VERxVE Study on Efficacy and Safety of Nevirapine XR in Comparison to Nevirapine IR With Truvada in Naive HIV+ Patients

• Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population [ Time Frame: week 0 to 144 ] [ Designated as safety issue: No ]
• Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population [ Time Frame: week 144 ] [ Designated as safety issue: No ]
  Endpoint was the number of patients with a sustained virologic response through week 144 using LLOQ = 50 copies/mL
• Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population [ Time Frame: week 0 to 144 ] [ Designated as safety issue: No ]
• Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Observed Cases, Full Analysis Set Population [ Time Frame: baseline, week 144 ] [ Designated as safety issue: No ]
• Comparison of CD4 Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Observed Cases, Full Analysis Set Population [ Time Frame: baseline, week 144 ] [ Designated as safety issue: No ]

The primary objective of this study is to evaluate the efficacy of 400 mg QD nevirapine extended release (NVP XR) formulation versus 200 mg BID nevirapine immediate release (NVP IR) in ARV therapy naïve HIV-1 infected patients after 48 weeks of treatment. Secondary objectives are to evaluate safety and pharmacokinetics of NVP XR and NVP IR.

• Drug: nevirapine IR
  200 mg BID
• Drug: nevirapine XR
  400 mg QD

• Experimental: nevirapine XR
  400 mg QD
  Intervention: Drug: nevirapine XR
• Active Comparator: nevirapine IR
  200 mg BID
  Intervention: Drug: nevirapine IR

Inclusion criteria:

1. Signed informed consent in accordance with Good Clinical Practice and local regulatory requirements prior to trial participation
2. HIV-1 infected males or females >= 18 years of age with positive serology (ELISA) confirmed by Western blot
3. No previous antiretroviral treatment
4. Males with CD4+ counts >50 - <400 cells/ml or females with CD4+ counts >50-<250 cells/ml

5. Adequate renal function defined as a calculated creatinine clearance (CLCr) greater than or equal to 50 mL/min according to the Cockcroft-Gault formula as follows:

   Male: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in mg/dl) = CLCr (mL/min).

   Female: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in mg/dl) x 0.85 = CLCr (mL/min).

6. Karnofsky score >70 (see Appendix 10.4)
7. An HIV-1 viral load of 1,000 copies/mL
8. Willingness to initiate CD4+ cell count-guided chemoprophylaxis to prevent important opportunistic infections as defined in Appendix 10.2
9. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system (listed in Appendix 10.3) during the study.
10. For centers participating in the PK substudy only: Written informed consent in accordance with GCP and local legislation for participation in the PK substudy. Refusal to participate in the PK substudy is not an exclusion criterion for participation in the trial. Only study centers with previous experience and equipped in handling PK samples are eligible for participation in the substudy.

Exclusion criteria:

1. Active drug abuse or chronic alcoholism at the investigator's discretion
2. Active hepatitis B or C disease, defined as HBsAg-positive and HBV-DNA-positive or HCV-RNA-positive
3. Female patients of child-bearing potential who: are pregnant at screening; 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 Note: During participation in this study, females and males have to use barrier methods of contraception in addition or instead of ethinyl estradiol containing oral contraceptives.
4. Laboratory parameters >DAIDS Grade 2
5. ALT/AST > DAIDS Grade 1
6. Hypersensitivity to any ingredients of the test products
7. Previous use of Viramune® (nevirapine) or any other antiretroviral agents (does not include use of single dose NVP for the prevention of mother to child transmission)
8. Resistance to NNRTIs or either one of the components of Truvada® (emtricitabine or tenofovir disoproxil fumarate) or lamivudine (3TC) based on HIV-1 genotypic resistance testing report obtained at screening
9. Patients who are receiving other concomitant treatments which are not permitted, as described in the prescribing information
10. Use of investigational medications (any experimental agent other than the study regimen) within 30 days before study entry or during the trial
11. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2)
12. Patients who have been diagnosed with malignant disease
13. Patients who in the opinion of the investigator are not candidates for inclusion in the study
14. Patient with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma
15. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit