A Phase 1, Single Dose Study of the Safety and Virologic Effect of an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS) or VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously to HIV-Infected Adults

Study Design:

Open-label, single dose study to examine safety, tolerability, pharmacokinetics and virologic
impact of VRC01LS or VRC07-523LS in HIV-infected viremic adults.

Study Hypotheses:

This is the first study of VRC01LS or VRC07-523LS in HIV-infected viremic adults. The primary
hypothesis is that both VRC01LS and VRC07-523LS will be safe for intravenous administration
to HIV-1-infected adults. The secondary hypothesis is that VRC01LS and VRC07-523LS will be
detectable in human sera with a definable halflife. Part A (VRC01LS) of the study has
completed enrollment.

Product Description:

VRC-HIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB075-00-AB are human MAbs targeted to the CD4+
binding site of HIV-1. Both MAbs are modifications of the VRC01 MAb (which has been shown to
be safe and to have antiviral activity in human studies) with the addition of the LS , a
2-amino acid mutation designed to improve the half-life of the antibody. There are no changes
to the Fab binding sites. These MAbs were developed and manufactured by VRC/NIAID/NIH under
cGMP at the VRC Vaccine Pilot Plant operated under contract by the Vaccine Clinical Materials
Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD. Vials are provided at 100
mg/mL.

Participants:

HIV-1-infected viremic adults; 18-70 years of age.

Study Plan:

This study will assess VRC01LS or VRC07-523LS administered at 40 mg/kg IV in HIV-infected
viremic participants. Participants will enroll in one of two parts: Part A (VRC01LS) and Part
B (VRC07-523LS). Enrollment into Part A (VRC01LS) is complete. Part B enrollment will include
7 participants (up to 10 participants may be enrolled in the event that there are
participants who do not complete the sampling schedule) who will receive VRC07-523LS. Safety
lab samples, HIV viral load, CD4+ count, PK samples, and blood samples for human anti-VRC01LS
antibody (Part A) and human anti-VRC07-523LS antibody (Part B) detection will be drawn at
baseline and intervals throughout the study. Participants will keep a daily diary of
reactogenicity symptoms for 3 days after study product administration and will be queried at
each study visit for adverse events. Participants in Part B will be strongly encouraged to
initiate 3-drug ART (prescribed by their primary HIV clinician; not study-provided) any time
after completing day 14 study evaluations. Results from Part A and Part B may be analyzed,
published, and presented separately since they involve two different MAbs.

VRC 607/A5378 Study Schema:

- Part: A (Enrollment Complete); Participants: 7; Product: VRC01LS; Administration
Schedule (Day 0): 40 mg/kg IV.

- Part: B; Participants: 7; Product: VRC07-523LS; Administration Schedule (Day 0): 40
mg/kg IV.

- Total Participants: 14*

- The expected enrollment is 14 participants (i.e., a minimum of 7 participants
in each part). However, up to 20 participants (i.e., 10 participants in each
part) may be enrolled in the event that there are participants who do not
complete the sampling schedule, if additional PK evaluations are needed, or if
additional participants are needed for safety evaluations.

Study Duration:

Participants will be followed for 48 weeks after study product administration.

- INCLUSION CRITERIA:

A participant must meet all of the following criteria:

1. Able and willing to complete the informed consent process.

2. 18-70 years old

3. Available for clinic visits for 48 weeks after study product administration.

4. HIV-1 infected and clinically stable. [Note: Documented HIV-1 infection by HIV enzyme
immunoassay (EIA) performed by a CLIA certified outside lab within 28 days of
enrollment is acceptable.]

5. At least one plasma viral load >=500 copies/mL within 28 days of enrollment. A plasma
viral load within 28 days and closest to the day of enrollment, that is detectable but
not greater than 100,000 copies/mL. [Note: outside laboratory results will be
acceptable].

6. A CD4+ count >=350 cells/mcL on 2 of 3 consecutive testing occasions (or on 2 of 2
sequential tests) within 28 days prior to enrollment. [Note: outside laboratory
results will be acceptable].

7. In general good health as assessed by a study clinician and under the care of a
primary health care provider for medical management of HIV infection while
participating in the study. Willing to give consent to contact and send laboratory
results to the participant's primary health provider.

8. Willing to have blood samples collected, stored indefinitely, and used for various
research purposes.

9. Able to provide proof of identity to the satisfaction of the study clinician
completing the enrollment process.

10. Screening laboratory values within 28 days prior to enrollment must meet the following
criteria:

- Absolute neutrophil count >=800/mcL

- Platelets >=100,000/mcL

- Hemoglobin >=10.0 g/dL

- Creatinine less than or equal to 1.31 mg/dL

- ALT less than or equal to 2.5 x ULN

- Negative Hepatitis B Surface Antigen (HBsAg)

- Undetectable Hepatitis C Viral Load (HCV RNA)

[Note: Documented negative HBsAg and HCV RNA performed by an outside CLIA certified
lab within 28 days of enrollment are acceptable.]

Female-Specific Criteria:

11. If a woman is sexually active with a male partner and has no history of hysterectomy,
tubal ligation, or menopause, she must agree to use either a prescription birth
control method or a barrier birth control method from the time of study enrollment
until the last study visit, or have a monogamous partner who has had a vasectomy.

12. Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on
day of enrollment for women presumed to be of reproductive potential.

EXCLUSION CRITERIA:

A participant will be excluded if one or more of the following conditions apply:

1. Previous receipt of humanized or human monoclonal antibody whether licensed or
investigational.

2. Prior use of antiretroviral therapy.

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

4. Active drug or alcohol use or dependence in the opinion of the site investigator that
would interfere with adherence to study requirements.

5. Any history of a severe allergic reaction, including generalized urticaria, angioedema
or anaphylaxis prior to enrollment, that has a reasonable risk of recurrence during
the study.

6. Physical finding on examination considered clinically significant.

7. Hypertension that is not well controlled.

8. Weight >115 kg (253 pounds).

9. Breast-feeding.

10. Receipt of any investigational study product within 28 days prior to enrollment.

11. Any other chronic or clinically significant medical condition that in the opinion of
the investigator would jeopardize the safety or rights of the volunteer.