Phase 3
N=569
Nevirapine or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir in Human Immunodeficiency Virus (HIV)-1-infected Treatment Naive Adults
HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT00389207 ↗Enrolled (actual)
569
Serious AEs
14.6%
Results posted
Mar 2012
Primary outcome: Primary: Treatment Response at Week 48 — 126; 124; 250; 126 Patients — p=0.684
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- nevirapine bid (Drug); nevirapine qd (Drug); atazanavir (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Feb 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Treatment Response at Week 48 |
126; 124; 250; 126; 62; 64 | 0.684 |
| SECONDARY Treatment Response at Week 48 (TLOVR Algorithm) |
261; 142; 115; 51 | 0.321 |
| SECONDARY Proportion of Patients With VL < 50 Copies/ml |
0.107; 0.09; 0.304; 0.25; 0.515; 0.412 | — |
| SECONDARY Proportion of Patients With VL < 400 Copies/ml |
0.365; 0.287; 0.714; 0.679; 0.856; 0.834 | — |
| SECONDARY Change in CD4+ Count From Baseline |
77.2; 86.1; 105.6; 98.0; 120.3; 110.9 | — |
| SECONDARY Change in Framingham Score From Baseline |
0.50; 0.66; 0.93; 1.19; 1.14; 0.82 | — |
| SECONDARY Change in Mental Health Summary (MHS) Score From Baseline |
6.09; 4.52; 6.10; 4.89; 4.76; 4.70 | — |
| SECONDARY Change in Physical Health Summary (PHS) Score From Baseline |
3.34; 3.35; 3.19; 3.00; 2.22; 3.35 | — |
| SECONDARY Number of Patients Hospitalized |
8; 2; 6; 5; 5; 5 | — |
| SECONDARY Non-scheduled Physician Visits |
74; 35; 45; 35; 58; 28 | — |
| SECONDARY Genotypic Resistance Associated With Virologic Failure |
21; 0; 11; 0; 34; 0 | — |
| SECONDARY Treatment-emergent AIDS-defining Illness |
26; 7; 350; 186 | — |
| SECONDARY Treatment-emergent AIDS-defining Illness Leading to Death |
3; 0; 373; 193 | 0.0403 sig |
| SECONDARY Lipodystrophy |
1; 1; 375; 192 | — |
| SECONDARY Serum Lipid Abnormalities |
9; 4; 367; 189 | — |
| SECONDARY Glycaemic Abnormalities |
0; 3; 376; 190 | — |
| SECONDARY Treatment Response at Week 96 |
131; 122; 253; 149; 57; 66 | 0.0109 sig |
| SECONDARY Treatment Response at Week 144 |
121; 113; 234; 143; 67; 75 | 0.0031 sig |
| SECONDARY Proportion of Patients With Virological Rebound With VL >=50 Copies/mL After CVR (Confirmed Virological Response) at Week 24, 48, 96, 144 |
3; 2; 5; 5; 4; 5 | — |
| SECONDARY Proportion of Patients With Virological Rebound With VL >=400 Copies/mL After CVR at Week 24, 48, 96, 144 |
2; 2; 4; 2; 3; 3 | — |
| SECONDARY Proportion of Patients With Virologic Failure at Week 48, 96, 144 |
20; 25; 45; 25; 15; 25 | 0.9784 |
| SECONDARY Time to Treatment Response (First Confirmed VL<50 Copies/mL) |
12.00; 12.14; 12.00; 23.71 | 0.0002 sig |
| SECONDARY Time to Loss of Virologic Response (Rebound) |
143.86; 143.21; 143.71; 143.00 | 0.1329 |
| SECONDARY Time to Treatment Failure |
143.86; 143.21; 143.71; 143.00 | 0.0444 sig |
| SECONDARY Change in the Calculated Glomerular Filtration Rate (GFR) at Week 48, 96 and 144 |
-3.91; -5.92; -4.86; -7.18; -6.93; -10.02 | — |
| SECONDARY Proportion of Patients With >= DAIDS Grade 2 Laboratory Abnormalities |
74; 84; 72; 30; 28; 39 | — |
| SECONDARY Proportion of Patients Reporting Rash of Any Severity |
75; 64; 74 | — |
| SECONDARY Proportion of Patients Reporting Hepatic Events of Any Severity |
26; 24; 92 | — |
| SECONDARY Proportion of Patients Reporting CNS (Central Nervous System) Side Effects of Any Severity |
41; 41; 37 | — |
| SECONDARY Change of Cholesterol Values From Baseline to Week 48, 96, 144 |
29.28; 29.54; 20.84; 39.17; 36.87; 29.99 | — |
| SECONDARY Changes of Apolipoprotein Values From Baseline to Week 48, 96, 144 |
0.23; 0.23; 0.08; 0.23; 0.23; 0.07 | — |
| SECONDARY Change of hsCRP From Baseline to Week 48, 96, 144 |
-1.01; -0.67; -0.70; -1.54; -0.79; 0.35 | — |
| SECONDARY Change of Total Triglycerides From Baseline to Week 48, 96, 144 |
0.08; 1.67; 36.28; 9.34; 5.35; 30.45 | — |
| SECONDARY Change of Total Cholesterol to HDL-cholesterol Ratio From Baseline to Week 48, 96, 144 |
-0.37; -0.33; 0.20; -0.22; -0.25; 0.28 | — |
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
- 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 = 50 ml/min according to the Cockcroft-Gault formula
- Karnofsky score >= 70
- Acceptable medical history, as assessed by the investigator
Exclusion criteria
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
Data sourced from ClinicalTrials.gov (NCT00389207). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.