What Is an Investigational Drug?
An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
To learn more about investigational drugs, read the AIDS_info_ What is an Investigational HIV Drug? fact sheet.
What Is Aldesleukin?
Aldesleukin is a drug that has been approved by FDA for the treatment of 2 types of cancers called renal cell carcinoma and melanoma.3
Aldesleukin is also being studied as an investigational drug for HIV infection. As an HIV therapy, aldesleukin is categorized as an immune modulator.2 Immune modulators (also called immunomodulators) are substances that modify (activate, enhance, or suppress) the functioning of the immune system.
HIV infection can make a person's immune system not work properly over the course of the viral infection. When this happens:
- CD4 counts can drop and HIV infection can worsen.
(A CD4 count is a laboratory test that measures the number of CD4 cells -- a type of immune cell -- in a sample of blood and is an important indicator of immune function.)
- Other immune system cells or proteins may not be produced in normal amounts and may not work normally.
- A person may not respond well to antiretroviral therapy (ART).
(ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from multiplying.)
- latent HIV reservoirs can form and persist in the body.
(latent HIV reservoirs are "resting" CD4 cells or other cells that are infected with HIV but not actively producing HIV in the body. Because ART does not work against HIV that's hidden in latent reservoirs, these reservoirs are one of the main obstacles to curing HIV infection.)6-10
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.3,11 Researchers have studied whether aldesleukin can increase the number and survival of immune cells and boost the immune system. Aldesleukin has also been studied as part of a strategy to reduce the latent HIV reservoir.12-15
How Are Clinical Trials of Investigational Drugs Conducted?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.16
- Phase I trials: Researchers test an investigational drug in a small group of people (20-80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100-300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug is administered to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.16
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA's accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug's risks, benefits, and optimal use.16 (Some clinical trials are categorized as "a" or "b," such as "Phase Ia" or "Phase IIb." These different sublevels typically mean that a study is researching certain types of information or using a certain type of participant population.)
In What Phase of Testing Is Aldesleukin?
As an immune modulator for HIV infection, aldesleukin has been studied in Phase III clinical trials.4,5
What Are Some Studies On Aldesleukin?
Study Names: ANRS118; ILIADE; NCT00071890
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Location: United States and France
- Participants were HIV-infected adults who had taken ART before (treatment-experienced) and who had been on ART for at least 12 months.
- Participants were not experiencing any HIV-related symptoms.
- Participants had Viral loads of less than 50 copies/mL. (Viral load is the amount of HIV in a sample of blood.)
- Participants had CD4 counts of at least 500 cells/mm3 for the 3 months before screening, and their lowest CD4 count since being diagnosed with HIV was 200 cells/mm3 or higher.
Purpose: The purpose of this study was to see whether aldesleukin could help extend participants' time off ART and help keep participants' CD4 counts above 350 cells/mm3 during an ART treatment interruption that followed. (A treatment interruption is a planned break from HIV medicines to evaluate how well an investigational drug can maintain control of a participant's viral load during a clinical trial.)17
Study Names: ESPRIT; NCT00004978
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Location: Multiple countries, including United States
- Participants were HIV-infected adults who were already on ART or who were starting ART when they began the study.
- Participants had CD4 counts of at least 300 cells/mm3 within 45 days of beginning the study.
Purpose: The purpose of this study was to evaluate whether aldesleukin plus ART could lower the risk of opportunistic infections and death in HIV-infected participants. (Opportunistic infections are infections that occur more often or are more severe in people with weakened immune systems than in people with healthy immune systems.)4,12
Study Name: SILCAAT; NCT00013611
Sponsor: University of Minnesota - Clinical and Translational Science Institute
Location: United States
Participants were HIV-infected adults who were already on ART for at least 4 months before they began the study.
Participants had viral loads of less than 10,000 copies/mL and CD4 counts between 50 and 299 cells/mm3.
Purpose: The purpose of this study was to evaluate whether aldesleukin plus ART could lower the risk of opportunistic infections and death in HIV-infected participants.5,12
For more details on the studies listed above, see the Health Professional version.
A number of other HIV-related studies on aldesleukin have been completed. These include:
- The STALWART study (NCT000110812), which looked at the effects of aldesleukin with and without ART on CD4 counts in participants who were either off ART or had never taken ART before (treatment-naive).18,19
- The ANRS 119 study (NCT00120185), which evaluated whether aldesleukin without ART could increase CD4 counts and push back the need for ART in participants who were either off ART or treatment-naive.20,21
- The COSMIC study, which looked at the effects of aldesleukin with and without ART on latent HIV.14
A Phase I/II study (NCT01013415) is currently evaluating a combination HIV cure approach that uses an investigational gene therapy product plus aldesleukin.15,22
What Side Effects Might Aldesleukin Cause?
In the ANRS118 study discussed under the previous question, a high number of mild to moderate side effects associated with aldesleukin occurred in the first 24 weeks of the 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, a low number of severe side effects occurred during the study, but they occurred more frequently in the aldesleukin group than in the ART-only group.23
In the ESPRIT (NCT00004978) and SILCAAT (NCT00013611) 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 or SILCAAT studies included heart and blood vessel disorders, gastrointestinal disorders, and psychiatric disorders.12,24
Because aldesleukin is still being studied, 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.
Where Can I Get More Information About Clinical Trials Studying Aldesleukin?
More information about aldesleukin-related research studies is available from the AIDS_info_ database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.
I Am Interested in Participating in a Clinical Trial of Aldesleukin. How Can I Find More Information About Participating in a Clinical Trial?
Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.16
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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/110942-02-4. Last accessed on October 30, 2016.
- Gougeon ML, Chiodi F. Impact of γ-chain cytokines on T cell homeostasis in HIV-1 infection: therapeutic implications. J Intern Med. 2010 May; 267(5): 502-14. Available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2010.02221.x/full. Last accessed on October 30, 2016.
- Novartis Pharmaceuticals Corporation. PROLEUKIN- aldesleukin injection: Full Prescribing Information, December 26, 2009. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a588140c-f9ed-4a9b-a9a6-bf3daafd8a5a. Last accessed on October 30, 2016.
- 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. Available at: https://clinicaltrials.gov/ct2/show/NCT00004978. Last accessed on October 30, 2016.
- University of Minnesota - Clinical and Translational Science Institute. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT00013611. Last accessed on October 30, 2016.
- Barouch DH, Deeks SG. Immunologic Strategies for HIV-1 Remission and Eradication. Science. 2014 Jul 11; 345(6193): 169-174. Available at: www.ncbi.nlm.nih.gov/pmc/articles/PMC4096716/. Last accessed on October 30, 2016.
- Lederman MM, Rodriguez B, Sieg S. Immunopathogenesis of HIV Infection. In: Coffey S and Volberding P, eds. HIV InSite Knowledge Base. University of California San Francisco; 2004. Available at: http://hivinsite.ucsf.edu/InSite?page=kb-00&doc=kb-02-01-04. Last accessed on October 30, 2016.
- Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother. 2001 May; 12(3): 133-50. Available at: www.ncbi.nlm.nih.gov/pubmed/12959322. Last accessed on October 30, 2016.
- Siliciano RF, Greene WC. HIV Latency. Cold Spring Harb Perspect Med. 2011 Sep; 1(1): a007096. Available at: www.ncbi.nlm.nih.gov/pmc/articles/PMC3234450/. Last accessed on October 30, 2016.
- Savarino A, Shytaj IL. Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology. 2015; 12: 51. Available at: www.ncbi.nlm.nih.gov/pmc/articles/PMC4472405/. Last accessed on October 30, 2016.
- Paredes R, López Benaldo de Quirós JC, Fernández-Cruz E, Clotet B, Lane HC. The Potential Role of Interleukin-2 in Patients with HIV Infection. AIDS Rev. 2002 Jan-Mar; 4(1): 36-40. Available at: www.aidsreviews.com/files/2002_04_1_036-040.pdf. Last accessed on October 30, 2016.
- Abrams D, Lévy Y, Losso MH, et al. Interleukin-2 Therapy in Patients with HIV Infection. N Engl J Med. 2009 Oct 15; 361(16): 1548-1559. Available at: www.ncbi.nlm.nih.gov/pmc/articles/PMC2869083/. Last accessed on October 30, 2016.
- Sued O, Ambrosioni J, Nicolás D, et al. Structured Treatment Interruptions and Low Doses of IL-2 in Patients with Primary HIV Infection. Inflammatory, Virological and Immunological Outcomes. PLoS One. 2015 Jul 17; 10(7): e0131651. Available at: http://journals.plos.org/plosone/article/asset?id=10.1371%2Fjournal.pone.0131651.PDF. Last accessed on October 30, 2016.
- 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 Jul 26; 16(11): 1479-87. Available at: www.ncbi.nlm.nih.gov/pubmed/12131185. Last accessed on October 30, 2016.
- 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. Available at: https://clinicaltrials.gov/ct2/show/NCT01013415. Last accessed on October 30, 2016.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on October 30, 2016.
- 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. Available at: https://clinicaltrials.gov/ct2/show/NCT00071890. Last accessed on October 30, 2016.
- Tavel JA. Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study. PLoS One. 2010; 5(2): e9334. Available at: www.ncbi.nlm.nih.gov/pmc/articles/PMC2826395/. Last accessed on October 30, 2016.
- 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. Available at: https://clinicaltrials.gov/ct2/show/study/NCT00110812. Last accessed on October 30, 2016.
- 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 Jul 15; 200(2): 206-15. Available at: http://jid.oxfordjournals.org/content/200/2/206.long. Last accessed on October 30, 2016.
- French National Agency for Research on AIDS and Viral Hepatitis. Study of the Immunological Efficacy of Using Subcutaneous Interleukin-2 (IL-2) in Antiretroviral Naïve 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. Available at: https://clinicaltrials.gov/show/NCT00120185. Last accessed on October 30, 2016.
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- 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 Mar 27; 26(6): 711-20. Available at: http://journals.lww.com/aidsonline/Fulltext/2012/03270/Effect_of_intermittent_interleukin_2_therapy_on.7.aspx. Last accessed on October 30, 2016.
- National Institutes of Health (NIH): News Release, dated February 10, 2009. IL-2 Immunotherapy Fails to Benefit HIV-Infected Individuals Already Taking Antiretrovirals. Available at: www.nih.gov/news-events/il-2-immunotherapy-fails-benefit-hiv-infected-individuals-already-taking-antiretrovirals. Last accessed on October 30, 2016.