TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

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 (like tossing a coin) to TMC278 or to efavirenz
in combination with two other anti-HIV drugs of the class nucleoside/nucleotide reverse
transcriptase inhibitors. 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 daily; plus efavirenz (EFV) placebo; plus 2 nucleoside/nucleotide
reverse transcriptase inhibitors; Control Group: One tablet of Placebo daily that looks just
like TMC278 plus EFV 600 mg daily plus 2 nucleoside/nucleotide reverse transcriptase
inhibitors for 104 weeks.

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 the 2 nucleoside/nucleotide reverse transcriptase
inhibitors chosen for treatment

- Patient agrees not to start ART before the baseline visit

- Patient is HLA-B*5701 negative in case abacavir is included in the patient's
treatment regimen.

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