Other Names: Depakene, Depakote, Depakote ER, Epival, VPA, divalproex sodium, valproate
Drug Class: Latency-Reversing Agents
Molecular Formula: C8 H16 O2
Registry Number: 99-66-1 (CAS)
Chemical Name: 2-propylpentanoic acid
Chemical Class: Other Carboxylic Acid Derivatives
Organization: AbbVie Inc.; Abbott Laboratories
Phase of Development:
Valproic acid is in Phase II development as a latency-reversing agent for HIV.
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 Treatment Action Group website,3 and Depakote ER full prescribing information4)
What Is Valproic Acid?
Valproic acid is an investigational drug that is being studied as part of a strategy to cure HIV infection.5,6 Valproic acid is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of certain symptoms of bipolar disorder (a type of mental illness), the treatment of some types of seizures, and the prevention of migraine headaches.4
As an investigational therapy, valproic acid belongs to a group of HIV drugs called latency-reversing agents.3 There are different types of latency-reversing agents. Valproic acid is a type of latency-reversing agent called a histone deacetylase (HDAC) inhibitor.7
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.
How Do Latency-Reversing Agents Work?
Currently, there is no cure for HIV infection. One of the main obstacles to curing HIV infection is that the virus can remain hidden and inactive (latent) inside certain cells of the immune system (such as resting CD4 cells) for many months or even years. The cells where latent HIV hides are known as the latent HIV reservoir. Because HIV in this latent state is inactive, the immune system cannot detect the virus, and the antiretroviral (ARV) drugs that are used to treat HIV have no effect on it.8,9
Latency-reversing agents work by drawing HIV out of its latent state within resting CD4 cells. Once the latent HIV is reactivated, the CD4 cells that harbor the virus may more likely be recognized and killed by the body's immune system or may be killed by certain HIV therapies, such as those that can enhance the body's immune response to HIV. Researchers hope that combined use of valproic acid and other HIV-fighting strategies, including ongoing antiretroviral therapy (ART), may fully eliminate HIV from the body.7,9 To learn more, see the AIDSinfo What is a Latent HIV Reservoir? fact sheet.
Which Clinical Trials Are Studying Valproic Acid?
Study Names: CTN-205; NCT00289952
Status: This study has been completed.
Purpose: The purpose of this study was to determine whether valproic acid in combination with ART could reduce the amount of latent HIV.5,10
Study Name: NCT00614458
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to determine whether adding valproic acid and the HIV medicine raltegravir to a participant's current ART regimen could reduce the amount of latent HIV.6,11
Study Names: LUNA; NCT03525730
Status: This study is currently recruiting participants.
Purpose: The purpose of this study is to examine whether valproic acid along with pyrimethamine can reactivate latent HIV and reduce the amount of latent HIV.12
For more details on the studies listed above, see the Health Professional version of this drug summary.
What Side Effects Might Valproic Acid 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 valproic acid listed above.
In this Phase II study, some participants dropped out because of side effects they experienced when they were receiving valproic acid. As treatment time on valproic acid increased, the number of participants dropping out of the study also increased.5,10
In this Phase II study that looked at adding valproic acid and raltegravir to ART, no significant side effects related to valproic acid were reported.6,11
Because valproic acid is still being studied, information on possible side effects of the drug is not complete. As testing of valproic acid continues, additional information on possible side effects will be gathered.
Where Can I Get More Information About Clinical Trials Studying Valproic Acid?
More information about valproic acid-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.
- United States National Library of Medicine. ChemIDplus Advanced: valproic acid. https://chem.nlm.nih.gov/chemidplus/rn/99-66-1. Accessed September 11, 2018.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed September 11, 2018.
- Treatment Action Group website. Research toward a cure trials. www.treatmentactiongroup.org/cure/trials. Accessed September 11, 2018.
- AbbVie Inc. Depakote ER: full prescribing information. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dc024ce-efc8-4690-7cb5-639c728fccac. Accessed September 11, 2018.
- McGill University Health Center. Use of valproic acid to purge HIV from resting CD4+ memory cells: a proof-of-concept study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 8, 2006. NLM Identifier: NCT00289952. https://clinicaltrials.gov/ct2/show/NCT00289952. Accessed September 11, 2018.
- University of North Carolina, Chapel Hill. 10493 - MK-0518 intensification and HDAC inhibition in depletion of resting CD4+ T cell HIV infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 31, 2008. NLM Identifier: NCT00614458. https://clinicaltrials.gov/ct2/show/NCT00614458. Accessed September 11, 2018.
- Rasmussen TA, Tolstrup M, Winckelmann A, Østergaard L, Søgaard OS. Eliminating the latent HIV reservoir by reactivation strategies. Hum Vaccines Immunother. 2013;9(4):790-799.
- National Institute of Allergy and Infectious Diseases (NIAID). Bulletin: NIAID invites applications to conduct basic research on HIV persistence: studies key to search for a cure. https://wayback.archive-it.org/6721/20160908184013/http://www.niaid.nih.gov/news/newsreleases/Archive/2009/Pages/HIV_persistence.aspx. Accessed September 11, 2018.
- Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096.
- Routy JP, Tremblay CL, Angel JB, et al. Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Med. 13(5):291-296.
- Archin NM, Cheema M, Parker D, et al. Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoS ONE. 2010;5(2). www.ncbi.nlm.nih.gov/pmc/articles/PMC2826423/. Accessed September 11, 2018.
- Erasmus Medical Center. LRAs united as a novel anti-HIV strategy (LUNA): a randomized controlled trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 23, 2018. NLM Identifier: NCT03525730. https://clinicaltrials.gov/ct2/show/NCT03525730. Accessed September 11, 2018.
[Note from TheBody: This article was created by AIDSinfo, who last updated it on Sept. 11, 2018. We have cross-posted it with their permission.]