A Phase I, open-label, single-sequence drug-drug interaction trial in subjects on stable methadone maintenance therapy, to investigate the potential interaction between TMC278 25 mg q.d. and methadone, at steady-state.

1. Male or female, aged between 18 and 55 years, extremes included;
2. Body Mass Index of 18.0 to 35.0 kg/m2, extremes included;
3. Informed Consent Form signed voluntarily before first trial-related activity;
4. Receiving once daily oral methadone maintenance therapy at a stable individualized dose;
5. The subject agrees:
- not to change the current methadone dose from screening until Day 11 included;
- to have a daily observed and documented methadone intake from Day *14 until Day 12, and a daily observed and documented TMC278 intake from Day 1 until Day 11;
6. Able to comply with protocol requirements;
7. The subject has obtained approval from his/her addiction physician for the subject*s participation in this trial. Furthermore, the addiction physician agrees to provide medical care for the subject after discharge from trial center;
8. General medical condition, in the investigator*s opinion, does not interfere with the assessments and the completion of the trial;
9. Otherwise healthy on the basis of screening

1. A positive HIV 1 or HIV 2 test at trial screening.
2. Female, except if postmenopausal since more than 2 years, or posthysterectomy, or post surgical sterilization (without reversal operation).
3. Evidence of current use of barbiturate, amphetamine, recreational drugs or opioids, with the exception of methadone.
4. Current use of alcohol, which in the investigator*s opinion would compromise subject*s safety and/or compliance with the trial procedures.
5. Hepatitis A infection at screening.
6. Decompensated liver function
7. Currently active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric (other than drug dependency), metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease.
8. Significant heart abnormalities.
9. Current or history of adrenal disorder.
10. Currently significant diarrhea, gastric stasis, or constipation (other than the pharmacodynamic effects of methadone) that in the investigator*s opinion could influence drug absorption or bioavailability.
11. Any history of significant skin disease such as, but not limited to, drug rash or eruptions, drug allergies, food allergy, dermatitis, eczema, psoriasis, or urticaria.
12. Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication administered in this trial (i.e. TMC278).
13. Previous experience of clinically significant hypersensitivity to methadone hydrochloride.
14. Use of disallowed concomitant therapy during the 14 days prior to the first dose of TMC278. Concomitant therapy that is not disallowed should not be changed between Day -14 and Day 11, except for ibuprofen and paracetamol.
15. Having previously participated in more than 1 trial (single or multiple dose) with TMC125, TMC120 and/or TMC278 (formerly known as R278474) or having developed a rash, erythema or urticaria while participating in a trial with the aforementioned compounds.
16. Lack of good/reasonable venous access.
17. Participation in an investigational drug trial within 60 days prior to Day -14.
18. Donation of blood or plasma or significant blood loss within 60 days prior to Day -14.
19. Any laboratory abnormalities at screening which could be of influence on the study.