Maraviroc Plus Darunavir/Ritonavir for Treatment-Naïve Patients Infected With R5-tropic HIV-1

Maraviroc Plus Darunavir/Ritonavir Study for Treatment-Naïve Patients Infected With R5-tropic HIV-1 Based on Enhanced Sensitivity Trofile

The objective of this study is to evaluate the safety and efficacy of a novel combination antiretroviral therapy regimen consisting of maraviroc plus darunavir/ritonavir in treatment-naive patients infected with R5-tropic HIV-1. The hypothesis is that in treatment-naive subjects infected with R5-tropic HIV-1, combination antiretroviral therapy with maraviroc plus darunavir/ritonavir is well tolerated and efficacious.

Inclusion Criteria:

• HIV-1 infection, as documented by any licensed HIV test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA any time prior to study entry

• Plasma HIV-1 RNA 5, 000 to 500,000 copies/mL obtained within 90 days prior to study entry

• Exclusive R5 tropism based on enhanced sensitivity Trofile assay done within 90 days prior to entry

• CD4 cell count > 100 cells/mm3 within 90 days prior to study entry

• HIV genotype (for RT and protease) performed at any time before study entry (Subjects with single or combination NNRTI or NRTI RAM(s) at screening are permitted)

• ARV drug-naïve, defined as no previous ARV treatment at any time prior to study entry

• Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry

• Negative result from a hepatitis C antibody test performed within 90 days prior to study entry

• Laboratory values obtained within 30 days prior to study entry:

  • ANC >=750/mm3
  • Hemoglobin >=10 g/dL
  • Platelets >=50,000/mm3
  • AST (SGOT), ALT (SGPT), and alkaline phosphatase <=5 x ULN
  • Calculated creatinine clearance (CrCl) >=30 mL/min, as estimated by the Cockcroft-Gault equation*

• Negative serum or urine pregnancy test within 48 hours prior to study entry for women with reproductive potential

• If participating in sexual activity that could lead to pregnancy, the study subjects with reproductive potential must use one form of contraceptive while receiving protocol-specified medications and for 60 days after stopping the medications.

• Men and women age >=18 years

• Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

• Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry
• Screening HIV genotype obtained any time prior to study entry with any DRV RAM (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V)
• Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy. NOTE: Subjects receiving stable physiologic glucocorticoid doses (defined as prednisone ≤10 mg/day [or equivalent] as a stable or tapering dose) are permitted. Subjects receiving corticosteroids for acute therapy for PCP or asthma exacerbation, or receiving a short course (defined as ≤2 weeks of pharmacologic glucocorticoid therapy) are permitted
• Breast-feeding
• Requirement for any medication that is prohibited with a study medication
• Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion
• Active drug or alcohol use or dependence that could interfere with adherence to study requirements