C690 H1115 N177 O203 S6
2-133-Interleukin 2 (human reduced), 125-L-serine-
Aldesleukin is in Phase 3 development as an immune modulator for HIV infection.
(Compound details obtained from PubMed,1 Journal of Internal Medicine article,2 Proleukin Full Prescribing Information,3 and ClinicalTrials.gov4,5)
What is aldesleukin?
Aldesleukin is a drug that has been approved by the U.S. Food and Drug Administration (FDA) under the brand name Proleukin for the treatment of two types of cancers: renal cell carcinoma and melanoma.3 It is also being studied as an investigational drug to treat HIV infection.6
As an investigational HIV drug, aldesleukin belongs to a group of drugs called immune modulators.2 Immune modulators (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function.
Aldesleukin is a synthetic version of interleukin-2, which is a protein that is made naturally in the body. Interleukin-2 helps activate the immune system to make more immune cells and stimulates existing immune cells to fight infections, such as HIV infection.3,7
To learn how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.
Select clinical trials of aldesleukin
Study Name: NCT03308786Phase: 2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to see whether aldesleukin could decrease the number of resting CD4 cells within the latent HIV reservoir and reduce the size of the reservoir in individuals with viral suppression.8
Study Names: ANRS118; ILIADE; NCT00071890Phase: 2/3
Status: This study has been completed.
Locations: United States and France
Purpose: The purpose of this study was to see whether aldesleukin given before an analytical treatment interruption of antiretroviral therapy (ART) could extend the time that participants are temporarily off treatment and also keep their CD4 counts above 350 cells/mm3.9
Selected Study Results: Results published in AIDS (2012) showed that treatment with three cycles of aldesleukin given before a structured treatment interruption of ART in people with high CD4 counts and viral suppression allowed for a longer period off ART before the need for resuming ART, as compared to the control arm (no aldesleukin).10
Study Names: (1) ESPRIT; NCT00004978 and (2) SILCAAT; NCT00013611Phase: 3
Status: Both studies have been completed.
Locations: ESPRIT - multiple countries, including the United States; SILCAAT - United States
Purpose: The purpose of these studies was to evaluate whether aldesleukin plus ART could lower the risk of opportunistic infection and death in participants with HIV.4,5,11
Selected Study Results: Results of the ESPRIT and SILCAAT studies published in the New England Journal of Medicine (2009) showed that treatment with aldesleukin in combination with ART resulted in a substantial increase in CD4 counts, as compared with ART alone. However, the increase in CD4 counts seen with aldesleukin plus ART did not provide any clinical benefit in terms of lowering the risk of opportunistic disease and death.11
For more details on the studies listed above, see the Health Professional version of this drug summary.
A number of other HIV-related studies on aldesleukin have been conducted, including:
- The STALWART study (NCT00110812), a Phase 2 study which looked at the effects of aldesleukin with and without ART on CD4 counts in participants who were either off ART or who had never taken ART before. This study has been completed.12
- The ANRS 119 study (NCT00120185), a Phase 2 study which evaluated whether aldesleukin without ART could increase CD4 counts and delay the need to start ART in participants who were either off ART or who had never taken ART before. This study has been completed.13,14
- The COSMIC study, which looked at the effects of aldesleukin with and without ART on the latent HIV reservoir. This study has been completed.15
- NCT01013415, a Phase 1/2 study that is currently evaluating a combination HIV cure approach using aldesleukin in combination with an investigational gene therapy product. This study has been completed. Results were presented at CROI 2022.6
- NCT03346499, a Phase 1 study that evaluated an infusion of natural killer cells and aldesleukin in people on ART with viral suppression. This study has been completed.16
What side effects might aldesleukin cause?
One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of aldesleukin listed above.
ANRS118; ILIADE (NCT00071890):Many mild to moderate side effects associated with aldesleukin occurred in the first 24 weeks of this study. The most common side effects were weakness, fever, and nausea. Eleven participants receiving aldesleukin stopped the study early because of side effects related to aldesleukin. Overall, the few severe side effects that occurred during the study occurred more frequently in the aldesleukin group than in the ART-only group.10
ESPRIT (NCT00004978) and SILCAAT (NCT00013611):In these studies, serious side effects were more common in participants who received aldesleukin plus ART than in participants who received ART alone. Serious side effects that occurred in either the ESPRIT study or the SILCAAT study included heart and blood vessel disorders, gastrointestinal disorders, and psychiatric disorders.11
Because aldesleukin is still being studied in people with HIV, information on possible side effects of the drug is not complete. As testing of aldesleukin continues, additional information on possible side effects will be gathered.
Additional information on side effects that are known to be associated with aldesleukin can be found in the FDA-approved Full Prescribing Information for Proleukin.
Where can I get more information about clinical trials studying aldesleukin?
More information about aldesleukin-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests. To learn more about the ClinicalTrials.gov search features, please see How to Search.)
Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.
- National Center for Biotechnology Information. PubChem compound summary for SID: 7847813, aldesleukin. Accessed May 1, 2023
- Gougeon M, Chiodi F. Impact of γ-chain cytokines on T cell homeostasis in HIV-1 infection: therapeutic implications. J Intern Med. 2010;(267):502-514. Accessed May 1, 2023
- Clinigen Group PLC. Proleukin: full prescribing information, December 8, 2021. DailyMed. Accessed May 1, 2023
- National Institute of Allergy and Infectious Diseases (NIAID). A randomized, open-label, Phase III, international study of subcutaneous recombinant IL-2 in patients with HIV-1 infection and CD4+ cell counts 300/mm^3 or greater: evaluation of subcutaneous proleukin in a randomized international trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 10, 2000. NLM Identifier: NCT00004978. Accessed May 1, 2023
- University of Minnesota. 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: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 24, 2001. NLM Identifier: NCT00013611. Accessed May 1, 2023
- University of Pennsylvania. A Phase I/II study of the safety, survival, and trafficking of autologous CD4-ZETA gene-modified T cells with and without extension interleukin-2 in HIV infected patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 5, 2009. NLM Identifier: NCT01013415. Accessed May 1, 2023
- Paredes R, López Benaldo de Quirós J, Fernández-Cruz E, Clotet B, Lane H. The potential role of interleukin-2 in patients with HIV infection. AIDS Rev. 2002;4(1):36-40. Accessed May 1, 2023
- Case Western Reserve University. HIV reservoir reduction with interleukin-2. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 29, 2017. NLM Identifier: NCT03308786. Accessed May 1, 2023
- National Institute of Allergy and Infectious Diseases (NIAID). Phase II/III study evaluating the effect of IL-2 on preservation of the CD4 T-lymphocytes after interruption of anti-retroviral tx in HIV infected patients with CD4 T-lymphocyte count greater than 500 cells/mm(3) who have received anti-retroviral tx. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 3, 2003. NLM Identifier: NCT00071890. Accessed May 1, 2023
- Lévy Y, Thiébaut R, Gougeon ML, et al. Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV. AIDS. 2012;26(6):711. Accessed May 1, 2023
- Abrams D, Lévy Y, Losso M, et al. Interleukin-2 therapy in patients with HIV infection. N Engl J Med. 2009;361(16):1548-1559. Accessed May 1, 2023
- National Institute of Allergy and Infectious Diseases (NIAID). STALWART: a randomized, open-label, international study of subcutaneous recombinant interleukin-2 with and without concomitant antiretroviral therapy in patients with HIV-1 infection and CD4+ cell counts of 300 cells/mm3 or more. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 13, 2005. NLM Identifier: NCT00110812. Accessed May 1, 2023
- Molina JM, Levy Y, Fournier I, et al. Interleukin-2 before antiretroviral therapy in patients with HIV infection: a randomized trial (ANRS 119). J Infect Dis. 2009;200(2):206-215. Accessed May 1, 2023
- French National Agency for Research on AIDS and Viral Hepatitis. Study of the immunological efficacy of using subcutaneous interleukin-2 (IL-2) in antiretroviral naive HIV-1-infected subjects with a CD4 cell count above 300/mm3. ANRS 119 Trial INTERSTART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 8, 2005. NLM Identifier: NCT00120185. Accessed May 1, 2023
- Stellbrink HJ, van Lunzen J, Westby M, et al. Effects of interleukin-2 plus highly active antiretroviral therapy on HIV-1 replication and proviral DNA (COSMIC trial). AIDS. 2002;16(11):1479-1487. Accessed May 1, 2023
- University of Minnesota - Clinical and Translational Science Institute. Adoptive transfer of haploidentical natural killer cells and IL-2 in human immunodeficiency virus (HIV). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 24, 2017. NLM Identifier: NCT03346499. Accessed May 1, 2023
Last Reviewed: May 1, 2023