A Study to Assess the Long-term Safety and Tolerability of TMC114/Rtv in HIV-1 Infected Participants After Rolling-over From Other TMC114 Trials

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was primarily to assess the long-term safety and tolerability of TMC114/rtv in addition to an individually optimized background antiretroviral therapy in HIV-1 infected participants. In addition, antiviral activity and immunological effect were also evaluated.

Detailed Description
-----------------
This was a phase II, open label, multicenter trial of an investigational protease inhibitor TMC114 in the presence of ritonavir (rtv) in HIV-1 infected participants who were randomized in trials TMC114-C201, TMC114-C207 or in sponsor selected phase I trials and who might derive benefit from TMC114 therapy, as judged by the investigator. The trial consisted of a screening period of a maximum of 4 weeks, a 96-week treatment period and a 4-week follow-up period. The maximal trial duration for each participant was104 weeks. During the treatment period, all participants were receiving TMC114 in combination with RTV, orally, as 600/100 mg dose twice daily, in addition to an individually optimized background regimen of antiretroviral (ARV) therapy, selected by the investigator at a baseline of the study. Sponsor provided a follow-up treatment with TMC114 for all participants who continued to benefit from treatment with TMC114/RTV until it became commercially available for the participant. Participants, who completed the 96 weeks of treatment period with TMC114, had the opportunity to roll over to the extension of this trial, if TMC114 was not locally commercially available.

Official Title
-----------------
An Open Label Trial of TMC114/Rtv in HIV-1 Infected Subjects Who Were Randomized in the Trials TMC114-C201, TMC114-C207 or in Sponsor Selected Phase I Trials

Conditions
-----------------
HIV

Intervention / Treatment
-----------------
* Drug: TMC114
* Drug: rtv


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Must be diagnosed with HIV Previously randomized in trials TMC114-C201, TMC114-C207 or in sponsor selected Phase I trials Agreed to take at least 2 antiretroviral agents from baseline onwards Could comply with the protocol requirements General medical condition, in the investigator's opinion, was not interfering with the assessments and the conduct of the trial Exclusion Criteria: A disallowed concomitant therapy Current or past history of active alcohol and/or drug use Pregnant or breast-feeding females Any active or unstable medical condition (e.g., tuberculosis; cardiac dysfunction; pancreatitis; acute viral infections) Clinical or laboratory evidence of active liver disease, liver impairment/dysfunction or cirrhosis Clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication Laboratory abnormalities at screening (criteria variable according to the test)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMC114 + rtv<br>Every participant recieves 2 tablets of TMC114, 300 mg, combined with one tablet of rtv (ritonavir), 100mg, orally twice daily, every 12 hours | Drug: TMC114<br>* 300 mg tablets of TMC114 ethanolate with microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, and Opadry® Orange<br>Drug: rtv<br>* 100 mg tablet of Norvir®<br>* Other names: Norvir;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability of TMC114/RTV 600/100 mg combination |  | Baseline, up to the end of follow-up period (approximatelly 100 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with HIV-1 plasma viral load level <50 copies/mL (TLOVR, non-VF censored) | The Time to Loss of Virologic Response (TLOVR) algorithm will be used to derive response. Response will be confirmed at 2 consecutive visits and participants who discontinue will be considered nonresponders after discontinuation. Resuppression after confirmed virologic failure will be considered as failure. Virologic Failure will include participants who are rebounders (ie, confirmed viral load >= 50 copies/mL after being a responder) or who were never suppressed (no confirmed viral load <50 copies/mL); non-VF censored: participants who discontinue treatment due to reason other than Virologic Failure will be excluded. | Week 48, Week 96 | 
| Change in CD4 cells absolute count | The immunologic change will be determined by changes in absolute values for CD4 cells. | Week 48, Week 96 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ritonavir, HIV, AIDS, TMC114, Norvir, Darunavir