Adoptive Transfer of Haploidentical Natural Killer Cells and IL-2

Potential subjects will be screened to determine eligibility. Immediately after consent and
screening, an HLA-haploidentical donor will be identified and will complete eligibility
screen and consent. At Day -7 the subject will undergo an inguinal lymph node biopsy and
colonoscopy to obtain ileal and rectal biopsies. Blood samples will be obtained to measure
chimerisms, plasma HIV RNA, and inflammatory cytokines. PBMCs will be obtained to sort into
CD4 subsets and measure frequencies of HIV RNA and DNA. On Day -1, the donor will undergo
apheresis and donor cells will be obtained and incubated overnight with IL-2. On Day 0
subjects will start aspirin and be infused with IL-2 activated NK cells. Subjects will
receive 6 million units of IL-2 just after the infusion and they will be monitored on the
Phase 1 Unit for 24 hours. Plasma will be obtained at 2 hrs, 4 hrs and the following morning
and stored for measures of inflammatory markers. The subject will return to the outpatient
clinic on days 2, 4, 6, 8, and 10 after the infusion for administration of 6 million units of
IL-2 and to obtain plasma and PBMC for measures of inflammatory markers and changes to the
virus reservoir. On day 14 the subject will stop taking ASA and blood will be obtained to
measure frequencies of HIV RNA and DNA. On day 21 will have a lymph node biopsy and
colonoscopy to obtain ileal and rectal tissues. The patient will then be followed until day
100 post NK cell infusion. Subjects will return every 2 weeks for a toxicity assessment,
blood draws, and viral level testing. Study participation will end after day 100.

Inclusion Criteria:

- ¥ Age-18-65

- Stable ART for at least 12 months.

- Screening plasma HIV RNA levels below level of quantification (<40 to <50 copies
RNA/mL depending on the assay) for ≥ 6 months (a total of 3 measurements above
the level of detection but < 500 copies/ml will be allowed if each detectable
measure is separated by at least 1 year)

- Screening CD4 count ≥500 cells/µl

- Laboratory tests (CBCD, CMP, Mg, Phosphorus, PT/PTT, TSH/T4,) performed within 14
days of study enrollment. All laboratory results (unless otherwise specified)
must be Grade 1 or normal based on the DAIDS Adverse Event Grading Scale
(Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric
Adverse Events v2.0)

- Adequate kidney function defined by estimated GFR (CrCl) > 60 ml/min or
ml/min/1.73 m2 (≤ grade 2 per DAIDS) and creatinine ≤ 1.5 x ULN

- Adequate pulmonary function without any clinical signs or symptoms of severe
pulmonary dysfunction. PFT testing must show FEV1 and DLCOcorr > 50% of predicted
if subjects have symptomatic or prior known impairment.

- Transthoracic echocardiogram with PA pressures in the range of 18-26 mmHg

- Ability to be off prednisone and other immunosuppressive drugs for at least 14
days before infusion of cells

- Women of child bearing potential and men with partners of child bearing potential
must agree to use effective contraception during therapy and for 4 months after
completion of therapy

- Voluntary written consent provided by the subject

Exclusion Criteria:

- Any condition that precludes lymph node biopsy or colonoscopy with biopsy

- Active infection other than HIV currently requiring systemic antimicrobial
therapy

- History of deep vein thrombosis

- Active significant, tissue invasive fungal infection requiring systemic
antifungal therapy (dermatologic conditions requiring only topical therapy are
allowed).

- Chronic active hepatitis B or C (defined as antibody positive and DNA+ or
HepBsAG+).

- Breastfeeding

- Intended modification of antiretroviral therapy in the next 24 weeks

- NYHA (New York Heart Association) Class III or IV heart failure, uncontrollable
supraventricular arrhythmias, any history of a ventricular arrhythmia, or other
clinical signs of severe cardiac dysfunction

- Symptomatic congestive heart failure, unstable angina pectoris, or Myocardial
infarction within 6 months prior to screening

- Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc
interval greater than 500 milliseconds)

- On-going chronic systemic corticosteroid use or other immunosuppressive therapy
(a history of mild asthma not requiring therapy is eligible and inhaled
corticosteroids is allowed. Topical steroids are allowed.)

- Psychiatric illness/social situations that would limit compliance with study
requirements

- Previous diagnosis of an autoimmune disease (e.g. rheumatoid arthritis, lupus,
inflammatory bowel disease, multiple sclerosis, vasculitis)

- Use of any anticoagulants within the previous 4 weeks.

- Other illness that in the opinion of the investigator would exclude the patient
from participating in this study