3BNC117 and 10-1074 in ART-treated Individuals

The proposed study is an open label study of the safety and antiretroviral activity of
3BNC117 and 10-1074 in HIV-infected individuals with well-controlled HIV infection on
combination antiretroviral therapy (ART). 3BNC117 and 10-1074 are two broadly neutralizing
antibodies (bNAbs) that target different sites on HIV-1 gp120. Our hypothesis is that the
administration of repeated infusions of 3BNC117 and 10-1074 in the absence of ART will be
safe and well tolerated, will maintain viral suppression in HIV-infected individuals during
analytical treatment interruption (ATI) and will interfere with the maintenance of the HIV-1
reservoir.

Forty eligible participants will be randomized to either Group 1 or Group 2 in a 3:1 ratio:

Group 1 (n=30): participants will discontinue ART 2 days after the first infusion of 3BNC117
and 10-1074, and will receive 6 additional infusions of both antibodies at weeks 2, 4, 8, 12,
16 and 20 (Part A). Participants will remain off ART until week 38, if viral suppression is
maintained (Part B).

Group 2 (n=10): participants will remain on ART and will be administered seven infusions of
3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16 and 20 (Part A). ART will be discontinued at
week 26 until week 38, if viral suppression is maintained (Part B).

After screening, participants will remain on ART and undergo leukapheresis, and will have the
option to undergo LN biopsies 2-4 weeks prior to first 3BNC117 and 10-1074 infusions.

Participants enrolled in group 1 will discontinue their ART 2 days after the first 3BNC117
and 10-1074 infusions. Participants enrolled in group 2 will discontinue their ART at week
26. If the participant's ART regimen includes an NNRTI, the NNRTI will be switched to an
integrase inhibitor-based regimen, 4 weeks prior discontinuing all antiretroviral drugs.

During the ATI periods of the study, ART will be resumed if there is a > 30% decline in CD4+
T cell count or CD4+ T cell count decreases to < 350 cells/μl from baseline (day 0) and these
changes are confirmed during next visit. ART will also be re-initiated if the participant
develops symptoms of severe acute retroviral syndrome or becomes pregnant. In addition, ART
will be resumed according the following virologic parameters:

Part A (wk 0 - wk 26), ART will be resumed if group 1 participants have 2 consecutive plasma
HIV-1 RNA levels > 200 copies/ml.

Part B (wk 26 - wk 38), ART will be resumed if group 1 or group 2 participants have sustained
(> 4 weeks) HIV-1 RNA levels > 1,000 copies/ml.

Part C (wk 38 - wk 48), group 1 and group 2 participants who have not met criteria to
reinitiate ART will be offered to continue off ART with close monitoring. In Part C, ART will
be resumed if the participant has 2 consecutive plasma HIV-1 RNA levels > 1,000 copies/ml.

All participants will be followed for a total of 48 weeks from enrollment (day 0).
Participants will be invited to return for a large blood draw after they reach at least 24
weeks of viral suppression after ART is re-initiated, if this occurs after the active study
follow up period.

Safety assessments will be performed at multiple time points following 3BNC117 and 10-1074
infusions. The effects of 3BNC117 and 10-1074 infusions on the HIV-1 reservoir of
ART-suppressed HIV-infected individuals will be evaluated by several assays. These
evaluations will occur at baseline (day 0) and at week 26.

Inclusion Criteria:

- Male and females, age 18 to 65.

- Confirmed HIV-1 infection.

- On antiretroviral therapy with plasma HIV-1 RNA levels of < 50 copies/ml for at least
12 months, and < 20 copies/ml at screening. Note: a single viral load measurement > 50
but < 500 copies/ml during this time period is allowed.

- Current CD4+ T cell counts > 500 cells/μl and CD4+ T cell count nadir of > 200
cells/μl.

- If on an NNRTI-based regimen, willing to switch to an integrase inhibitor-based
regimen for at least 4 weeks prior to discontinuing ART

- If sexually active male or female, participating in sexual activity that could lead to
pregnancy and of reproductive potential, agrees to follow the contraception
requirements outlined Section 6.12.12 Family Planning Counseling. Participants should
also agree to use a male or female condom while off ART to prevent infecting sexual
partners.

Exclusion Criteria:

- Have a history of AIDS-defining illness within 3 years prior to enrollment.

- History of systemic corticosteroids (long term use), immunosuppressive anti-cancer,
interleukins, systemic interferons, systemic chemotherapy or other medications
considered significant by the trial physician within the last 6 months.

- 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.

- 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.

- History of resistance to 2 or more classes of antiretroviral medication.

- Laboratory abnormalities in the parameters listed below:

- Absolute neutrophil count ≤ 1,000 cells/μl

- Hemoglobin ≤ 10 gm/dL

- Platelet count ≤ 100,000 cells/μl

- Alanine aminotransferase (ALT) ≥ 1.5 x ULN

- Aspartate aminotransferase (AST) ≥ 1.5 x ULN

- Alkaline phosphatase ≥ 1.5 x ULN

- Total bilirubin ≥ 1.5 x ULN

- eGFR < 60 mL/min/1.73m2

- Prothrombin time (PT) > 1.2 x upper limit of normal (ULN). (only if LN biopsies are
performed)

- Partial Thromboplastin Time (PTT) > 1.2 x upper limit of normal (ULN) (only if LN
biopsies are performed)

- Pregnancy or lactation

- Receipt of any therapeutic HIV vaccine or anti-HIV monoclonal antibody therapy in the
past.

- Participants with known hypersensitivity to any constituent of the investigational
products.

- Participation in another clinical study of an investigational product currently or
within past 12 weeks, or expected participation during this study.

- History of intolerance, sensitivity, allergy or anaphylaxis to benzodiazepines or
other narcotics to be used during LN biopsy. (only if LN biopsies are performed)

- Previous adverse reaction or allergy to lidocaine or other amide anesthetics, as well
as benzocaine or other ester type anesthetics. (only if LN biopsies are performed)

- History of underlying medical condition for which antibiotic prophylaxis for invasive
procedures is required (only if LN biopsies are performed)

- Currently taking anticoagulants including but not limited to: heparin (Hep-Lock,
Hep-Pak, Hep-Pak CVC, Heparin Lock Flush), warfarin (Coumadin), tinzaparin (Innohep),
enoxaparin (Lovenox), danaparoid (Orgaran), dalteparin (Fragmin), clopidogrel
(Plavix), dipyridamole (Persantine), fondaparinux (Arixtra), argatroban (Agratroban),
and bivalrudin (Angiomax). Prophylactic aspirin and regular NSAID use permitted. (only
if LN biopsies are performed)