3BNC117 Monoclonal Antibody in HIV-infected Subjects During Treatment Interruption
Condition: HIV-1 Infection
Intervention: 3BNC117; ART Interruption
Intervention description: 3BNC117 infusions; Antiretroviral therapy will be discontinued 2 days after the first 3BNC117 infusion (day 2) and resumed at week 12.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV; 3BNC117; Broadly neutralizing antibody

Summary:

      This study evaluates the effects of two infusions of 3BNC117 in preventing or delaying
      rebound of viral load during a brief treatment interruption of standard ART and its safety
      during a brief analytical interruption of antiretroviral therapy.
    

Eligibility criteria:

        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