This is a Phase II/III, open-label, roll-over trial to evaluate the long term safety and tolerability of TMC125, administered as part of an individually optimized antiretroviral therapy, in HIV 1 infected subjects. In addition, the antiviral activity and immunological effect of TMC125 as part of an antiretroviral regimen over time, and the evolution of HIV phenotype and genotype will be evaluated. Subjects who were randomized to an active control arm of any sponsor-selected TMC125 trial and virologically failed or completed the entire treatment period and who may derive benefit from TMC125 treatment as judged by the investigator can be enrolled. Based on the currently selected studies, a maximum of 60 subjects will be enrolled in the current trial. A dose of 800 mg of TMC125 twice a day (b.i.d.) will be given in combination with an investigator-selected, optimized underlying therapy starting at baseline and consisting of at least 2 drugs (nucleoside reverse transcriptase inhibitors [NRTIs] and/or allowed protease inhibitors [PIs] and/or enfuvirtide [T 20]) for 48 weeks. Tolerability and safety will be assessed throughout the trial. The efficacy parameters will be determined at defined time points during the trial. The trial will involve a screening visit on the same day as the withdrawal visit of the sponsor-selected trial, a baseline visit, a treatment period of 48 weeks, a final visit and a 4 week follow-up period.

Condition	Treatment or Intervention	Phase
HIV Infection	Drug: TMC125	Phase II

Further Study Details: 

Primary Outcomes: The primary objective of the trial is to evaluate the long-term safety and tolerability of TMC125.
Secondary Outcomes: The secondary objectives are to evaluate the antiviral activity and immunological effect of TMC125 as part of an antiretroviral (ARV) regimen over time, and to evaluate genotypic and phenotypic changes over time.
Expected Total Enrollment:  40

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Subject has signed the Informed Consent Form (ICF) voluntarily;
• Male or female subject, aged 18 years and above;
• Subject having previously been randomized to an active control arm of a sponsor selected TMC125 trial and has completed the entire treatment period or has met the definition of virological failure, as defined in the original protocol, before TMC125 C211 screening; Subject agrees to take TMC125 in combination with the investigator-selected combination therapy consisting of at least 2 drugs (NRTIs and/or allowed PI and/or T-20; low-dose ritonavir [≤ 400 mg daily dose] is not counted as a separate ARV);
• Subject can comply with the protocol requirements;
• Subject’s general medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial.

Exclusion Criteria:

• History of or currently active alcohol or substance use which in the investigator’s opinion would likely compromise the subject’s safety or compliance with the study procedures
• Any active clinically significant disease (e.g., tuberculosis, cardiac dysfunction) or findings during physical examination that, in the investigator’s opinion, would compromise the subject’s safety
• Renal impairment as defined by serum creatinine > 2 x upper limit of normal (ULN);
• Any grade 3 or grade 4 toxicity according to the AIDS Clinical Trial Group (ACTG) grading severity list (except for grade 3 glucose and asymptomatic triglyceride/cholesterol grade 3 or 4 elevations; or asymptomatic and isolated grade 3 or 4 elevations in gamma-glutamyl transferase [GGT] with all other liver enzymes and bilirubin within normal ranges, or isolated grade 3 elevation in amylase with no increase in lipase and no history of pancreatitis);
• Subjects with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (International Normalized Ratio > 1.3 or albumin < 30 g/l or direct bilirubin > 2.5 x ULN).

Arizona
      Body Positive, Inc., Phoenix,  Arizona,  85006,  United States
California
      UCLA Men's Health Program, Los Angeles,  California,  90024,  United States
      Tower ID Medical Associates, Los Angeles,  California,  90048,  United States
      Peter Ruane, MD, Los Angeles,  California,  90036,  United States
Connecticut
      Circle Medical LLC, Norwalk,  Connecticut,  06903,  United States
District of Columbia
      Whitman-Walker Clinic, Washington,  District of Columbia,  20009,  United States
      Dupont Circle Physicians Group, Washington,  District of Columbia,  20009,  United States
Florida
      Orlando Immunology Center, Orlando,  Florida,  32803,  United States
      University of South Florida, Tampa,  Florida,  33602,  United States
Illinois
      Northstar Medical Center, Chicago,  Illinois,  60657,  United States
Kentucky
      University of Kentucky School of Medicine, The Adult Infectious Diseases Division, Lexington,  Kentucky,  40536,  United States
Maryland
      Johns Hopkin's Hospital Divison of Infectious Diseases, Baltimore,  Maryland,  21205,  United States
Massachusetts
      Community Research Initiative of New England, Springfield,  Massachusetts,  01107,  United States
Michigan
      Henry Ford Health System, Dept. of Infectious Diseases, Detroit,  Michigan,  48202,  United States
New Jersey
      Saint Michael's Medical Center Infectious Diseases, Newark,  New Jersey,  07102,  United States
New York
      Jacobi Medical Center, Bronx,  New York,  10461,  United States
      Universityo of Rochester Medical Center, Infectious Disease Center, Rochester,  New York,  14642,  United States
North Carolina
      Duke University Health System, Division of Infectious Diseases, Durham,  North Carolina,  27710,  United States
Oregon
      Department of Research & Education, Portland,  Oregon,  97209,  United States
Texas
      University of Texas Houston Medical School Division of Infectious Diseases, Houston,  Texas,  77030,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555,  United States
      Therapeutic Concepts, Houston,  Texas,  77004,  United States
Washington
      Northwest Medical Specialties, Tacoma,  Washington,  98405,  United States

Study ID Numbers:  TMC125-C211
Record last reviewed:  July 2004
Last Updated:  May 19, 2005
Record first received:  May 18, 2005
ClinicalTrials.gov Identifier:  NCT00111280
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-05-24