Safety and Immune Response to Vicriviroc in Combination Regimens in HIV-Infected Antiretroviral Treatment Experienced Children and Adolescents

• Evaluation of suspected adverse drug reaction leading to treatment termination [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Adverse events of Grade 3 or higher severity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Failure to meet PK targets [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

• Virologic failure as defined in protocol [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Changes in co-receptor tropism [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Primary response variables, including pharmacokinetic parameters [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Secondary response variables, including CD4 counts and percent, polymerase genome and envelope sequence, and plasma HIV RNA PCR [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

Highly active antiretroviral therapy (HAART)that includes a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) has become the standard treatment of HIV-infected adults and children. When effective, HAART decreases the viral population, increases the body's immune responses, and leads to decreased disease progression and increased survival. However, several factors including poor adherence, drug toxicities, and drug resistance complicate HIV management and allow for children and adolescents to develop resistance to multiple drug classes, leaving them with very limited therapeutic options. Fortunately, drugs with new mechanisms of action, such as HIV entry inhibitors, demonstrate activity even in people with resistance to the currently available reverse transcriptase and protease inhibitors.

The purpose of this study is to test the effectiveness and safety of Vivriviroc (VCV), an HIV entry inhibitor. Vivriviroc targets the CCR5 chemokine receptor, which HIV uses to bind and enter CD4+ cells.

This study is a two-stage, age-stratified, non-comparative study to explore the safety, tolerability, pharmacokinetic profile and antiviral activity of the investigational CCR5 inhibitor vicriviroc in HIV-infected treatment experienced children and adolescents.

In Step I participants will be screened for the co-receptor CCR5 to assess whether they can enter Step II. Only participants with CCR5-tropic virus are eligible for Step II. Those participants who continue to Step II will be assigned to one of four age-stratifies cohorts which will receive varying forms, either liquid or tablet, of vicriviroc:

Cohort I: 12 years to less than 19 years of age, to receive tablet formulation of VCV

Cohort II: 6 years to less than 12 years of age, to receive tablet formulation of VCV

Cohort III: 6 years to less than 12 years of age, to receive liquid formulation of VCV

Cohort IV: 2 years to less than 6 years of age, to receive liquid formulation of VCV

Dose strengths of 20 mg and 30 mg will be used, or in liquid formulation at a concentration of 1mg/mL.

Step II is composed of Stage I and Stage II. Stage I is a dose ranging study designed to explore how the body responds to different doses of vicriviroc, including safety factors associated with dosage. After optimal dosage information and safety measures have been assessed for the different cohorts in Stage I, Stage II will open. Stage II will evaluate the long term safety, tolerability and effectiveness of vicriviroc.

The study, including Steps I and II will last for approximately 48 weeks. Follow-up for all subjects exposed to vicriviroc will last for 5 years after initial exposure. Visits will be every 3 months for subjects on study provided vicriviroc and every 6 months for subjects who discontinue vicriviroc.