A Randomized, Open-Label, International Study of Subcutaneous Recombinant Interleukin-2 (rIL-2, Aldesleukin) with and without Concomitant Antiretroviral Therapy in Patients with HIV-1 Infection and CD4+ Cell Counts = 300/mm3: Study of Aldesleukin with and without Antiretroviral Therapy (ESPRIT 002: STALWART) - STALWART

Phase 1

• Conditions: HIV infection

• Registration Number: EUCTR2005-001490-95-DE
• Lead Sponsor: ational Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-04-16
• Study Completion: 2009-02-28
• Last Update Posted: 4 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 469

Inclusion Criteria

1. Documented HIV-1 infection by any licensed ELISA test and confirmed by a second method (e.g., Western Blot); or any one of the following prior to randomization: detectable HIV p24 antigen, quantifiable plasma HIV RNA, or proviral DNA.
2. = 18 years of age (children are not eligible for study participation because data on rIL-2 in pediatric HIV disease is limited, and more data on the effects of rIL-2 in the absence of antiretrovirals should be gathered in adults before exposing pediatric patients to these risks).
3. The following clinical laboratories obtained within 45 days before randomization:
a. One CD4+ T cell count = 300 cells/mm3 (For participants who are status post-splenectomy, also a CD4+ cell percentage on this occasion = 20%).
b. AST or ALT < 5 X the upper limit of normal (ULN) range.
c. Total or direct bilirubin = 2 X ULN (Participants with hyperbilirubinemia due to Gilbert’s syndrome may have a serum bilirubin up to 5 X ULN).
d. Serum creatinine = 2 mg/dl (177 µmol/L).
e. Sodium within normal limits.
f. Granulocyte count = 1000/mm3.
g. Hemoglobin = 10 gm/dl.
h. Platelet count = 50,000 cells/mm3.
4. Ability to provide informed consent.
5. Ability to obtain HAART regimens consisting of = 1 protease inhibitor and = 2 nucleoside or nucleotide reverse transcriptase inhibitors.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any prior history of rIL-2 use
2. Use of any approved or experime.ntal antiretroviral drug (including hydroxyurea) within one year prior to randomization.
3. In the judgment of the clinician, any current indication for continuous antiretroviral therapy, or any contraindication to antiretroviral therapy.
4. Evidence of virological failure on a protease inhibitor or nonnucleoside reverse transcriptase - based antiretroviral regimen.
5. Use of systemic corticosteroids, chemotherapy, or experimental cytotoxic drugs within 45 days prior to randomization.
6. Use of any agent (approved or experimental) with clinically significant immunomodulatory effects within 8 weeks prior to randomization.
7. History of any AIDS-defining illness (category C., CDC, 1993) or any of the following conditions: extrapulmonary Pneumocystis carinii disease; multi-dermatomal Herpes zoster (= 10 lesions in a non-contiguous site); American trypanosomiasis (Chagas disease) of the CNS; Penicillium marneffii disease; visceral leishmaniasis; non-Hodgkin’s lymphoma of any cell-type; Hodgkin’s lymphoma; bartonellosis; microsporidiosis (> 1 month’s duration); nocardiosis; invasive aspergillosis; or Rhodococcus equi disease.
8. Concurrent malignancy requiring cytotoxic chemotherapy.
9. Any CNS abnormality that requires ongoing treatment with antiseizure medication.
10. Current or historical autoimmune/inflammatory diseases including:
a. Inflammatory bowel disease
b. Psoriasis
c. Optic neuritis
d. Any autoimmune/inflammatory diseases with potentially life-threatening complications
11. Significant cardiac, pulmonary, renal, hepatic, gastrointestinal, CNS, or psychiatric disease or illicit substance use/abuse that in the opinion of the investigator would make the participant a poor candidate for study participation.
12. Pregnancy (for women of childbearing potential, a negative pregnancy test, urine or serum, is required within 14 days prior to randomization).
13. Breastfeeding.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the change from baseline in CD4+ T lymphocyte count after 32 weeks in groups of participants randomly assigned to receive no therapy (no antiretrovirals or rIL-2), subcutaneous rIL-2 monotherapy or subcutaneous rIL-2 with pericycle HAART.;Secondary Objective: To compare among the three treatment groups after 32 weeks:<br>1. incidence of grade 3 and 4 events .<br>2. number of therapy modifications .<br>3. mean plasma HIV RNA changes from baseline (evaluated at 32 weeks and 12 months).<br>4. mean CD4+ T lymphocyte changes from baseline at 12 months.<br>5. changes in HIV genotyping that may represent development of antiretroviral drug resistance.<br>6. selected lipid, thyroid, and hepatic abnormalities.;Primary end point(s): The primary endpoint will be mean change in CD4+ T lymphocyte count from baseline (average of two pre-randomization counts) to 32 weeks in the three study groups.