This is a First-in-Human Phase I, double-blind (neither physician or patient knows the name of the assigned study drug), randomized (study medication assigned by chance), placebo-controlled trial for TMC558445 to examine the safety, tolerability and plasma pharmacokinetics after increasing single oral doses of TMC558445 and after increasing oral repeated doses of TMC558445, followed by a single day dosing of TMC558445 and TMC310911. This combination will assess the potential pharmacokinetic enhancement (boosting) on the latter compound. TMC558445 is to be used as a booster for TMC310911. The trial consists of 2 parts: a single dose escalation and a multiple dose escalation part. The single dose escalation part will consist of 6 sessions. The single dose part will include 18 healthy adult volunteers, divided over 2 panels. In each session, 6 healthy volunteers will receive TMC558445 and 3 healthy volunteers will receive placebo with standard meals. Intake of TMC558445/placebo will take place on Day 1 of each session between 07:00 and 11:00 a.m. Single doses of 40, 100, 200, 400, 800, and 1600 mg of TMC558445/placebo will be administered alternating over the 2 panels. The trial will be stopped earlier when the maximum tolerated dose is reached. A washout period (a period where no treatment will be taken in view of having all the medication eliminated from the body before starting a new treatment) of at least 10 days will be respected between consecutive TMC558445/placebo dosings. Once, a food effect will be studied under fasted conditions at one of the previously studied doses. The multiple dose escalation part of this trial will start when the 200 mg dose is found to be safe.This part of the trial will include 27 healthy adult volunteers, divided over 3 panels: 6 will receive TMC558445 and 3 will receive placebo. TMC558445/placebo will be administered during 7 consecutive days. The treatment will be twice daily between 07:00 and 11:00 a.m. and between 07:00 and 11:00 p.m. Volunteers will receive a single oral dose of 300 mg of TMC310911 on Day 7 and on Day 1 of Session XI (after a washout period of at least 14 days). Dose escalation in the single and multiple ascending dose regimens will continue only if the previous dose was found safe. Pharmacokinetic profiles of TMC558445 will be determined up to a max of 72 h after the last intake per session. Pharmacokinetic profiles of TMC310911 will be determined over 24 h. The expected duration of the investigational period in the single escalation dose part is at least 8 weeks and at least 3 weeks in the multiple escalation dose part. Safety and tolerability evaluations will be recorded at regular intervals throughout the trial. Blood and urine samples will be taken at predefined timings as well as ECG measurements, vital signs (blood pressure and heart rate), and physical examinations. The study has been amended. In Panel 5, TMC558445 may now be administered either twice daily or once daily and TMC310911 may be given at a 300 mg or 600 mg single dose. Decision on dosing regimen, TMC310911 dose and food conditions will be made based on results of the previous panels.