A Phase 2 interventional study of Recombinant Interleukin-2 in HIV Infection, sponsored by Case Western Reserve University. Terminated at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-09-28.
Sponsored by Case Western Reserve University · Phase 2, Interventional, and Basic science
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).
Interleukin-2 (IL-2) has been extensively studied in HIV infected individuals with no demonstrated clinical benefit as far as improving survival or decreasing risk of progression to AIDS. The results of the two landmark, international, multicenter, phase III, randomized trials of IL-2 in HIV infected participants (SILCAAT and ESPRIT) have been recently published. These trials, which started more than a decade ago, enrolled over 5800 participants who were randomized to anti-retroviral therapy (ART) +/- IL-2 and showed no benefit to IL-2 treatment in survival or progression to AIDS. Many individuals with HIV infection can lead normal lives on ART but replication-competent virus remains within resting CD4+ cells, referred to as the "HIV reservoir". There is a renewed interest in strategies to decrease or eliminate the viral reservoir in an attempt to provide a sterilizing or a functional "cure" for HIV that would allow the discontinuation of ART, which currently must be taken life-long. These therapies have long-term metabolic and cardiovascular toxicities as well as substantial cost. More recent data suggest that IL-2 administration may decrease the size of the HIV reservoir, getting ART-treated participants closer to levels of HIV persistence that may ultimately allow for sterilizing or functional cure.
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).
Exclusion Criteria:
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.
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.
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.
Subcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles, in addition to combination antiretroviral therapy.
Drug: Recombinant Interleukin-2
Subcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles
Also known as: IL2, IL-2, rIL2, aldesleukin
Latent HIV Reservoir Change by QVOA
Change in the number of infectious units per million resting CD4+ T cells (IUPM) from baseline to the end of study treatment, as measured by the Quantitative Viral Outgrowth Assay (QVOA).
Time frame: 15 months
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by Intact Proviral DNA.
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the intact proviral DNA assay.
Time frame: 15 months
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by the Tat-rev Inducible Limiting Dilution Assay (TILDA).
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the Tat-rev inducible limiting dilution assay (TILDA).
Time frame: 15 months
Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by the Envelope Detection by Induced Transcription-based Sequencing (EDITS)
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the Envelope Detection by Induced Transcription-based Sequencing (EDITS).
Time frame: 15 months
In Vivo Induction of HIV Expression in Vivo as Measured by the Envelope Detection by Induced Transcription-based Sequencing (EDITS)
Number of inducible cell-associated HIV mRNA copies per million CD4+ T cells at the beginning and end of rIL2 cycles 1, 4, and 8.
Time frame: 15 months
Plasma HIV RNA During rIL2 Exposure
Plasma HIV RNA copies/mL by PCR at the beginning and end of rIL2 cycle 1.
Time frame: baseline, day 7
Natural Killer (NK) Cell Phenotype During rIL2 Exposure
Change in the percent of NK cells expressing CD16+CD56+ by flow cytometry from baseline to the end of study treatment.
Time frame: baseline, day 7
Natural Killer (NK) Cell Phenotype During rIL2 Exposure
Change in the percent of NK cells expressing CD56+CD16- by flow cytometry from baseline to the end of study treatment.
Time frame: baseline, day 7
| Milestone | IL2 Treatment |
|---|---|
| Started | 9 |
| Completed | 0 |
| Not completed | 9 |
| Withdrew: Study terminated after discussion with safety monitoring committee | 9 |
Change in the number of infectious units per million resting CD4+ T cells (IUPM) from baseline to the end of study treatment, as measured by the Quantitative Viral Outgrowth Assay (QVOA).
No measurements were reported for this outcome.
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the intact proviral DNA assay.
No measurements were reported for this outcome.
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the Tat-rev inducible limiting dilution assay (TILDA).
No measurements were reported for this outcome.
Correlation coefficient between measures of the latent HIV reservoir by QVOA and measures of the latent HIV reservoir by the Envelope Detection by Induced Transcription-based Sequencing (EDITS).
No measurements were reported for this outcome.
Number of inducible cell-associated HIV mRNA copies per million CD4+ T cells at the beginning and end of rIL2 cycles 1, 4, and 8.
No measurements were reported for this outcome.
Plasma HIV RNA copies/mL by PCR at the beginning and end of rIL2 cycle 1.
| RNA copies/mL | IL2 Treatment |
|---|---|
| baseline | 10 ± 0 |
| day 7 | 298 ± 522 |
Change in the percent of NK cells expressing CD16+CD56+ by flow cytometry from baseline to the end of study treatment.
| percentage of cells | IL2 Treatment |
|---|---|
| baseline | 28.8 (19.8 to 37.5) |
| day 7 | 35.8 (30.9 to 39.2) |
Change in the percent of NK cells expressing CD56+CD16- by flow cytometry from baseline to the end of study treatment.
| percentage of cells | IL2 Treatment |
|---|---|
| baseline | 4.5 (3.1 to 5.2) |
| day 7 | 12.7 (8.3 to 17.1) |
Collected over Adverse event data were collected until the study was terminated. This period was the time between enrollment into the study and study termination. The duration ranged from 8.3 months to 14.6 months,.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| IL2 Treatment | 0/9 (0%) | 1/9 (11.1%) | 2/9 (22.2%) |
| Event | IL2 Treatment |
|---|---|
| suspected capillary leak syndromeVascular disorders | 1/9 |
| Event | IL2 Treatment |
|---|---|
| biochemical hypothyroidismEndocrine disorders | 2/9 |
| Age, Categorical(Participants) | IL2 Treatment |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 9 |
| >=65 years | 0 |
| Age, Continuous(years) | IL2 Treatment |
|---|---|
| Median | 49 (35 to 64) |
| Sex: Female, Male(Participants) | IL2 Treatment |
|---|---|
| Female | 0 |
| Male | 9 |
| Ethnicity (NIH/OMB)(Participants) | IL2 Treatment |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 8 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | IL2 Treatment |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 6 |
| More than one race | 1 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | IL2 Treatment |
|---|---|
| United States | 9 |
| CD4+ T cell count ≥ 350 cells/mm^3(cells/mm^3) | IL2 Treatment |
|---|---|
| Median | 808 (478 to 1230) |
| HIV-1 RNA < 50 copies/mL obtained within 60 days prior to study entry(Participants) | IL2 Treatment |
|---|---|
| Count of participants | 9 |
1 further baseline measures are reported on the registry.
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Case Western Reserve University