NOTE: The development of PSI-5004 for HIV treatment has been discontinued.
PSI-5004 is no longer being studied for use as an HIV medicine. 2008 appears to be the last time that PSI-5004 had an active clinical trial.5
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 PSI-5004?
PSI-5004 (also known as Racivir) is an investigational drug that was previously studied for the treatment of HIV infection.
PSI-5004 belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).2 NRTIs block an HIV enzyme called reverse transcriptase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.
PSI-5004’s chemical structure is similar to the structure of the FDA-approved NRTIs lamivudine (brand name: Epivir) and emtricitabine (brand name: Emtriva).6
In vitro studies have shown that PSI-5004 is also active against hepatitis B virus (HBV).6 (In vitro studies are studies done in test tubes or other laboratory equipment and not on animals or humans.)
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.7
- 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.7
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.7
(Some 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.)
In what phase of testing is PSI-5004?
PSI-5004 was studied in a Phase II clinical trial.2 The overall study of PSI-5004 as an HIV medicine has been discontinued.
What are some studies on PSI-5004?
Study Names: Study 101; NCT00040300
Location: Not available
- Participants were HIV-infected adult men who had never taken HIV medicines before starting the study.
- Participants had viral load levels greater than 5,000 copies/mL. (Viral load is the amount of HIV in a blood sample.)
- Participants had CD4 counts greater than 50 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.)
: This study was designed to evaluate the safety and drug properties of PSI-5004 and to find an effective dose
of the drug when used in combination with stavudine
(brand name: Zerit
) and efavirenz
(brand name: Sustiva
: Study 201; NCT00121979
: United States, Argentina, Mexico, Panama
- Participants were HIV-infected adults who had had no changes to their antiretroviral therapy (ART) regimen for at least 60 days before the start of the study. All participants were taking lamivudine as part of this regimen.
- Participants were on a failing ART regimen. (A failing ART regimen is one that is not effective at controlling a person's HIV.)
- All participants had HIV that contained a mutation called M184V. (The M184V HIV mutation is known to cause lamivudine to not work well.)
- Participants had viral load levels of at least 2,000 copies/mL and CD4 cell counts of at least 50 cells/mm3.
: The purpose of this study was to compare the safety and effectiveness of PSI-5004 to the safety and effectiveness of lamivudine
over 28 days.8,11
For more details on the studies listed above, see the Health Professional version
What side effects might PSI-5004 cause?
In the Phase Ib/IIa study (NCT00040300) discussed above, the most common side effects reported were mild to moderate dizziness and headache, both of which may have been related to PSI-5004. Some other side effects that may have been caused by PSI-5004 included difficulty concentrating, nausea, fatigue, common cold, and eye discomfort. Heartburn and vomiting were also noted by participants and may have been associated with PSI-5004.9,10
In the Phase II study (NCT00121979), no severe side effects were reported after 28 days of treatment with PSI-5004.12
If testing of PSI-5004 continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying PSI-5004?
More information about PSI-5004–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.
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.7
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: http://chem.sis.nlm.nih.gov/chemidplus/rn/143491-54-7. Last accessed on January 20, 2017.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on January 20, 2017.
- Hurwitz SJ, Otto MJ, Schinazi RF. Comparative pharmacokinetics of Racivir, (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine in rats, rabbits, dogs, monkeys and HIV-infected humans. Antivir Chem Chemother. 2005;16(2):117-27. Available at: http://www.intmedpress.com/serveFile.cfm?sUID=48452b2e-7c1d-49c7-9e79-7d04bd125fc2. Last accessed on January 20, 2017.
- Gilead Sciences, Inc.: Press Release, dated November 21, 2011. Gilead Sciences to Acquire Pharmasset, Inc. for $11 Billion. Available at: http://www.gilead.com/news/press-releases/2011/11/gilead-sciences-to-acquire-pharmasset-inc-for-11-billion. Last accessed on January 20, 2017.
- Clayden P, Collins S, Daniels C, et al. HIV i-BASE/Treatment Action Group. 2013 Pipeline Report. Benzacar A, ed. June 2013. Available at: http://www.treatmentactiongroup.org/sites/default/files/201306/2013%20Pipeline%20Report.pdf. Last accessed on January 20, 2017.
- Sen S, Mathur AG, Gupta RM, Kapila K, Chopra GS. Investigational Antiretroviral Drugs. Recent Pat Antiinfect Drug Discov. 2008 Nov;3(3):199-205. Available at: https://www.researchgate.net/profile/Sourav_Sen/publication/228361706_Investigational_Antiretroviral_Drugs/links/0fcfd50fd6511ebf44000000.pdf?origin=publication_list. Last accessed on January 20, 2017.
- 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 January 20, 2017.
- Pharmasset, Inc: Press Release, dated September 17, 2008. Racivir – New HIV Drug. Available from National AIDS Treatment Advocacy Project (NATAP) at: http://www.natap.org/2008/HIV/091708_01.htm. Last accessed on January 20, 2017.
- Herzmann C, Arastèh K, Murphy RL, et al. Safety, Pharmacokinetics, and Efficacy of (+/-)-β-2',3'-Dideoxy-5-Fluoro-3'-Thiacytidine with Efavirenz and Stavudine in Antiretroviral-Naïve Human Immunodeficiency Virus-Infected Patients. Antimicrob Agents Chemother. 2005 Jul;49(7):2828-33. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1168662/. Last accessed on January 20, 2017.
- Pharmasset. A 14-Day Study of Racivir When Used in Combination in HIV-Infected Males. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 24, 2002. NLM Identifier: NCT00040300. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00040300. Last accessed on January 20, 2017.
- Pharmasset. Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Exploring the Safety, Tolerability, and Antiviral Effect of Substituting 600 mg Racivir for 3TC in HIV-Infected Subjects Who Have the M184V Mutation and Are Currently Failing on a HAART Regimen Containing Lamivudine. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 18, 2005. NLM Identifier: NCT00121979. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00121979. Last accessed on January 20, 2017.
- Cahn P, Sosa N, Wiznia A, et al. Racivir Demonstrates Safety and Efficacy in Patients Harboring HIV with the M184V Mutation and <3 TAM. Abstract presented at: 14th Conference on Retroviruses and Opportunistic Infections (CROI); February 25-28, 2007; Los Angeles, CA. Abstract 488. Available at: http://www.retroconference.org/2007/Abstracts/30151.htm. Last accessed on May 29, 2013.
Last Reviewed: January 20, 2017