HIV Attachment Inhibitor to Treat Human Immunodeficiency Virus 1 (HIV-1) Infections

• Proportion of subjects with plasma HIV-1 ribonucleic acid (RNA) < 50 c/mL [ Time Frame: At Week 24 ] [ Designated as safety issue: No ]
• Frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]

• Changes from monotherapy baseline (Monotherapy Day 1) in log10 HIV ribonucleic acid (RNA) by study day during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ] [ Designated as safety issue: No ]
  Monotherapy Substudy
• Maximum decrease from monotherapy baseline in log10 plasma HIV-1 RNA during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ] [ Designated as safety issue: No ]
  Monotherapy Substudy
• Proportion of subjects with plasma HIV-1 RNA < 50 c/mL at baseline (Combination Therapy Day 1) [ Time Frame: Baseline and at Monotherapy Day 7 ] [ Designated as safety issue: No ]
  Monotherapy Substudy
• Frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) during monotherapy [ Time Frame: At Monotherapy Day 7 ] [ Designated as safety issue: Yes ]
  Monotherapy Substudy
• Changes from monotherapy baseline in CD4+ and CD8+ T-cell counts and percents by study day during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ] [ Designated as safety issue: No ]
  Monotherapy Substudy
• Proportion of subjects with plasma HIV-1 RNA < 50 c/mL [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  Primary Study
• Proportion of subjects with plasma HIV-1 RNA < 50 c/mL [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  Primary Study
• Frequency of SAEs and discontinuations due to AEs [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  Primary Study
• Frequency of SAEs and discontinuations due to AEs [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
  Primary Study
• Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  Primary Study
• Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  Primary Study
• Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
  Primary Study
• Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  Primary Study
• Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  Primary Study
• Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  Primary Study

The purpose of this study is to assess the safety, efficacy, tolerability and pharmacokinetics of four doses of BMS-663068 with Raltegravir (RAL) + Tenofovir Disoproxil Fumarate (TDF). At least 1 dose of BMS-663068 can be identified which is safe, well tolerated, and efficacious when combined with RAL + TDF for treatment-experienced HIV-1 infected subjects.

Masking: Double-blind for BMS-6630368 treatment groups until the Week 24 Primary Endpoint analysis, then open label. The reference groups is all open-label.

Arms: 5 (4 BMS-663068 treatment groups and 1 reference group)

Intervention Model: Parallel (with unblinding after the Week 24 primary endpoint analysis)

• Drug: BMS-663068
  Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose
• Drug: BMS-663068
  Tablets, Oral, 800 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose
• Drug: BMS-663068
  Tablets, Oral, 600 mg, once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose
• Drug: BMS-663068
  Tablets, Oral, 1200 mg, once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose
• Drug: Raltegravir
  Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose
  Other Name: Isentress
• Drug: Raltegravir
  Tablets, Oral, 400 mg, twice daily (BID), 96 weeks
  Other Name: Isentress
• Drug: Tenofovir
  Tablets, Oral, 300 mg, Once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose
  Other Name: Viread
• Drug: Tenofovir
  Tablets, Oral, 300 mg, Once daily (QD), 96 weeks
  Other Name: Viread
• Drug: Ritonavir
  Tablets, Oral, 100 mg, Once daily, 96 weeks
  Other Name: Norvir
• Drug: Atazanavir
  Capsules, Oral, 300 mg, Once daily, 96 weeks
  Other Name: Reyataz

• Experimental: Arm A: BMS-663068 + Raltegravir + Tenofovir
  Treatment Group 1
  Interventions:

  • Drug: BMS-663068
  • Drug: Raltegravir
  • Drug: Tenofovir
• Experimental: Arm B: BMS-663068 + Raltegravir + Tenofovir
  Treatment Group 2
  Interventions:

  • Drug: BMS-663068
  • Drug: Raltegravir
  • Drug: Tenofovir
• Experimental: Arm C: BMS-663068 + Raltegravir + Tenofovir
  Treatment Group 3
  Interventions:

  • Drug: BMS-663068
  • Drug: Raltegravir
  • Drug: Tenofovir
• Experimental: Arm D: BMS-663068 + Raltegravir + Tenofovir
  Treatment Group 4
  Interventions:

  • Drug: BMS-663068
  • Drug: Raltegravir
  • Drug: Tenofovir
• Active Comparator: Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir
  Treatment Group 1 (reference arm)
  Interventions:

  • Drug: Raltegravir
  • Drug: Tenofovir
  • Drug: Ritonavir
  • Drug: Atazanavir

Inclusion Criteria:

• Plasma HIV-1 RNA ≥ 1000 copies/ml at Screening
• Treatment experience with antiretroviral therapies (excluding integrase inhibitors)
• Screening PhenoSense® Entry indicating BMS-626529 inhibitory concentration (IC)50 < 0.1 μM
• Cluster of differentiation (CD)4+ T-cell count > 50 cells/mm3

Exclusion Criteria:

• History (or evidence at Screening) of genotypic resistance to any component of the study regimen [ Tenofovir Disoproxil Fumarate (TDF), Atazanavir (ATV), Raltegravir (RAL)]
• Certain laboratory and electrocardiogram (ECG) values