ChloroquineOther Names: Aralen, CQ, chloroquine phosphate Drug Class: Immune Modulators Molecular Formula: C18 H26 Cl N3 Registry Number: 54-05-7 (CAS) Chemical Name: Quinoline, 7-chloro-4-((4-(diethylamino)-1-methylbutyl)amino)- Chemical Class: 4-aminoquinoline Phase of Development: Chloroquine is in Phase II development for HIV.
(Compound details obtained from ChemIDplus Advanced,1 Retrovirology article,2 PLoS Medicine article,3 and ClinicalTrials.gov4)
What is an investigational drug?
Anis one that is under study and is not approved by the U.S. (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 What is an Investigational HIV Drug? fact sheet.
What is chloroquine?
Chloroquine is a drug that has been approved by FDA for the treatment ofand certain amoeba infections.5 It has also been studied as an investigational drug for HIV . As an HIV medicine, chloroquine is categorized as an immune modulator.2 Immune modulators (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function.
HIV infection can damage a person’sover the course of the viral infection. For example, HIV infection can make the immune system hyperactive. 2,6-9
Chloroquine may help calm an over-active immune system. This may help to reduce latent HIV reservoirs and increase CD4 counts. Ais 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. Latent HIV reservoirs are resting CD4 cells or other cells that are infected with HIV but not actively producing HIV in the body. Because HIV medicines do not work against HIV that's hidden in latent reservoirs, these reservoirs are one of the main obstacles to curing HIV infection. Researchers have studied whether chloroquine can help modify how the immune system functions as part of a strategy to treat or cure HIV infection.2,10
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.11
- 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.11
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase IIISome clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population. 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.11
In what phase of testing is chloroquine?
Chloroquine has been studied in Phase II clinical trials.4,12
What are some studies on chloroquine?
Study Name: ACTG A5258; NCT00819390
Status: This study has been completed.
Location: United States
- Group 1 participants were adults with HIV who had not taken HIV medicines for at least 6 months before starting the study. They had levels (the amount of HIV in a blood sample) of at least 1000 copies/mL and CD4 counts of at least 400 cells/mm3 within 30 days of starting the study.
- Group 2 participants were adults with HIV who had been receiving HIV medicines for at least 24 months before starting the study. They had viral loads of less than 200 copies/mL and CD4 counts of less than 350 cells/mm3 within 30 days of starting the study.
Purpose: The purpose of this study was to evaluate the safety and effectiveness of chloroquine in reducing immune system activation.4
Study Name: CTN 246; NCT02004314
Sponsor: CIHR Canadian HIV Trials Network
Phase: Not available
Status: This study has been completed.
Participants: Participants were adults with HIV who were on HIV medicines that suppressed their HIV. Participants had viral loads of less than 50 copies/mL for at least 36 weeks before the study and CD4 counts of 350 cells/mm3 or less.
Purpose: This study looked at the effect of chloroquine on CD4 counts and immune system activation in participants whose CD4 counts didn’t improve while they were taking HIV medicines even when their viral loads were suppressed.13
Study Name: NCT00308620
Sponsor: University of Minnesota - Clinical and Translational Science Institute
Status: This study has been completed.
Location: United States
Participants: Participants were adults with HIV who either had never taken HIV medicines before or had been off of HIV medicines for at least 16 months. Participants had viral load levels greater than 3000 copies/mL and CD4 counts greater than 250 cells/mm3.
Purpose: The purpose of this study was to see if chloroquine could reduce viral loads and immune system activation.10,14
For more details on the studies listed above, see the Health Professional version.
Other HIV-related studies of chloroquine have either been completed or are ongoing. A completed study (NCT00972725) looked at how a combination of a single of chloroquine and an investigational (F4/AS01β) affected the immune system of healthy adults. Chloroquine was used to increase an immune system response that was brought about by F4/AS01β.12,15
What side effects might chloroquine cause?
In the CTN 246 study (NCT02004314) discussed under the previous question, chloroquine was reported as being well tolerated by study participants. There were no serious side effects during the first week of treatment with chloroquine, but 1 participant stopped the study because of moderate digestive ( ) side effects.16
Additional information on side effects known to be associated with chloroquine can be found in the FDA-approved Chloroquine Full Prescribing Information.5
Because chloroquine is still being studied, information on possible side effects of the drug is not complete. As testing of chloroquine continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying chloroquine?
More information about chloroquine-related research studies is available from the AIDSinfo database of 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.
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.11
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/54-05-7. Last accessed on August 25, 2017.
- Savarino A, Shytaj IL. Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology. 2015; 12: 51. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472405/. Last accessed on August 25, 2017.
- Delves M, Plouffe D, Scheurer C, et al. The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites. PLoS Med. 2012 Feb; 9(2): e1001169. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283556/. Last accessed on August 25, 2017.
- AIDS Clinical Trials Group. A Phase II, Double Blind, Randomized, Exploratory Study of Chloroquine for Reducing HIV-Associated Immune Activation. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 8, 2009. NLM Identifier: NCT00819390. Available at: https://clinicaltrials.gov/ct2/show/NCT00819390. Last accessed on August 25, 2017.
- West-ward Pharmaceutical Corp. Chloroquine: full prescribing information, July 2010. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b585ad5-ae86-4403-b83f-8d8363d43da5. Last accessed on August 25, 2017.
- Barouch DH, Deeks SG. Immunologic Strategies for HIV-1 Remission and Eradication. Science. 2014 Jul 11; 345(6193): 169–174. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096716/. Last accessed on August 25, 2017.
- 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 August 25, 2017.
- Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother. 2001 May; 12(3): 133-50. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12959322. Last accessed on August 25, 2017.
- Siliciano RF, Greene WC. HIV Latency. Cold Spring Harb Perspect Med. 2011 Sep; 1(1): a007096. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234450/. Last accessed on August 25, 2017.
- Murray SM, Down CM, Boulware DR, et al. Reduction of Immune Activation with Chloroquine Therapy during Chronic HIV Infection. J Virol. 2010 Nov; 84(22): 12082–12086. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977889/. Last accessed on August 25, 2017.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: https://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on August 25, 2017.
- GlaxoSmithKline. A Study to Evaluate the Safety and Immunogenicity of a Booster Dose of GSK Biologicals' HIV Candidate Vaccine (732461) After Administration of Chloroquine in Healthy Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 3, 2009. NLM Identifier: NCT00972725. Available at: https://clinicaltrials.gov/ct2/show/study/NCT00972725. Last accessed on August 25, 2017.
- CIHR Canadian HIV Trials Network. Chloroquine as a Modulator of T Cell Immune Activation to Improve CD4 Recovery in HIV-infected Participants Receiving Antiretroviral Therapy: A Proof-of-concept Study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 27, 2013. NLM Identifier: NCT02004314. Available at: https://clinicaltrials.gov/ct2/show/NCT02004314. Last accessed on August 25, 2017.
- University of Minnesota - Clinical and Translational Science Institute. A Randomized, Pilot Study of the Anti-Viral and Anti-Inflammatory Effects of Chloroquine in Early HIV Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 27, 2006. NLM Identifier: NCT00308620. Available at: https://clinicaltrials.gov/ct2/show/study/NCT00308620. Last accessed on August 25, 2017.
- Leroux-Roels G, Bourguignon P, Willekens J, et al. Immunogenicity and Safety of a Booster Dose of an Investigational Adjuvanted Polyprotein HIV-1 Vaccine in Healthy Adults and Effect of Administration of Chloroquine. Clin Vaccine Immunol. 2014 Mar; 21(3): 302–311. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957681/. Last accessed on August 25, 2017.
- Routy JP, Angel JB, Patel M, et al. Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV-infected patients receiving antiretroviral therapy. HIV Med. 2015 Jan; 16(1): 48-56. Available at: http://onlinelibrary.wiley.com/doi/10.1111/hiv.12171/full. Last accessed on August 25, 2017.
Last Reviewed: August 25, 2017