At a glance
ClinicalIndex Comparison Record- ✓On stable antiretroviral therapy (≥2 agents) for ≥4 months with no change in regimen; if only 2 agents, at least one must be a protease inhibitor
- ✓Documented HIV-1 infection by ELISA/Western blot or detectable viral load
- ✓CD4+ T cell count 50-299 cells/mm3 (mean of 2 measurements within 4 months of randomization)
- ✓Viral load <10,000 copies/mL at 2 time points within 4 months of randomization
- ✕Prior IL-2 therapy or participation in prior/ongoing IL-2 trials
- ✕Most AIDS-defining illnesses; limited exceptions for successfully treated lymphoma (≥5 years remission), esophageal candidiasis (12 months off antifungal), cervical cancer (≥5 years), stable mucocutaneous KS (≥12 months), resolved TB/M. kansasii (≥12 months), PCP/recurrent pneumonia/Salmonella (≥12 months), stable wasting (≥12 months), resolved CNS toxo (≥12 months), resolved cryptosporidiosis/isosporiasis (≥12 months)
- ✕Autoimmune disease, inflammatory bowel disease, psoriasis, optic neuritis, congestive heart failure, active ischemic heart disease, uncontrolled diabetes, hemophilia, seizure disorder, uncontrolled hypothyroidism, cirrhosis, prior transplantation
- ✕Systemic corticosteroids or immunomodulatory agents within 4 weeks; cytotoxic agents/antimetabolites within 4 weeks; hydroxyurea or IVIG within 4 months
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A Phase III Multicenter Randomized Study of the Biological and Clinical Efficacy of Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients With Low CD4+ Counts Under Active Antiretroviral Therapy (SILCAAT Amendment 4)
In Brief
A Phase 3 clinical trial evaluating Proleukin for HIV Infection. Completed, enrolled 1,695 participants across 1 site.
Detailed Summary
This study will examine whether interleukin-2 (IL-2) plus antiretroviral therapy (ART) slows HIV disease progression in patients with low CD4+ T cell counts compared with patients taking ART alone. CD4+ T cells are a subset of lymphocytes-white blood cells that are part of the body's immune system. IL-2 is a protein that is naturally produced by lymphocytes. Given in intermittent cycles, IL-2 can raise CD4+ T cell counts in some HIV-infected patients taking antiretroviral drugs. This study will examine whether the increase in CD4+ T cells lowers the risk of AIDS-related illnesses and death. HIV-infected patients 18 years of age and older with a viral load under 10,000 copies per milliliter and a CD4+ T cell count between 50 and 299 cells per cubic millimeter who are taking antiretroviral therapy and who have not previously received IL-2 therapy may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests. Participation in the study will be from 4.5 to 6 years, depending on what point in the duration of the study the individual patient is enrolled. Patients will be randomly assigned to receive IL-2 plus ART or ART alone. All participants will be advised individually about the best ART regimen for them. Patients in the IL-2 treatment group will be taught how to self-inject IL-2 under the skin (similar to insulin injections). They will inject IL-2 twice a day for 5 days every 8 weeks for the first year (until week 49 of the study). From week 49 on they may receive 5-day cycles of IL-2 every 4 months when needed to maintain CD4+ T cell count elevations. An extra cycle may be given 2 months after the week 49 follow-up visit (see follow-up schedule below), depending on their CD4+ T cell count. Patients whose cell counts have not increased after 12 to 16 months of IL-2 treatment will discuss with the doctor the possibility of stopping IL-2. Those who do stop IL-2 treatment will be asked to remain in the study for follow-up evaluations. All patients will be followed in the clinic every 2 months for the first year of the study (weeks 1, 9, 17, 25, 33, 41 and 49) and every 4 months during years 2-6 for a brief history and physical exam, urine and blood tests, return of diary cards (record of drug side effects) and medication review. During the visits from the second year on, patients will also be asked about their ability to do certain ordinary tasks, such as taking care of themselves; ...
Study Details
Timeline
Interventions
Recombinant IL-2 was given at a dose of 4.5 MIU twice daily subcutaneously for 5 consecutive days every 8 weeks, in addition to antiretroviral therapy, for 6 cycles. After the first 6 cycles, additional cycles were given to either achieve or maintain the patient's CD4+ cell count goal.