3BNC117-LS First-in-Human Phase 1 Study

Inclusion Criteria:

Groups 1A-1F (HIV-uninfected):

1. Males and females, age 18 to 65
2. Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.

3. If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.

   • Female study participants of reproductive potential are defined as pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.

Groups 2B-2D (HIV-infected):

1. Males and females, age 18 to 65.
2. HIV-1 infection confirmed by two laboratory assays.
3. HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml by standard assays (ART-naïve or off ART due to intolerance or by choice), or on ART with HIV-1 plasma RNA levels < 20 copies/ml. HIV-1 RNA levels should be measured on 2 occasions, at least 1 week apart. At least one measurement must be performed within 49 days prior to enrollment (day 0). Group 2D will only enroll HIV-infected individuals on ART.
4. Current CD4+ T cell count > 300 cells/μl.
5. If sexually active male or female, and participating in sexual activity that could lead to pregnancy or transmission of HIV, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.

Exclusion Criteria:

Groups 1A-1F (HIV-uninfected):

1. Confirmed HIV-1 or HIV-2 infection.
2. History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
3. Any clinically significant acute or chronic medical condition (such as autoimmune diseases) that in the opinion of the investigator would preclude participation.
4. Within the 12 months prior to enrollment, the participant has a history of sexually transmitted infection.
5. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.

6. Laboratory abnormalities in the parameters listed:

   • Absolute neutrophil count ≤ 1,500 cells/µL;
   • Hemoglobin ≤ 11 gm/dL if female; ≤ 12.5 gm/dL if male;
   • Platelet count ≤ 125,000 cells/µL;
   • Alanine transaminase (ALT) ≥ 1.25 x ULN;
   • Aspartate transaminase (AST) ≥ 1.25 x ULN;
   • Alkaline phosphatase ≥ 1.5 x ULN;
   • Total bilirubin > 1 x ULN;
   • Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2.
7. Pregnancy or lactation.
8. Any vaccination within 14 days prior to 3BNC117-LS infusion.
9. Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
10. History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
11. Individuals with known hypersensitivity to any constituent of the investigational product.
12. Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.

Groups 2B-2D (HIV-infected):

1. Have a history of AIDS-defining illness within 3 years prior to enrollment.
2. History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
3. Any clinically significant acute or chronic medical condition (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
4. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.

5. Laboratory abnormalities in the parameters listed below:

   • Absolute neutrophil count ≤ 1,000 cells/μl;
   • Hemoglobin ≤ 10 gm/dL;
   • Platelet count ≤ 100,000 cells/μl;
   • ALT ≥ 1.5 x ULN;
   • AST ≥ 1.5 x ULN;
   • Alkaline phosphatase ≥ 1.5 x ULN;
   • Total bilirubin > 1 x ULN;
   • eGFR < 60 mL/min/1.73m2.
6. Pregnancy or lactation.
7. Any vaccination within 14 days prior to 3BNC117-LS infusion.
8. Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
9. History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
10. Individuals with known hypersensitivity to any constituent of the investigational product.
11. Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.