A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117

In preclinical studies carried out in humanized mice and non-human primates, 3BNC117 alone
or in combination with other neutralizing antibodies led to protection from HIV-1 or SHIV
infection and also to sustained suppression of HIV-1 plasma viremia. The aims of this
protocol are to evaluate the safety, tolerability and pharmacokinetics profile of 3BNC117 in
both HIV-infected and HIV-uninfected subjects,and its antiretroviral activity in
HIV-infected subjects.

Inclusion Criteria:

- Group 1 (HIV-uninfected):

- Adult males and females, age 18 to 65

- Amenable to HIV risk reduction counseling and agrees to maintaining behavior
consistent with low risk of HIV exposure;

- If a sexually active male or female, participating in sexual activity that could
lead to pregnancy, agrees to use an effective method of contraception throughout
the study.

- Groups 2-5 (HIV-infected):

- Age 18 to 65

- HIV infection confirmed by ELISA and immunoblot

- Groups 2A-D - on ART with HIV-1 plasma RNA levels below 100,000 copies/ml, or
off ART for at least 8 weeks with HIV-1 plasma RNA level between 2,000-100,000
copies/ml by standard assays on 2 occasions at least 1 week apart;

- Group 2E - Untreated HIV-infected (not on ART for at least 8 weeks): HIV-1 RNA
plasma levels between 2,000 - 100,000 copies/ml;

- Group 3 - Untreated HIV controllers (not on ART for at least 8 weeks): HIV-1 RNA
plasma level of < 2,000 copies/ml by standard assays, on 2 occasions, at least 1
week apart, and ART-naive.

- Group 4 - ART treated with HIV-1 RNA plasma level of > 20 copies/ml by standard
assays on 2 occasions, at least 1 week apart, while on combination
antiretroviral therapy;

- Groups 5A and 5B - ART treated with HIV-1 RNA plasma level of < 20 copies/ml by
standard assays on 2 occasions, at least 1 week apart, while on combination
antiretroviral therapy;

- Current CD4 cell count > 300 cells/µl

- If sexually active male and female, participating in sexual activity that could
lead to pregnancy, agrees to use an effective method of contraception throughout
the study.

Exclusion criteria:

- Group 1 (HIV-uninfected):

- Confirmed HIV-1 or HIV-2 infection;

- 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;

- Any clinically significant acute or chronic medical condition that in the
opinion of the investigator would preclude participation;

- Within the 12 months prior to enrollment, the volunteer has a history of
sexually transmitted disease;

- Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies);

- Laboratory abnormalities in the parameters listed below:

- Absolute neutrophil count ≤ 2,000

- Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male

- Platelet count ≤ 140,000

- ALT ≥ 1.25 x ULN

- AST ≥ 1.25 x ULN

- Total bilirubin ≥ 1.1 ULN

- Creatinine ≥ 1.1 x ULN

- Coagulation parameters (PT, PTT, INR) ≥ 1.1 x ULN

- Pregnancy or breastfeeding;

- Any vaccination within 14 days prior to 3BNC117 administration;

- Receipt of any experimental HIV vaccine in the past or 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.

- Groups 2-5 (HIV-infected):

- History of AIDS-defining illness

- History of systemic corticosteroids, immunosuppressive anti-cancer, or other
medications considered significant by the trial physician within the last 6
months;

- Any clinically significant acute or chronic medical condition, other than HIV
infection, that in the opinion of the investigator would preclude participation;

- Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies);

- Laboratory abnormalities in the parameters listed below:

- Absolute neutrophil count ≤ 1,300

- Hemoglobin ≤ 10 gm/dL

- Platelet count ≤ 125,000

- ALT ≥ 2.0 x ULN

- AST ≥ 2.0 x ULN

- Total bilirubin ≥ 1.1 ULN

- Creatinine ≥ 1.1 x ULN

- Coagulation parameters ≥ 1.1 x ULN;

- Current antiretroviral regimen includes either maraviroc or enfuvirtide;

- Pregnancy or breastfeeding;

- Any vaccination within 14 days prior to 3BNC117 administration;

- Receipt of any experimental HIV vaccine or 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.