TMC278-C204: TMC278 in Treatment Naive HIV-1 Infected Subjects

• To evaluate antiviral activity of 96 weeks
• To evaluate safety and tolerability of TMC278
• To compare safety and efficacy with the control group
• To evaluate immunologic changes
• To evaluate changes in viral genotype and drug susceptibility
• To evaluate the pharmacokinetics of TMC278

This is a study of a new, experimental Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) called TMC278. The study will help determine a safe and effective dose of this new drug.

This is a study of a new, experimental Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) called TMC 278. The study will help determine a safe and effective dose of this new drug. People included in this study will be treatment naive, which means they have not previously received treatment with antiretroviral therapy, or have been treated for a maximum of 2 weeks with licensed protease inhibitors (PIs) or nucleoside reverse transcriptase inhibitor (NRTIs).

The study will last for 152 weeks. This includes a 4-week screening period, a 144-week treatment period and a 4-week follow-up period. Three different doses of TMC 278 will be compared to efavirenz. HIV infected subjects will be randomly assigned (like tossing a coin) to TMC278 or to efavirenz in combination with two other anti-HIV drugs (fixed backbone) selected by the participant's doctor. Three different doses of TMC278 in the partially blinded part of the trial. In open-label part only one dose (75mg).;

• Drug: TMC278
  150mg once daily for 96 weeks
• Drug: TMC278
  25mg once daily for 96 weeks
• Drug: Efavirenz
  600mg Efavirenz once daily for 144 weeks
• Drug: TMC278
  75mg once daily from 96 weeks to 144 weeks
• Drug: TMC278
  75mg once daily for 96 weeks

• Experimental: 001
  TMC278 25mg once daily for 96 weeks
  Intervention: Drug: TMC278
• Experimental: 002
  TMC278 75mg once daily for 96 weeks
  Intervention: Drug: TMC278
• Active Comparator: 005
  Efavirenz 600mg Efavirenz once daily for 144 weeks
  Intervention: Drug: Efavirenz
• Experimental: 004
  TMC278 75mg once daily from 96 weeks to 144 weeks
  Intervention: Drug: TMC278
• Experimental: 003
  TMC278 150mg once daily for 96 weeks
  Intervention: Drug: TMC278

Inclusion Criteria:

• Documented HIV-1 infection
• Plasma viral load at screening visit above 5000 HIV-1 RNA copies/ml
• Never been treated with an antiretroviral (ARV) drug or therapeutic HIV vaccine, or have received < 2 week's treatment with an NRTI and/or PI prior to screening
• Agree not to start ARV treatment before the baseline visit

Exclusion Criteria:

• Subject has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness except stable, cutaneous Kaposi's Sarcoma or Wasting Syndrome due to HIV infection
• Clinically significant disease (e.g., pancreatitis, cardiac dysfunction)
• Subject has known or suspected acute (primary) HIV-1 infection
• Any prior use of NNRTIs for > 2 weeks
• Acute hepatitis A, B, or C infection
• Receipt of any investigational drug within 90 days prior to trial initiation and first dosing of study medication
• Pregnant or breastfeeding female
• Males or Females not willing to take the recommended precautions to avoid pregnancy during the trial
• Any grade 3 or 4 toxicity according to the Division of AIDS (DAIDS) grading severity list except for isolated grade 3 elevations of gamma glutamyl transferase (GGT)
• Tuberculosis
• History of or currently active alcohol or drug use which in the opinion of the investigator will likely compromise subjects' safety and/or compliance with trial procedures