HIV Reservoir Reduction With Interleukin-2
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: Recombinant Interleukin-2
Intervention description: Subcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles
Intervention MeSH terms: Aldesleukin; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this pilot study is to examine the effects of eight 4-day cycles of
      subcutaneous recombinant interleukin-2 (rIL-2) given every 8 weeks on levels of
      replication-competent HIV in CD4 cells and on the size of HIV viral reservoir in up to 20
      participants with chronically suppressed HIV infection (viral load <50 copies/mL).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent signed and dated by study participant.

          2. Male or female, at least 18 years of age and not older than 65 years of age.

          3. HIV-1 infection, documented by and FDA-approved ELISA, EIA, or rapid antibody
             detection method, and confirmed by a second approved antibody-based test or by a
             positive approved HIV RNA detection assay.

          4. CD4+ T cell count ≥ 350 cells/mm3;

          5. HIV-1 RNA < 50 copies/mL obtained within 60 days prior to study entry performed with
             an FDA-approved HIV-1 RNA assay.

          6. Adequate venous access and no other contraindications for leukapheresis

          7. Absolute neutrophil count (ANC) > 2000/mm3

          8. Hemoglobin level >10 g/dL (males); > 9.5 g/dL (females)

          9. Platelet count >150,000/mm3

         10. Serum creatinine <1.5 mg/dL

         11. AST and ALT <2.5 times the upper limit of normal

         12. TSH, T3, and T4 levels within the normal range of the processing laboratory.

         13. Anti-thyrosine peroxidase (TPO) within the normal range of the processing laboratory.

         14. Willing to comply with study-mandated evaluations; including not changing
             antiretroviral regimen (unless medically indicated) during the study period.

         15. All participants must have received HAART, and had viral loads below the limit of
             quantification of the assay for at least 1 year. Participants who had intermittent
             isolated episodes of detectable low-level viremia < 500 copies RNA/mL flanked by viral
             loads below the limit of quantification of the assay will remain eligible.

         16. On a stable 3-drug combination antiretroviral regimen (no changes to treatment within
             4 weeks of enrollment) and willing to continue on current antiretroviral therapy for
             the duration of the study, unless otherwise medically indicated. The study principal
             investigator can approve a 2-drug antiretroviral regimen on a case-by-case basis.

        Exclusion Criteria:

          1. Childbearing potential for female participants. For the purposes of this study, a
             woman is considered to be of childbearing potential if she is postmenarche, has not
             had a documented surgical sterilization procedure, has an intact uterus and at least 1
             ovary, and has had a spontaneous menstrual period in the last 2 years.

          2. Acute or chronic hepatitis C infection, defined as a positive plasma HCV RNA using any
             FDA-approved qualitative or quantitative test in a participant with a positive HCV
             antibody (HCV RNA testing is not required in participants with a negative HCV
             antibody). Participants who have completed a course of a direct-acting antiviral agent
             for hepatitis C and have a confirmed plasma HCV RNA level below the limit of detection
             of the assay 12 weeks or longer after completion of therapy will be eligible.

          3. Acute or chronic hepatitis B infection, defined as a positive HBV surface antigen or a
             positive HBV DNA.

          4. History of advanced chronic liver disease, including cirrhosis, advanced liver
             fibrosis, severe portal hypertension, or manifestations or hepatic failure.

          5. History of malignant disease that is not considered to be surgically or medically
             eradicated or that has required any form of therapy in the past 5 years.

          6. Current diagnosis of congestive heart failure of any severity, uncontrolled angina or
             uncontrolled arrhythmias.

          7. History of chronic lung disease that has required pharmacologic treatment, oxygen
             supplementation, medical monitoring, or hospitalization in the previous year, or that
             is expected to cause persistent or recurrent pulmonary symptoms or impairment.
             Examples of the latter include but are not limited to chronic bronchitis, emphysema,
             and pulmonary fibrosis.

          8. History or any features on physical examination indicative of a bleeding diathesis.

          9. History or current diagnosis of thromboembolic disease, including deep vein thrombosis
             and pulmonary embolism, or family history of the same.

         10. History of hypersensitivity to radiological contrast media or anticipated need for
             exposure to radiological contrast media during the study period.

         11. Use of chronic corticosteroids, hydroxyurea, or immune-modulating agents (e.g.,
             interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors,
             etc.) within 30 days prior to enrollment.

             NOTE: Use of inhaled or topical steroids is not exclusionary.

         12. Breast-feeding.

         13. Use of aspirin, warfarin or any other antithrombotic or antiplatelet agent during the
             2-week period prior to leukapheresis.

         14. History of autoimmune disorders, including but not limited to Crohn's disease,
             scleroderma, thyroiditis, inflammatory arthritis, myasthenia gravis,
             glomerulonephritis, systemic lupus erythematous, and vasculitis.

         15. Type 1 diabetes mellitus.

         16. History of thyroid disease that has required antithyroid or thyroid hormone
             replacement therapy at any time in the past.

         17. Current continued use, or anticipated continued medical indication for nephrotoxic
             agents, including but not limited to aminoglycosides and other potentially nephrotoxic
             antimicrobials, indomethacin, high scheduled doses of other NSAIDs, and lithium salts.

             NOTE: Low doses or limited duration of these agents (i.e., ≤14 days) is not
             exclusionary.

         18. Current continued use, or anticipated continued medical indication for hepatotoxic
             agents, including but not limited to amiodarone, methotrexate, and anticonvulsants and
             antimicrobials with elevated hepatotoxic potential.

             NOTE: Low doses or limited duration of these agents (i.e., ≤14 days) is not
             exclusionary.

         19. Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements.

         20. Serious illness requiring systemic treatment and/or hospitalization within 30 days
             prior to study entry that in the judgement of the investigator may compromise study
             participation or pose additional risks to the participant.

         21. Any other condition that, in the opinion of the clinical investigator or sponsor,
             might compromise any aspect of this trial.