline to after 48, 96 and 144 weeks (observed cases), from the MOS-HIV, a 35-item self-administered questionnaire including 10 scales covering: health perceptions, pain, physical functioning, role functioning, social and cognitive functioning, mental health, energy/fatigue, health distress, and QoL. The PHS is a weighted average of the 10 scales and ranges from 0 to 100 with higher scores indicating better QoL.
Number of Patients Hospitalized From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT Cost effectiveness assessment by number of patients hospitalized
Non-scheduled Physician Visits From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT Cost effectiveness assessment by number of patients with non-scheduled physician visits
Treatment-emergent AIDS-defining Illness From baseline to Week 144 Treatment-emergent AIDS-defining illness (tr.-emerg. AIDS-def.illness) including worsening during treatment
Lipodystrophy From baseline to Week 144 Number of patients with AE lipodystrophy
Serum Lipid Abnormalities From baseline to Week 144 Number of patients with AE elevated serum lipids (i.e. hypercholesterolaemia)
Genotypic Resistance Associated With Virologic Failure From baseline to Week 48 Number of treatment-emergent drug-associated substitutions in patients with virological failure up to Week 48. The total number of genotypic mutations in those patients who were virologic failures is given, not the number of patients with mutations.
Treatment-emergent AIDS-defining Illness Leading to Death From baseline to Week 144 Patients with an AIDS-defining illness leading to death broken out by treatment. Statistical analysis shows time to death from AIDS-defining illness.
Glycaemic Abnormalities From baseline to Week 144 Number of patients with AE elevated serum glucose
Treatment Response at Week 96 From baseline to Week 96 Treatment response is defined as a viral load (VL) \<50 copies/mL measured at two consecutive visits prior to Week 96 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 96.
Treatment Response at Week 144 From baseline to Week 144 Treatment response is defined as a viral load (VL) \<50 copies/mL measured at two consecutive visits prior to Week 144 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 144.
Proportion of Patients With Virological Rebound With VL >=50 Copies/mL After CVR (Confirmed Virological Response) at Week 24, 48, 96, 144 at Week 24, 48, 96, 144 The analyses of virologic rebound were performed on the original values at each visit(ORGV) rather than calculated results within time windows (CAL)
Proportion of Patients With Virological Rebound With VL >=400 Copies/mL After CVR at Week 24, 48, 96, 144 at Week 24, 48, 96, 144 The analyses of virologic rebound were performed on the original values at each visit(ORGV) rather than calculated results within time windows (CAL)
Proportion of Patients With Virologic Failure at Week 48, 96, 144 at Week 48, 96, 144 Time to Treatment Response (First Confirmed VL<50 Copies/mL) baseline to week 144 Time to treatment response was defined as the time from start of treatment until the first measurement of the first confirmed virological response
Trial Locations
- Locations (68)
1100.1470.55001 Boehringer Ingelheim Investigational Site
🇲🇽Col. Toriello Guerra, Mexico
1100.1470.35103 Boehringer Ingelheim Investigational Site
🇵🇹Porto, Portugal
1100.1470.41002 Boehringer Ingelheim Investigational Site
🇨🇭Zürich, Switzerland
1100.1470.54004 Boehringer Ingelheim Investigational Site
🇦🇷Capital Federal, Argentina
1100.1470.54002 Boehringer Ingelheim Investigational Site
🇦🇷Córdoba, Argentina
1100.1470.54001 Boehringer Ingelheim Investigational Site
🇦🇷Rosario, Argentina
1100.1470.49014 Boehringer Ingelheim Investigational Site
🇩🇪Düsseldorf, Germany
1100.1470.49008 Boehringer Ingelheim Investigational Site
🇩🇪Erlangen, Germany
1100.1470.49001 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1100.1470.49018 Boehringer Ingelheim Investigational Site
🇩🇪Bonn, Germany
1100.1470.49035 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt, Germany
1100.1470.49037 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1100.1470.49016 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1100.1470.39010 Boehringer Ingelheim Investigational Site
🇮🇹Lecco, Italy
1100.1470.39004 Boehringer Ingelheim Investigational Site
🇮🇹Torino, Italy
1100.1470.49031 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1100.1470.49020 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany
1100.1470.39001 Boehringer Ingelheim Investigational Site
🇮🇹Bergamo, Italy
1100.1470.49034 Boehringer Ingelheim Investigational Site
🇩🇪München, Germany
1100.1470.49000 Boehringer Ingelheim Investigational Site
🇩🇪Ulm, Germany
1100.1470.55003 Boehringer Ingelheim Investigational Site
🇲🇽Tlalpan-México D,F, Mexico
1100.1470.34002 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1100.1470.34008 Boehringer Ingelheim Investigational Site
🇪🇸Badalona, Spain
1100.1470.39012 Ospedale Sant'Anna
🇮🇹Como, Italy
1100.1470.55004 Boehringer Ingelheim Investigational Site
🇲🇽Col Obregón, Mexico
1100.1470.48001 Boehringer Ingelheim Investigational Site
🇵🇱Chorzow, Poland
1100.1470.39009 Boehringer Ingelheim Investigational Site
🇮🇹Torrette Di Ancona, Italy
1100.1470.39007 Boehringer Ingelheim Investigational Site
🇮🇹Varese, Italy
1100.1470.40002 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
1100.1470.34013 Boehringer Ingelheim Investigational Site
🇪🇸Alcalá de Henares (Madrid), Spain
1100.1470.34009 Boehringer Ingelheim Investigational Site
🇪🇸L'Hospitalet de Llobregat, Spain
1100.1470.55008 Boehringer Ingelheim Investigational Site
🇲🇽Col. Los Filtros, San Luis Potosí, Mexico
1100.1470.34014 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1100.1470.44005 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1100.1470.44006 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1100.1470.34003 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1100.1470.34010 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1100.1470.34007 Boehringer Ingelheim Investigational Site
🇪🇸Sabadell (Barcelona), Spain
1100.1470.34004 Boehringer Ingelheim Investigational Site
🇪🇸San Sebastian, Spain
1100.1470.34019 Boehringer Ingelheim Investigational Site
🇪🇸Malaga, Spain
1100.1470.44002 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1100.1470.39003 Boehringer Ingelheim Investigational Site
🇮🇹Bologna, Italy
1100.1470.49036 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt am Main, Germany
1100.1470.49032 Boehringer Ingelheim Investigational Site
🇩🇪Würzburg, Germany
1100.1470.49002 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1100.1470.54003 Boehringer Ingelheim Investigational Site
🇦🇷Mar del Plata, Argentina
1100.1470.49003 Boehringer Ingelheim Investigational Site
🇩🇪Bochum, Germany
1100.1470.35101 Boehringer Ingelheim Investigational Site
🇵🇹Lisboa, Portugal
1100.1470.49033 Boehringer Ingelheim Investigational Site
🇩🇪Freiburg/Breisgau, Germany
1100.1470.49038 Boehringer Ingelheim Investigational Site
🇩🇪Magdeburg, Germany
1100.1470.55006 Boehringer Ingelheim Investigational Site
🇲🇽Aguascalientes, Mexico
1100.1470.39006 Boehringer Ingelheim Investigational Site
🇮🇹Ferrara, Italy
1100.1470.55007 Boehringer Ingelheim Investigational Site
🇲🇽Guadalajara Jal., Mexico
1100.1470.48002 Boehringer Ingelheim Investigational Site
🇵🇱Szczecin, Poland
1100.1470.48003 Boehringer Ingelheim Investigational Site
🇵🇱Bydgoszcz, Poland
1100.1470.34012 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1100.1470.34006 Boehringer Ingelheim Investigational Site
🇪🇸Santa Cruz de Tenerife, Spain
1100.1470.34015 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1100.1470.34011 Boehringer Ingelheim Investigational Site
🇪🇸Vigo, Spain
1100.1470.44004 Boehringer Ingelheim Investigational Site
🇬🇧Birmingham, United Kingdom
1100.1470.44001 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1100.1470.44003 Boehringer Ingelheim Investigational Site
🇬🇧Manchester, United Kingdom
1100.1470.41001 Boehringer Ingelheim Investigational Site
🇨🇭Lugano, Switzerland
1100.1470.41003 Boehringer Ingelheim Investigational Site
🇨🇭St. Gallen, Switzerland
1100.1470.48004 Boehringer Ingelheim Investigational Site
🇵🇱Warsaw, Poland
1100.1470.35102 Boehringer Ingelheim Investigational Site
🇵🇹Cascais, Portugal
1100.1470.40001 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
1100.1470.41004 Boehringer Ingelheim Investigational Site
🇨🇭Bern, Switzerland