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Immunologic and Virologic Response in HIV Infected Progressors After Infusion of Lymphocytes From HIV Infected "Elite" Long-Term Non-Progressors


Phase 1
18 Years
N/A
Open (Enrolling)
Both
HIV Infections

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Trial Information

Immunologic and Virologic Response in HIV Infected Progressors After Infusion of Lymphocytes From HIV Infected "Elite" Long-Term Non-Progressors


Improvements in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)
treatments in the United States have made the disease in many cases a chronic illness.
However, many individuals have failed multiple lines of standard therapy, and thus,
development of new modes of salvage treatment is crucial. Restriction of viral replication,
mediated by CD8+ cells, appears to play an important role in control of HIV replication. A
subset of individuals, many of whom possess human leukocyte antigen (HLA) - B*57 exhibit
restriction of HIV type 1 viral replication to less than 50 copies/mL, presumably by a
mechanism that is CD8+ T-cell mediated, and become elite long-term non-progressors (LTNP),
who have no evidence of progressive immunodeficiency and no development of opportunistic
complications during many years of follow-up. Other individuals, including those with
HLA-B*57 show no evidence of control of HIV replication, and without antiretroviral therapy
will develop progressive immunodeficiency and HIV-related opportunistic complications. In
this exploratory study, we are investigating a novel cell transfer strategy: up to 3
patients with HIV infection have failed at least 2 standard regimens of antiretroviral
therapy, have a CD4+ count under 200 cells/mm (3), and a plasma HIV viral load of greater
than 10,000 copies/mL, will be administered 10 (10) peripheral blood mononuclear cells
obtained by lymphapheresis from an "elite" LTNP matched to the recipient on at least one
HLA-B allele. Up to 70 patients may be enrolled for screening to identify 3 donors and 3
recipients. Up to 3 infusions may be administered per patient, with each infusion occurring
no more frequently than every 3 months. The primary endpoints will be the safety of the
infusions and the survival of donor cells in the recipient. Changes in the recipient's CD4+
and CD8+ cell number, other immune parameters, and plasma HIV viral load will also be
monitored closely for evidence of anti-HIV activity.

Inclusion Criteria


- 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

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 available optimized combination antiretroviral
therapy, to include at least 3 drugs, one of which is a non-nucleoside reverse
transcriptase inhibitor (NNRTI), integrase inhibitor, 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 or intolerance of at least two previous combination antiretroviral regimens.
Failure will be defined as an HIV viral load greater than 400 copies/mL while taking a
given regimen.

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.

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.

Matched to at least one HLA-B allele of the potential recipient. The

match will be at a two-digit resolution HLA allele level of typing or higher.

Hematocrit greater than or equal to 30 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, HBV/HCV NAT, HTLV-I/II
antibodies, T.cruzi antibodies, HBsAg, or serologic test for syphilis (with positive
confirmatory treponemal-based assay), unless the patient has received adequate therapy for
syphilis. Donors with a positive West Nile Virus NAT are deferred for 120 days.

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

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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety, survival of transferred cells.

Principal Investigator

Joseph A Kovacs, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institutes of Health Clinical Center (CC)

Authority:

United States: Federal Government

Study ID:

080024

NCT ID:

NCT00559416

Start Date:

November 2007

Completion Date:

Related Keywords:

  • HIV Infections
  • HIV/AIDS
  • HLA-B*57
  • Cell Transfer
  • Resistant Virus
  • Drug Resistance HIV
  • Drug Failure
  • Raltegravir Failure
  • Lymphocyte Infusion
  • Long-Term Non-Progressor (LTNP)
  • LTNP
  • HIV
  • treatment experienced
  • HIV Infections
  • Acquired Immunodeficiency Syndrome

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892