A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Etravirine Administered in Combination With Other Antiretroviral Agents in Antiretroviral Treatment-Experienced HIV-1 Infected Patients

This is an open-label (all people involved know the identity of the intervention), single
arm, multicenter Phase IV study to evaluate the safety, tolerability, and pharmacokinetics
of etravirine (ETR) in combination with antiretroviral (ARV) therapy other than darunavir
(DRV) + ritonavir (rtv). In addition, the antiviral activity and the
pharmacokinetic/pharmacodynamic profile, and safety of ETR will be assessed. The study will
consist of a screening period of maximum 6 weeks, a baseline visit, and a 48-week treatment
period. After the end of the treatment period, patients with ongoing adverse events (AEs)
will be followed for an additional 4 weeks. At least 200 ARV treatment-experienced human
immunodeficiency virus (HIV-1) infected patients will be enrolled in this study. Patients
will be considered ARV treatment-experienced if they have been on their current stable
highly active antiretroviral therapy (HAART) regimen for at least 8 weeks prior to
screening. The study population will consist of patients who need to change their current
HAART regimen due to any of the following reasons: (1) patients experiencing virologic
failure (with a screening viral load value >=500 HIV-1 RNA copies/mL), or (2) patients
switching due to simplification of their current regimen or due to AEs and/or tolerability
reasons (with a screening viral load value <50 HIV-1 RNA copies/mL). Patients will receive
ETR 200 mg twice daily in combination with an investigator-selected background regimen. In
addition to ETR, which needs to be active based on resistance testing, the background
regimen should consist of at least 1 active ARV resulting in a treatment regimen with at
least 2 active ARVs. The following exceptions to this are: (1) if raltegravir (RAL) or
atazanavir/ritonavir (ATV/rtv) are part of the background regimen, the number of active ARVs
in this background regimen should be at least 2; (2) low-dose ritonavir should not be
counted as an active ARV. DRV/rtv will not be allowed in the background regimen in order to
evaluate the safety and pharmacokinetics of ETR in combination with ARVs other than DRV/rtv.
Furthermore, a background regimen consisting of nucleoside transcriptase inhibitors (NRTIs)
only will not be allowed. The background regimen cannot be modified until the end of the
treatment period with the following exception: switches within the ARV class will be allowed
for well documented tolerability/toxicity reasons. For patients who, in the opinion of the
investigator, are deriving clinical benefit from ETR, and to whom ETR is not commercially
available in his/her country, is not reimbursed or cannot be accessed from another source
(e.g., access program, government program) in the region the patient is living in, the
possibility to extend their ETR treatment period will be provided. The ETR tablets are to be
taken orally twice daily after a meal. A total daily dose of 400 mg is to be taken for 48
weeks.

Inclusion Criteria:

- Documented HIV-1 infection.

- Treatment with current stable HAART for at least 8 weeks prior to screening.

- Currently experiencing virologic failure (screening viral load value >=500 HIV-1 RNA
copies /mL), or switching due to simplification of their regimen or due to adverse
event or tolerability reasons, (screening viral load value <50 HIV-1 RNA copies /mL).

- Demonstrated sensitivity to etravirine and to at least 1 antiretroviral (ARV) agent
in the background regimen, based on the resistance test at screening or resistance
history or have previously received treatment with etravirine.

- Patients agree not to have unprotected sex while on the study.

- No currently active AIDS-defining illness.

- Did not take any non-ARV investigational agents within 90 days prior to screening.

- No use of disallowed treatments.

- Adequate liver function.

Exclusion Criteria:

- Any currently active illness or toxicity due to HIV infection.

- Any active clinically significant disease or findings during screening of medical
history or physical examination that, in the investigator's opinion, would compromise
the patient's safety or outcome of the study.