NCT00389207 - Nevirapine or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir in Human Immunodeficiency Virus (HIV)-1-infected Treatment Naive Adults | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Treatment Response at 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.

Time frame: From baseline to Week 48

Secondary Outcomes

Treatment Response at Week 48 (TLOVR Algorithm)

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 frame: From baseline to Week 48

Proportion of Patients With VL < 50 Copies/ml

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

Time frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

Proportion of Patients With VL < 400 Copies/ml

VL \<400 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT)

Time frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

Change in CD4+ Count From Baseline

Change in CD4+ cell count from baseline among patients on treatment at each visit, with the final visit at Week 144 or EOT

Time frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

Change in Framingham Score From Baseline

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.

Time frame: From baseline to Weeks 48, 96 and 144/EOT

Change in Mental Health Summary (MHS) Score From Baseline

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.

Time frame: From baseline to Weeks 48, 96 and 144/EOT

Change in Physical Health Summary (PHS) Score From Baseline

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.

Time frame: From baseline to Weeks 48, 96 and 144/EOT

Number of Patients Hospitalized

Cost effectiveness assessment by number of patients hospitalized

Time frame: From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT

Non-scheduled Physician Visits

Cost effectiveness assessment by number of patients with non-scheduled physician visits

Time frame: From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT

Genotypic Resistance Associated With Virologic Failure

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.

Time frame: From baseline to Week 48

Treatment-emergent AIDS-defining Illness

Treatment-emergent AIDS-defining illness (tr.-emerg. AIDS-def.illness) including worsening during treatment