HIV-1 Specific T -Cells (HST-NEETs) for HIV-Infected Individuals

Treatment Description: This is a phase I, multi-site, study of the safety, immunologic and
virologic responses of ex vivo expanded HIV-1 multi-antigen specific T-cell therapy
(HST-NEET) as a therapeutic strategy in HIV-infected individuals suppressed on ART. Patients
will be screened for eligibility in Step 1 and undergo a blood draw of 100-120mL to allow
production of autologous HST-NEETS. Those meeting study eligibility and with successful
production of HST-NEETs will then enter Step 2 where patients have the OPTION of being
enrolled on a separate GWU Protocol 04216 to obtain a pre- and post- HST-NEET treatment
leukapheresis procedure to measure the frequency of HIV-1 infection of resting CD4+ T cells
using the viral outgrowth assay. All participants will then receive (within 30 days of the
leukapheresis procedure if applicable) the same treatment and dose (2x107/m2) of HST-NEETs in
Step 2. For the first 3 recipients, the infusions will occur 4 weeks apart. If no adverse
reactions occur that are attributable to the HST-NEETs, the recipients thereafter will
receive the two infusions separated by 2 weeks.

Sample Size and Study Duration: Up to 12 HIV-infected individuals followed for 48 weeks.

Accrual Objective: The total sample size is 12 participants. Participants will be followed
for 48 weeks. Because the focus of the study is on safety and potential adverse events are
most likely to occur within 28 days of administration, accrual will be staggered such that
enrollment and treatment administration will include a maximum of 1 participant per week.
Participants who do not receive study treatment will be replaced. In addition, any
participant who is not administered the full study treatment infusion, or discontinues the
study prior to day 28 without having met the primary safety endpoint will be replaced until
the target enrollment of participants is met.

Inclusion Criteria:

Recipient Inclusion Criteria for cell procurement and cell infusion:

- ≥ 18 years and < 65 years of age

- Confirmation of HIV-1 infection

- any licensed ELISA test kit which is confirmed by Western blot or Multispot
HIV-1/HIV-2 assay prior to screening. HIV culture, HIV antigen, plasma HIV RNA, or a
second antibody test by a method other than ELISA is acceptable as an alternative
confirmatory test.

- On potent antiretroviral therapy, defined as at least 2 nucleoside/nucleotide reverse
transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor,
integrase inhibitor, or a protease inhibitor without interruption (Interruption is
defined as missing doses by self report for no more than two (2) consecutive days or
more than four (4) cumulative days) in the 12 weeks prior to cell procurement for HST
NEETs manufacturing. Other potent fully suppressive antiretroviral combinations will
be considered on a case- by-case basis. Prior changes in or elimination of medications
for easier dosing schedule, intolerance, toxicity, or other reasons are permitted if
an alternative suppressive regimen was maintained under the compliance criteria above.

- Stable ART regimen for minimum of 12 weeks with no detectable HIV RNA concentrations
as defined above. Participants may have had one or more changes in their ART regimen
during the 12 week for tolerance, or dosing simplification.

- Ability and willingness of participant to continue and be compliant with cART
throughout the study.

- Plasma HIV-1 RNA below detectable limit by conventional CLIA approved assays (<50
copies/mL) for ≥ 1 year. A single unconfirmed plasma HIV RNA > limit of detection but
< 1000 c/mL is allowed within the 12 months prior to screening/cell donation but none
in the preceding 6 months, is permitted provided that a repeat RNA was < 20.

- Plasma HIV-1 RNA < 50 copies/mL at screening.

- CD4+ cell count > 350 cells/mm3 at screening.

- Karnofsky score of ≥ 50%

- No active HCV infection (measureable HCV RNA) within 90 days of cell procurement.

- No active HBV infection (measureable HBV DNA or HBVsAg+) within 90 days of cell
procurement.

- All female participants participating in sexual activity that could lead to pregnancy
must agree to use at least two of the following reliable methods of birth control (at
least one of which is a barrier method) for at least 21 days prior to study entry,
continuing and until 12 weeks after the last dose of the study product: condoms (male
or female) with or without a spermicidal agent, diaphragm or cervical cap with
spermicide, Intrauterine Device, hormone-based contraceptive, tubal ligation,
NuvaRing.

- All male participants participating in sexual activity that could lead to pregnancy
must agree to use condoms for at least 21 days prior to study entry, continuing and
until 12 weeks after the last dose of the study product.

- Ability and willingness of subject to give written informed consent.

- Ability and willingness to provide adequate locator information and contact
information for at least 2 adults who can reach the participant within 24 hours

- Ability and willingness to communicate effectively with study personnel; considered
reliable, willing, and cooperative in terms of compliance with the Protocol
requirements.

- Adequate vascular access (peripheral and central) for HST-NEET infusion.

Exclusion Criteria:

- Prior use of any HIV immunotherapy or vaccine within 12 months prior to Screening.

- Use of any of the following within 90 days prior to entry: immunomodulatory, cytokine,
or growth stimulating factors such as systemic corticosteroids, cyclosporine,
methotrexate, azathioprine, anti-CD25 antibody, IFN, interleukin-2 (IL-2), Coumadin,
warfarin, or other Coumadin derivative anticoagulants.

- Patients on a CCR5 inhibitor or an entry inhibitor are not eligible for participation
in the study

- Received any infusion blood product, immune globulin, or hematopoietic growth factors
within 90 days prior to study entry.

- History of malignancy, immunodeficiency other than HIV, or any other condition that
would make the subject unsuitable for the study in the opinion of the performance site
PIs.

- Any active malignancy that may require chemotherapy or radiation therapy.

- Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza,
pneumococcal polysaccharide) within 4 weeks prior to study entry.

- Inability to comply with study requirements, which could impact study integrity and/or
safety.