INCLUSION CRITERIA RECIPIENT:
Under this protocol, cell recipients must fulfill all of the following characteristics and conditions:
Greater than or equal to 18 years old
Ability to sign informed consent
For women of child-bearing potential, negative result on a serum or urine pregnancy test; in addition, men and women of childbearing potential must agree to practice abstinence or use two methods of birth control / contraception (condoms, diaphragm or cervical cap with spermicide, IUD, or hormonal-based contraception) for at least 4 weeks after each cell infusion
Willingness to comply with study requirements and procedures including storage of blood for possible future use to study HIV/AIDS, related diseases, or the immune system
Willingness to permit HLA testing
HLA-B*57 positive
Hematocrit greater than or equal to 27 percent, platelets greater than or equal to 25,000/mm (3)
No significant underlying cardiac, renal, or hepatic disease (Creatinine less than 2.0 mg/dL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 150 U/mL)
HIV infection must be confirmed by ELISA and western blot if not previously documented, and patients must be under the care of a primary care physician.
Viral load greater than 10,000 copies/mL on combination antiretroviral therapy, to include at least 3 drugs, one of which is a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor. Patients not on combination antiretroviral therapy will be eligible, but must be willing to resume combination antiretroviral therapy and to have had a viral load greater than 10,000 copies/mL after at least 2 weeks of therapy.
Failure of at least two previous combination regimens, one containing an NNRTI and one containing a protease inhibitor. Failure will be defined as an HIV viral load greater than 400 copies/mL while taking a given regimen. Patients who have failed a protease inhibitor-containing regimen and are intolerant of both efavirenz and nevirapine will be permitted to enroll.
Recipient must be taking appropriate prophylaxis for opportunistic infections, as per Public Health Service (PHS) guidelines, unless there is intolerance to available medications.
Screening CD4+ cell count less than or equal to 200 cells/mm(3) obtained within 6 weeks prior to study entry.
EXCLUSION CRITERIA FOR RECIPIENT:
An individual will be ineligible to receive cells if one or more of the following conditions are present:
Discordance with donor on antibody status of EBV, CMV, or HHV-8 if donor is antibody positive for EBV, CMV, or HHV-8.
Malignancy requiring systemic therapy, or a history of malignancy that required myelotoxic chemotherapy.
Active untreated opportunistic infection that requires systemic therapy. Patients with opportunistic infections who have received greater than 2 weeks of therapy will be eligible.
Is pregnant or breast feeding.
Severe psychiatric disorder that would interfere with adherence to protocol requirements. Individuals who have a stable psychiatric condition may be eligible.
Current use or a history of treatment with investigational agent(s) within 3 months of protocol enrollment. ARVs obtained through expanded access programs are permitted.
Current use or a history of treatment with a systemic corticosteroid, immunosuppressive, or cytotoxic agent within 30 days of protocol enrollment.
Any other medical condition for which the investigator believes cell transfer may be contraindicated.
Ever been diagnosed with autoimmune vasculitis.
Discordance with donor on subtype of HLA-B*57
INCLUSION CRITERIA DONOR:
Donor eligibility criteria as specified by the FDA will be followed, except for HIV testing. All donors will be HIV positive as per protocol and as described in the IND application. Under this protocol, cell donors must fulfill all of the following characteristics and conditions:
Greater than or equal to 18 years old.
Ability to sign informed consent.
For women of child-bearing potential, negative result on a serum or urine pregnancy test.
Willingness to comply with study requirements and procedures including storage of blood for possible future use to study HIV/AIDS, related diseases, or the immune system.
Willingness to permit HLA testing.
HLA-B*57 positive.
Hematocrit greater than or equal to 27 percent, platelets greater than or equal to 100,000/mm(3), white blood cells greater than or equal to 3.0 times 10(9)/L.
No underlying cardiac, pulmonary, renal, or hepatic disease that would preclude patient from undergoing apheresis.
HIV infection must be confirmed by ELISA and western blot if not previously on record, and patients must be under the care of a primary care physician.
CD4+ cell count greater than or equal to 400 cells/mm(3) and HIV viral load less than 50 copies/mL, with no recorded HIV viral load greater than 1,000 copies/mL.
HIV infection for greater than or equal to 7 years.
Minimum wt of 110 lbs
From 1980 through 1996, did not spend time that adds up to three (3) months or more in the United Kingdom.
From 1980 to the present, did not spend time that adds up to five (5) years or more in Europe.
From 1980 to the present, did not receive a blood transfusion in the United Kingdom.
EXCLUSION CRITERIA FOR DONOR:
An individual will be ineligible to donate cells if one or more of the following conditions are present:
Ever having been diagnosed with any AIDS-defining illnesses
Ever being on antiretroviral therapy other than one or two nucleotide reverse transcriptase inhibitor (NRTI) drugs; no NRTI therapy during the previous year
Positive results on screening test for any of the following tests: HCV enzyme immunoassay (EIA) repeat reactive/ recombinant immunoblot (RIBA) confirmed, HEP C NAT, anti-HTLV-I/II antibodies, HBsAg, HBV PCR, RPR (with positive confirmatory treponemal-based assay), or West Nile Virus NAT
Is pregnant or breast feeding
HLA homozygous donor who is haplo-identical to recipient
History of malignancy other than basal cell carcinoma of the skin, or in situ carcinoma of cervix or colon
ALT or AST greater than 2 times the upper limit of normal
Veins too difficult to access to insert the needle
Been diagnosed with malaria
Been diagnosed with Chagas' disease
Been diagnosed with babesiosis
Received a dura mater (or brain covering) graft
Been diagnosed with any neurological disease
Relative had Creutzfeldt-Jakob disease
Had a transplant or other medical procedure that involved being exposed to live cells, tissues, or organs from an animal
Had a sexual partner or a member of the household have a transplant or other medical procedure that involved being exposed to live cells, tissues, or organs from an animal
Severe psychiatric disorder that would interfere with adherence to protocol requirements. Individuals who have a stable psychiatric condition may be eligible.
Current use or a history of treatment with investigational agent(s) within 3 months of protocol enrollment.
Current use or a history of treatment with a systemic corticosteroid, immunosuppressive, or cytotoxic agent within 30 days of protocol enrollment.
Any other medical condition for which the investigator believes apheresis may be contraindicated.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009