INCLUSION CRITERIA FOR PATIENTS NOT INCLUDED UNDER THE TREATMENT INTERRUPTION ARM:
1. Adult (18 years old or older).
2. Eligibility to undergo leukapheresis procedures.
3. Willingness to give informed consent for the storage of blood or
tissue samples and HLA testing.
4. AND at least one of the following:
An HIV-seropositive patient categorized as an LTNP as defined by clinical and laboratory criteria, regardless of HLA class I type.
HIV-seropositive HLA B*27+, B*35+, B*44+, B*57+, B*58+ and/or A*02+ progressors.
HIV-seropositive patients possessing sera with broadly cross-neutralizing antibody activity to HIV.
Persons who are seronegative for HIV but are family members of seropositive patients exhibiting immunologic control of HIV.
EXCLUSION CRITERIA FOR PATIENTS NOT INCLUDED UNDER THE TREATMENT INTERRUPTION ARM:
1. Pregnant women.
2. Cardiovascular instability, severe anemia, inadequate venous access, severe coagulation disorder or any other condition that the Principal Investigator or Apheresis Unit staff considers a contraindication to the leukapheresis procedure.
INCLUSION CRITERIA FOR PATIENTS CONSENTING TO UNDERGO A TREATMENT INTERRUPTION:
1. Subjects greater than or equal to 18 years of age.
2. HIV infection confirmed by ELISA and Western blot.
3. Ability to sign informed consent and willingness to comply with study requirements and clinic policies.
4. In the judgment of the PI, patient has satisfactory knowledge of the benefits of continuing HAART as well as the risks of discontinuing such treatment. The patient has a private physician and the decision to interrupt antiretroviral therapy, the target point (i.e. viral load or CD4+ T cell count) to reinitiate therapy, and the regimen of antiretrovirals used upon re-initiation of therapy will be made with this private physician.
5. History of at least 2 months of ongoing HAART, defined as a minimum three drug regimen consisting of at least two nucleoside analogs and one or two protease inhibitors or two nucleoside analogs and one non-nucleoside reverse transcriptase inhibitor (NNRTI) or three nucleosides in place of other drug classes OR patients that are currently off therapy who are planning on resuming or initiating a HAART regimen within the next 3 months.
6. No baseline CD4+ T cell counts less than or equal to 350 cells/micro liters, with confirmation, within the last 3 months.
7. Asymptomatic for significant HIV-related illnesses, such as opportunistic infections and malignancies other than mucocutaneous Kaposi's sarcoma.
8. For patients on IL-2 therapy, agreement to resume HAART while undergoing treatment cycles.
9. Eligibility to undergo leukapheresis procedures.
EXCLUSION CRITERIA FOR PATIENTS CONSENTING TO UNDERGO A TREATMENT INTERRUPTION:
1. Psychiatric illness that, in the opinion of the PI, might interfere with study compliance.
2. Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or compromise patient safety.
3. Women who are pregnant or breastfeeding.
4. Creatinine greater than 2 mg/dL.
5. Platelet count less than 100,000/mm(3), hemoglobin less than 9 mg/dL, neutrophils less than 750/mm(3).
6. PT or PTT (in the absence of documented anti-cardiolipin antibody) prolonged by greater than 2 seconds.
7. Known underlying bleeding disorder.
8. Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine history, physical examination, or screening laboratory studies.
9. Documented history of virologic relapse in the past year following interruption of HAART therapy.
10. History of significant opportunistic infection or HIV-associated malignancy.
11. Patient must not ever have had a total CD4 count of less than or equal to 150 cells/cubic millimeter during the year prior to enrollment. At least 2 measurements, possibly including the measurement during the screening visit and/or H& P visit, must be available.
12. Due to a possible increased risk of hypersensitivity reaction, patients on an abacavir-containing regimen will not be eligible for treatment interruption.
13. Patients with chronic hepatitis B infection requiring receiving treatment with 3TC (lamivudine), adefovir or tenofovir for suppression are not eligible for this study.
14. Cardiovascular instability, severe anemia, inadequate venous access, severe coagulation disorder or any other condition that the Principal Investigator or Apheresis Unit staff considers a contraindication to the leukapheresis procedure.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009