TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.

Over the past decade, anti-human immunodeficiency virus (HIV) drugs have been introduced
sequentially for use in the clinic. Currently, patients are routinely being treated with 3
or 4 drug combinations including nucleoside/tide analogue reverse transcriptase inhibitors
(NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease
inhibitors (PIs), and/or fusion inhibitors. New potent antiretroviral (ARV) compounds that
work in people whose HIV-1 virus is resistant to available drugs are urgently needed. This
is a Phase III, randomized (study medication is assigned by chance), double-blind (neither
the study physician nor the patient knows the name of the study assigned medication),
double-dummy, active-controlled trial to compare the effectiveness, safety, and ability to
tolerate TMC278 versus efavirenz (EFV). The study will last for 104 weeks which includes a
screening period of 4 weeks, a 96-week treatment period, followed by a 4 week follow-up
period. Patients will be randomly assigned to TMC278 or to efavirenz, either of these
treatments will be in combination with two other anti-HIV drugs (2 NRTIs: emtricitabine
(FTC) + tenofovir (TDF)). TDF/FTC will be administered as a fixed dose combination if
available. The hypothesis to be provided in this study is that the investigational drug
TMC278 will perform just like efavirenz (EFV) in terms of antiviral effectiveness (i.e.,
suppressing of the plasma viral load to a level < 50 HIV-1 RNA (ribonucleic acid) copies/mL)
in ARV-naïve HIV-infected patients. During the trial, patients' health will be monitored by
physical examination, interview to assess health and well being, and laboratory testing on
blood and urine samples. Experimental Group: One tablet of TMC278 25 mg once daily plus one
tablet of placebo once daily that looks just like efavirenz (EFV) plus
tenofovir/emtricitabine; Control Group: One tablet of Placebo once daily that looks just
like TMC278 plus EFV 600 mg once daily plus tenofovir/emtricitabine.

Inclusion Criteria:

- Patient with documented HIV-1 infection

- Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to
screening

- Patient's HIV-1 plasma viral load at screening is > 5,000 HIV-1 RNA copies/mL
(assayed by RNA PCR standard specimen procedure)

- Patient's virus is sensitive to TDF and FTC

- Patient agrees not to start ART (antiretroviral treatment) before the baseline visit

Exclusion Criteria:

- Previous use of ANY ARV drug for ANY length of time

- Any documented evidence of NNRTI resistance associated mutations in patient's HIV

- Category C AIDS defining illness, except: stable Kaposi Sarcoma, wasting syndrome if
not progressive

- Pneumocystis carinii pneumonia (PCP) that is considered not cured

- Active TB

- Allergy or hypersensitivity to study or background ARTs

- Specific grade 3 or 4 toxicity

- Kidney impairment: calculated creatinine clearance <50 ml/min