3BNC117 Monoclonal Antibody in HIV-infected Subjects During Treatment Interruption

Inclusion Criteria:

• Age 18 to 65
• HIV-1 infection confirmed by ELISA and immunoblot.
• Plasma HIV-1 RNA < 50 copies/ml for at least 12 months while on combination ART and < 20 copies/ml at the screening visit. [Note: One or two viral blips of < 200 copies/mL prior to enrollment are permitted if preceded and followed by test results showing VL less than or equal to 50 copies/mL on the same ARV regimen.]
• 3BNC117 sensitivity (IC50 < 2 μg/ml) of subject derived HIV-1 virus isolates. These are isolated under protocol MCA-823 by co-culture of subject PBMCs with HIV-uninfected donor PBMCs followed by in vitro neutralization assays as previously described
• Current CD4 cell count > 500 cells/μl and no prior CD4 cell count < 200 cells/μl.
• Willing to interrupt antiretroviral treatment for 12 weeks, or until viral rebound occurs.
• If sexually active male or female, and participating in sexual activity that could lead to pregnancy using an effective method of contraception throughout the study period. Subjects should also agree to use a male or female condom during the time of pausing their HIV medication.
• If on an NNRTI-based regimen willing to a switch for 4 weeks to dolutegravir.

Exclusion Criteria:

• Have a history of AIDS-defining illness within 1 year prior to enrollment
• History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months;
• Chronic hepatitis B or hepatitis C;
• Patient report, or chart history, of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents;
• Patient report, or chart history, of diabetes type 1 or 2 and/or current use of insulin or oral hypoglycemic medications;
• Uncontrolled hypertension, as defined by a systolic blood pressure > 180 and/or diastolic blood pressure > 120, in the presence or absence of anti-hypertensive medications;
• Any other clinically significant acute or chronic medical condition, such as autoimmune diseases, that in the opinion of the investigator would preclude participation;
• Current cigarette use in excess of 1 pack per day;

• Laboratory abnormalities in the parameters listed below:

  • Absolute neutrophil count ≤1,000
  • Hemoglobin ≤ 10 gm/dL
  • Platelet count ≤125,000
  • ALT ≥ 2.0 x ULN
  • AST ≥ 2.0 x ULN
  • Total bilirubin ≥ 1.5 ULN
  • Creatinine ≥ 1.1 x ULN
  • Coagulation parameters ≥ 1.5 x ULN;
• Current antiretroviral regimen includes either maraviroc or enfuvirtide;
• Pregnancy or lactation;
• Any vaccination within 14 days prior to 3BNC117 administration;
• Receipt of any monoclonal antibody therapy of any kind in the past;
• Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
• History of resistance to two or more antiretroviral drug classes