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 AIDSinfo What is an Investigational HIV Drug? fact sheet.
What is poly-ICLC?
Poly-ICLC is an investigational drug that is being studied as part of a strategy to cure HIV infection.2
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.)5,6
Poly-ICLC belongs to a general class (group) of HIV drugs called latency-reversing agents. There are different types of latency-reversing agents. Poly-ICLC is a type of latency-reversing agent called a toll-like receptor agonist.2
How do latency-reversing agents work?
Latency-reversing agents 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.6,7
In addition, any new virus that is produced during reactivation can then be prevented from infecting other cells with the use of ongoing ART.6,7 Recent research has shown that additional therapies, together with latency-reversing agents, may be needed to fully eliminate latent HIV from the body.7
In addition to being a potential latency-reversing agent, poly-ICLC may also improve the body’s immune response to HIV.8
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.9
- 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.9
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.9
(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 poly-ICLC?
Poly-ICLC is currently being studied in a Phase I/II clinical trial.8
What are some studies on poly-ICLC?
Study Name: NCT02071095
Sponsor: Nina Bhardwaj
Location: United States
- Participants are HIV-infected adults who have had no changes to their ART regimen for at least 48 weeks.
- Participants have had viral load levels of less than 50 copies/mL for at least 48 weeks. (Viral load is the amount of HIV in a blood sample.)
- Participants have had CD4 counts of greater than 500 cells/mm3 within 30 days of the beginning of the study. (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.)
- A blood test shows evidence of virus activity inside participants’ cells.
: The purpose of this study is to evaluate poly-ICLC’s safety and to see whether poly-ICLC can reactivate latent HIV hiding inside cells and enhance immune responses in people with HIV. If poly-ICLC proves to be safe and effective, then investigators hope that poly-ICLC might be used to improve the body’s immune response to a therapeutic HIV vaccine
For more details on this study, see the Health Professional version
Other HIV-related clinical trials of poly-ICLC have been completed. In a Phase I study (NCT01127464
), researchers investigated poly-ICLC’s ability to increase the effectiveness of an investigational HIV vaccine called DCVax-001.10
What side effects might poly-ICLC cause?
In the Phase I/II study (NCT02071095) discussed under the previous question, early data showed that most side effects related to poly-ICLC were mild or moderate in severity. The most common side effects reported so far have been mild reactions where poly-ICLC was injected (called injection site reactions), such as pain and reddening of the skin. Other side effects include fever, chills, muscle aches, fatigue, headache, and a general feeling of illness.11
Because poly-ICLC is still being studied, information on possible side effects of the drug is not complete. As testing of poly-ICLC continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying poly-ICLC?
More information about research studies related to poly-ICLC 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.
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.9
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.nlm.nih.gov/chemidplus/rn/59789-29-6. Last accessed on November 9, 2016.
- Treatment Action Group website. Research Toward a Cure Trials. Available at: http://www.treatmentactiongroup.org/cure/trials. Last accessed on November 9, 2016.
- Wong JP, Nagata LP, Christopher ME, Salazar AM, Dale RM. Prophylaxis of acute respiratory virus infections using nucleic acid-based drugs. Vaccine. 2005 Mar 18; 23(17-18): 2266-8. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15755608. Last accessed on November 9, 2016.
- Oncovir, Inc. website. About Oncovir. Available at: http://www.oncovir.com/index.html. Last accessed on November 9, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID): Bulletin, dated June 16, 2009. NIAID Invites Applications to Conduct Basic Research on HIV Persistence: Studies Key to Search for a Cure. Available at: https://wayback.archive-it.org/6721/20160908184013/http://www.niaid.nih.gov/news/newsreleases/Archive/2009/Pages/HIV_persistence.aspx. Last accessed on November 9, 2016.
- Siliciano RF, Greene WC. HIV Latency. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a007096. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234450/. Last accessed on November 9, 2016.
- Rasmussen TA, Tolstrup M, Winckelmann A, Ostergaard L, Søgaard OS. Eliminating the latent HIV reservoir by reactivation strategies. Hum Vaccin Immunother. 2013 Apr 1;9(4):790-799. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903897/. Last accessed on November 9, 2016.
- Nina Bhardwaj. Simultaneous Disruption of Latency and Immune Enhancement by Poly-ICLC During HIV-1 Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 21, 2014. NLM Identifier: NCT02071095. Available at: https://clinicaltrials.gov/ct2/show/NCT02071095. Last accessed on November 9, 2016.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on November 9, 2016.
- Rockefeller University. A Randomized, Placebo-controlled, Dose-escalating, Double-blinded Phase I Study to Evaluate the Safety and Immunogenicity of Anti-DEC-205 Monoclonal Antibody (Mab) Targeted HIV Gag p24 Vaccine (DCVax-001) With Poly ICLC (Hiltonol) as Adjuvant in HIV-uninfected Healthy Volunteers. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 19, 2010. NLM Identifier: NCT01127464. Available at: https://clinicaltrials.gov/ct2/show/NCT01127464. Last accessed on November 9, 2016.
- Miller EA, Sabado R, Salazar A, LaMar M, Markowitz M, and Bhardwaj N. Poly-ICLC, a TLR Agonist, Is Safe and Tolerable in HIV-Infected Individuals. Paper presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, Massachusetts. Abstract 322. Available at: http://www.croiconference.org/sessions/poly-iclc-tlr-agonist-safe-and-tolerable-hiv-infected-individuals. Last accessed on November 9, 2016.
Last Reviewed: November 9, 2016