Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK),
and antiviral activity of a human monoclonal antibody, VRC-HIVMAB060-00-AB (known as VRC01),
in HIV-infected adults whose HIV is well-controlled with antiretroviral therapy (ART). The
study will examine whether VRC01 delays or prevents the return of HIV viremia in
participants who are undergoing a brief analytical treatment interruption (ATI).

The study will enroll HIV-infected participants 18 years and older who are on ART. (ART will
not be provided by the study). At a pre-entry study visit, participants will undergo blood
collection, a leukapheresis procedure, and a rectal biopsy. The study will last about 21
weeks and proceed in two stages: Step 1 (approximately 9 weeks) and Step 2 (approximately 12
weeks).

During Step 1, participants will receive three doses of VRC01 via intravenous (IV) infusion.
The first dose of VRC01 will be given on day 0. Seven days after receiving this first dose
of VRC01, participants will discontinue ART. Participants will receive the second and third
doses of VRC01 at days 21 and 42, respectively. For 7 days after each VRC01 IV infusion,
participants will monitor and record their temperature and any symptoms. In addition to the
3 injection study visits, participants will attend weekly visits from day 7 through
approximately day 63 (week 9).

Participants will enter Step 2 of the study and resume ART when they have a confirmed return
of HIV-1 viremia or a confirmed CD4+ T-cell count of less than 350 cells/μL.

Step 2 study visits will occur on the day ART is resumed (Step 2, week 1) and every four
weeks thereafter (approximately at Step 2, weeks 4, 8, and 12) until a participant's HIV
viral load decreases to less than 50 copies/mL.

Throughout the study, visits will include clinical assessments and blood collection. Some
blood will be stored for future testing. Some study visits will include the collection of
oral, rectal, and (for women) cervical secretion samples. On day 63, participants will
undergo another leukapheresis procedure and a rectal biopsy.

Step 1 Inclusion Criteria:

- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or
chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and
confirmed by a licensed Western blot or a second antibody test by a method other than
the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load
(VL). More information on this criterion can be found in the protocol.

- Ability and willingness of participant or legal representative to provide informed
consent

- Men and women greater than or equal to 18 years old

- Clinically stable on their first or second ART regimen that includes a boosted
protease inhibitor or an integrase inhibitor. The current regimen should be stable
for 8 weeks at the time of entry. Changes while the patient HIV viral load is
undetectable does not count toward the number of ART regimens used, (for example an
individual switching from a non-nucleoside reverse transcriptase inhibitor
(NNRTI)-based regimen to an integrase inhibitor based regimen while the HIV viral
load is undetectable will still be in their first regimen).

- HIV-1 RNA that is less than 50 copies/mL using a Food and Drug Administration
(FDA)-approved assay performed by any laboratory that has a Clinical Laboratory
Improvement Amendments (CLIA) certification or its equivalent within 45 days prior to
study entry

- HIV-1 RNA less than 50 copies/mL using a FDA-approved assay for at least 24 weeks
prior to study entry performed by any laboratory that has a CLIA certification or its
equivalent. More information on this criterion can be found in the protocol.

- Screening CD4+ T-cell count greater than or equal to 450 cells/μL within 45 days
prior to study entry

- Nadir CD4+ T-cell count greater than 200 cells/μL

- Willingness to have blood samples collected, stored indefinitely, and used for
study-related research purposes

- The following laboratory values obtained within 45 days prior to enrollment:

- Absolute neutrophil count (ANC) greater than or equal to 1000 cells/mm^3

- Hemoglobin greater than or equal to 12.0 g/dL for men and greater than or equal
to 11.0 g/dL for women

- Platelet count greater than or equal to 100,000/mm^3

- Creatinine clearance greater than or equal to 60 mL/min estimated by the
Cockcroft-Gault equation. More information on this criterion can be found in the
protocol.

- Alanine aminotransferase (ALT) less than or equal to 2.0 times the upper limit
of normal (ULN)

- At least eight participants will have availability of plasma or serum specimen before
the initiation of ART either in the Center for AIDS Research (CFAR) repository of the
University of Pennsylvania, University of Alabama, or in the AIDS Clinical Trials
Group (ACTG) central repository

- For females of reproductive potential (i.e., women who have not been post-menopausal
for at least 24 consecutive months; who have had menses within the preceding 24
months; or women who have not undergone surgical sterilization, specifically
hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy), negative
urine pregnancy test (with a sensitivity of 15 to 25 mIU/mL) within 48 hours prior to
screening and entry. More information on this criterion can be found in the protocol.

- Contraceptive methods will be required for female participants of reproductive
potential. Female participants of reproductive potential and their male partners MUST
appropriately use at least two contraceptives, with one method being highly effective
and the other method being either highly effective or less effective. More
information on this criterion, including a list of acceptable contraceptive options,
can be found in the protocol.

- Contraceptive methods will be required for female partners of reproductive potential
of male study participants on study drug. Female partners of reproductive potential
of male study participants and/or their male partners MUST appropriately use at least
two contraceptives, with one method being highly effective and the other method being
either highly effective or less effective. More information on this criterion,
including a list of acceptable contraceptive options, can be found in the protocol.

- Negative hepatitis B surface antigen (HBsAg) result obtained within 6 months prior to
study entry

- Hepatitis C virus (HCV) antibody negative result within 6 months prior to entry, or
if the HCV antibody result is positive, a negative HCV RNA obtained within 6 months
prior to study entry

- Adequate venous access in at least one arm

Step 2 Inclusion Criteria:

- Entry into Step 1 of this study (A5340)

- Receipt of at least one dose or partial dose of VRC01 in Step 1

- Reinitiating ART for protocol or non-protocol-defined reasons. More information on
this criterion can be found in the protocol.

Step 1 Exclusion Criteria:

- Previous receipt of humanized or human monoclonal antibody whether licensed or
investigational

- Weight greater than 115 kg or less than 53 kg

- History of an AIDS-defining illness

- Ongoing AIDS-related opportunistic infection (including oral thrush)

- History of a severe allergic reaction with generalized urticaria, angioedema, or
anaphylaxis in the 2 years prior to enrollment

- Currently breastfeeding

- Receipt of other investigational study agent within 30 days prior to enrollment

- Treatment with systemic glucocorticoids (e.g., prednisone or other glucocorticoid) or
other immunomodulators (other than nonsteroidal anti-inflammatory drugs [NSAIDs])
within 30 days prior to enrollment

- Any other chronic or clinically significant medical condition that in the opinion of
investigator would jeopardize the safety or rights of the participant, including, but
not limited to diabetes mellitus type I, OR clinically significant forms of drug or
alcohol abuse, severe asthma, autoimmune disease, uncontrolled hypertension, liver
disease, psychiatric disorders, heart disease, or cancer

- Treatment during acute infection (i.e., treatment within 6 months of acute infection)

- Current use of a NNRTI

Step 2 Exclusion Criteria:

- Non-participation in Step 1