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.
Valproic acid is a drug that has been approved by FDA for the treatment of certain symptoms of bipolar disorder (a type of mental illness), the treatment of seizures, and the prevention of migraine headaches.3 It has been studied to see if it could be effective as part of a strategy to cure HIV infection.4,5
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 T cells) for many months or even years. While HIV is in this latent state, the immune system cannot recognize the virus, and antiretroviral therapy (ART) has no effect on it. (ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from replicating.)6-8
Valproic acid belongs to a class (group) of HIV drugs called histone deacetylase (HDAC) inhibitors.2 HDAC inhibitors reactivate (turn back on) latent HIV within resting CD4 T cells.8,9
HDAC inhibitors reactivate (turn back on) latent HIV within resting CD4 T cells. When latent HIV is reactivated, it is once again able to produce new virus and multiply (replicate). It is hoped that after latent HIV is reactivated, the CD4 T cells in which the virus was hiding are more likely to die off on their own or be recognized and killed by the body’s immune system.8,9
In addition, any new virus that is produced during reactivation can then be prevented from infecting other cells with the use of ongoing ART.8,9 Recent research has shown that additional therapies, together with HDAC inhibitors, may be needed to fully eliminate latent HIV from the body.9
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.10
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.10
The use of valproic acid to reduce latent HIV has been studied in Phase II clinical trials.2
Study Name: NCT00289952; CTN-205
Location: Canada (British Columbia, Ontario, and Quebec)
Participants: HIV-infected adults who were on antiretroviral therapy (ART) and who had a viral load (the amount of HIV in the blood) that was suppressed to less than 50 copies/mL for at least 1 year before starting the study. Participants had a CD4 count of at least 200 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function. The CD4 count of a healthy person ranges from 500 to 1,600 cells/mm3.)
Purpose: The purpose of this study was to determine whether valproic acid in combination with ART could reduce the amount of latent HIV in resting CD4 T cells.
Study Design: Fifty-six HIV-infected participants were assigned to one of the following two groups:
Study Name: NCT00614458
Location: United States (North Carolina)
Participants: HIV-infected adults who were on ART and who had a suppressed viral load of less than 50 copies/mL for at least 6 months before starting the study. Participants had a CD4 count of at least 300 cells/mm3.
Purpose: The purpose of this study was to determine whether adding valproic acid and the HIV medicine raltegravir to participants’ current ART regimen could reduce the amount of latent HIV in participants’ resting CD4 T cells.
Study Design: Six participants received raltegravir twice daily plus valproic acid twice daily, in addition to their current ART regimen.
During the study that looked at adding valproic acid to ART (NCT00289952), some participants dropped out of the study 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.12
During the study that looked at adding valproic acid and raltegravir to ART (NCT0064458), no significant side effects related to valproic acid were reported.13
Information on possible side effects of the drug is not complete. If testing of valproic acid continues, additional information on possible side effects will be gathered.
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.
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.10
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.
Last Reviewed: July 31, 2015