A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial of a Novel CCR5 Antagonist, UK-427,857, in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced, Non CCR5-Tropic HIV-1 Infected Subjects

Maraviroc (UK-427,857), a selective and reversible CCR5 co-receptor antagonist, has been
shown to be active in vitro against a wide range of clinical isolates (including those
resistant to existing classes). In HIV-1 infected patients in the United States, maraviroc
(UK-427,857) is approved for use as part of combination antiretroviral treatment in
treatment-experienced and treatment-naive adult subjects. At least 50% of
treatment-experienced patients are infected with R5-tropic HIV-1 exclusively. However, even
in patients infected with a dual tropic (R5 + X4) phenotype, a large proportion of the virus
population still uses CCR5 exclusively. Thus, the purpose of this study is to evaluate the
antiretroviral activity, and safety, of maraviroc (UK-427,857) (in combination with other
agents) in HIV infected, treatment experienced patients who are failing their current
antiretroviral regimen and not infected with R5-tropic virus exclusively. This study will
involve more than 200 centers globally to achieve a total randomized subject population of
192 subjects. Patients will be randomly (1:1:1) assigned to one of three groups: Optimized
Background Therapy [OBT (3-6 drugs based on treatment history and resistance testing)] +
maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken
twice daily, or OBT alone. Randomization was stratified by Enfuvirtide use in OBT (yes/no)
and Screening HIV-1 RNA level (viral load) (<100,000/≥ 100, 000 copies per milliliter [copies
per mL]). The study will enroll over approximately a 9 month period with 48 weeks of
treatment. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20,
24, 32, 40 and 48. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16,
20, 24, 32, 40, and 48. Additionally, blood samples will be drawn twice, at least 30 minutes
apart, at weeks 2 and 24 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this
clinical study a blood sample will also be taken for non-anonymized pharmacogenetic analysis.
Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24 and 48.