Drugs

Hydroxychloroquine

Hydroxychloroquine

Other Names: HCQ, Plaquenil, hydroxychloroquine sulfate Drug Class: Immune Modulators Molecular Formula: C18 H26 Cl N3 O Registry Number: 118-42-3 (CAS) Chemical Name: Ethanol, 2-((4-((7-chloro-4-quinolinyl)amino)pentyl)ethylamino)- Chemical Class: 4-aminoquinoline Phase of Development: Hydroxychloroquine is in Phase II development as an immune modulator for HIV treatment.

(Compound details obtained from ChemIDplus Advanced,1 Blood article,2 HIV i-BASE/Treatment Action Group 2015 Pipeline Report,3 PLoS Medicine article,4 and ClinicalTrials.gov5,6)

What is hydroxychloroquine?

What is hydroxychloroquine?

Hydroxychloroquine is an investigational drug that is categorized as an immune modulator.2 Immune modulators (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function.

To learn how investigational drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Hydroxychloroquine has also been approved by the Food and Drug Administration (FDA) for the treatment of malaria, lupus, and rheumatoid arthritis.7

HIV infection can cause a person’s immune system to become overactive (called immune hyperactivation). Immune hyperactivation can damage the immune system and cause HIV to progress faster.8–13 Hydroxychloroquine may be able to reduce immune hyperactivation.8,9

Which clinical trials are studying hydroxychloroquine?

Which clinical trials are studying hydroxychloroquine?

Study Names: 1) SEARCH 019; NCT02475915, and 2) SEARCH 026; NCT02470351
Phase: I/II
Status: These studies have been completed.
Location: Thailand
Purpose: The purpose of SEARCH 019 was to see how safely and effectively a combination of ART, vorinostat, hydroxychloroquine, and maraviroc controlled participants’ viral loads during a planned break from HIV medicines that followed the combination treatment. The researchers compared the combination treatment to ART alone. SEARCH 026 was a substudy that evaluated the effect of vorinostat, hydroxychloroquine, and maraviroc on the brains and spinal cords of participants in SEARCH 019.5,14,15

Study Names: HCQ-01; NCT01067417
Phase: II
Status: This study has been completed.
Location: United Kingdom
Purpose: The purpose of this study was to determine whether hydroxychloroquine could reduce immune hyperactivation and slow the decline of CD4 cell counts in participants who were not receiving ART.6,8

Study Name: 2009-012499-28 (EudraCT)
Phase: Not available
Status: This study has been completed.
Location: Italy
Purpose: The purpose of this study was to determine whether hydroxychloroquine in combination with ART could reduce immune hyperactivation and increase CD4 cell counts in people whose CD4 counts didn’t improve on ART alone, even when their viral loads were suppressed.2

For more details on the studies listed above, see the Health Professional version of this drug summary.

Other HIV-related studies evaluating hydroxychloroquine have been completed or are ongoing. One study (NCT02079077) looked at whether aspirin or hydroxycholoroquine could reduce immune hyperactivation in women who were not infected with HIV.16,17

What side effects might hydroxychloroquine cause?

What side effects might hydroxychloroquine cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in the studies of hydroxychloroquine listed above.

SEARCH 019 (NCT02475915); SEARCH 026 (NCT02470351):
In the SEARCH 019 study, two out of 10 people who received the combination of ART, vorinostat, hydroxychloroquine, and maraviroc experienced serious side effects. One of these participants dropped out of the study due to kidney problems and low levels of platelets (a type of blood cell) caused by the treatment. The other participant had diarrhea, which may have been caused by food poisoning. All of the study participants experienced nonserious side effects, but only people receiving the combination of ART, vorinostat, hydroxychloroquine, and maraviroc had low platelet counts and elevated creatinine levels (which are sometimes a sign of kidney problems).5,18 No long-term side effects were reported in the SEARCH 026 substudy by participants taking the combination treatment.14,19

HCQ-01 (NCT01067417):
In this study, there were no reported serious side effects related to hydroxychloroquine. Most of the side effects that occurred during the study were mild in severity. Flu-like illness and upper respiratory tract infections occured more often in participants who received hydroxychloroquine than in participants who received placebo. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)6,8

2009-012499-28 (EudraCT):
In the EudraCT (2009-012499-28) study, hydroxychloroquine was reported as well tolerated in all participants, except for one participant who experienced skin rash.2

Additional information on side effects known to be associated with hydroxychloroquine can be found in the FDA-approved Full Prescribing Information for Plaquenil.

Because hydroxychloroquine is still being studied, information on possible side effects of the drug is not complete. As testing of hydroxychloroquine continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying hydroxychloroquine?

Where can I get more information about clinical trials studying hydroxychloroquine?

More information about hydroxychloroquine-related research studies is available from the AIDSinfo 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.

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 information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: Hydroxychloroquine. https://chem.nlm.nih.gov/chemidplus/rn/118-42-3. Accessed December 27, 2018.
  2. Piconi S, Parisotto S, Rizzardini G, et al. Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders. Blood. 2011;118(12):3263-3272.
  3. Clayden P, Collins S, Frick M, et al. HIV i-BASE/Treatment Action Group. 2015 pipeline report. Benzacar A, ed. July 2015. http://www.pipelinereport.org/sites/default/files/201509/2015%20Pipeline%20Report%20Full.pdf. Accessed December 27, 2018.
  4. 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;9(2):e1001169.
  5. South East Asia Research Collaboration with Hawaii. A randomized study to compare the efficacy of vorinostat/hydroxychloroquine/maraviroc (VHM) in controlling HIV after treatment interruption in subjects who initiated ART during acute HIV infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 3, 2015. NLM Identifier: NCT02475915. https://clinicaltrials.gov/ct2/show/NCT02475915. Accessed December 27, 2018.
  6. Medical Research Council. Evaluation of the efficacy of hydroxychloroquine in decreasing immune activation in asymptomatic HIV-infected patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 10, 2010. NLM Identifier: NCT01067417. https://clinicaltrials.gov/ct2/show/NCT01067417. Accessed December 27, 2018.
  7. Concordia Pharmaceuticals Inc. Plaquenil: full prescribing information, May 2017. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34496b43-05a2-45fb-a769-52b12e099341. Accessed December 27, 2018.
  8. Paton N, Goodall R, Dunn D, et al. Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy a randomized controlled trial. JAMA J Am Med Assoc. 2012;308(4).
  9. Savarino A, Shytaj IL. Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology. 2015;12:51.
  10. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1).
  11. Barouch DH, Deeks SG. Immunologic strategies for HIV-1 remission and eradication. Science. 2014;345(6193):169–174.
  12. 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. http://hivinsite.ucsf.edu/InSite?page=kb-00&doc=kb-02-01-04. Accessed December 27, 2018.
  13. Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother. 2001;12(3):133-150.
  14. South East Asia Research Collaboration with Hawaii. Study SEARCH 026Assessment of the HIV CNS reservoir, neurological and neuro-cognitive effects, and source of rebound HIV in CNS in subjects participating in Study SEARCH 019. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 2, 2015. NLM Identifier: NCT02470351. https://clinicaltrials.gov/ct2/show/NCT02470351. Accessed December 27, 2018.
  15. Kroon E, Ananworanich J, Eubanks K, et al. Effect of vorinostat, hydroxychloroquine and maraviroc combination therapy on viremia following treatment interruption in individuals initiating ART during acute HIV infection. Abstract presented at: 21st International AIDS Conference (AIDS 2016); July 18-22, 2016; Durban, South Africa. Abstract TUAX0101LB. http://programme.aids2016.org/Abstract/Abstract/10535. Accessed December 27, 2018.
  16. University of Manitoba. Limiting HIV target cells by inducing immune quiescence in the female genital tract. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 3, 2014. NLM Identifier: NCT02079077.
  17. https://clinicaltrials.gov/ct2/show/NCT02079077. Accessed December 27, 2018.
  18. Fowke KR, Mwangi L, Boily-Larouche G, et al. Can we prevent HIV infection by focusing on the HIV target cell rather than the virus? Abstract presented at: HIV Research for Prevention; October 17-21, 2016; Chicago, Illinois. Abstract P19.25. https://web.archive.org/web/20170709195455/hivr4p.org/images/HIVR4P_2016_Abstract_Book.pdf. Accessed December 27, 2018.
  19. Kroon E, Ananworanich J, Eubanks K, et al. Effect of vorinostat, hydroxychloroquine and maraviroc combination therapy on viremia following treatment interruption in individuals treated during acute HIV infection. 21st International AIDS Conference (AIDS 2016); July 18-22, 2016; Durban, South Africa. Mascolini: Vorinostat, HCQ, Maraviroc Do Not Delay Time to Rebound After Interruption. Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2016. http://www.natap.org/2016/IAC/IAC_07.htm. Accessed December 27, 2018.
  20. Kroon E, Ananworanich J, Le LT, et al. Central nervous system impact of vorinostat, hydroxychloroquine and maraviroc combination therapy followed by treatment interruption in individuals treated during acute HIV infection (SEARCH 026). Poster presented at: 21st International AIDS Conference (AIDS 2016); July 18-22, 2016; Durban, South Africa. Poster LBPE005. http://programme.aids2016.org/PAGMaterial/eposters/0_10588.pdf. Accessed December 27, 2018.

Last Reviewed: January 4, 2019