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AIDSinfo Drug Database

AIDSinfo Drug Database

Drugs by class



Lersivirine  Audio icon

Other Names: LRV, UK-453,061
Drug Class: Non-nucleoside Reverse Transcriptase Inhibitors
Molecular Formula: C17 H18 N4 O2
Registry Number: 473921-12-9 (CAS)
Chemical Name: 5-[3,5-diethyl-1-(2-hydroxyethyl)pyrazol-4-yl]oxybenzene-1,3-dicarbonitrile
Company: ViiV Healthcare
Phase of Development: Phase IIb (discontinued)

Chemical Image:
Click image to enlarge
Molecular Weight: 310.3552
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 ViiV Healthcare website,3 and Expert Opinion on Investigational Drugs article4)

NOTE: The development of lersivirine for HIV treatment has been discontinued.

The study of lersivirine as a non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV medicine was discontinued in 2013. The company developing the drug decided that lersivirine would not provide an improvement over currently approved HIV medicines already in use.4

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 lersivirine?

Lersivirine is an investigational drug that was studied for the treatment of HIV infection

Lersivirine belongs to a class (group) of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).2 NNRTIs attach to and 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, NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.

In vitro, lersivirine appears to work on certain HIV strains against which other NNRTIs no longer work.5 (In vitro refers to 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.6

  • 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.6

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.6


In what phase of testing is lersivirine?

Lersivirine has been studied in Phase IIb clinical trials.2 The development of lersivirine for the treatment of HIV infection was discontinued in 2013.4

What are some studies on lersivirine?

In a Phase IIb study (known as Study A5271015), two different doses of lersivirine taken once daily were compared to the FDA-approved NNRTI efavirenz (brand name: Sustiva) taken once daily in HIV-infected participants. The participants had never taken HIV medicines before entering the study (treatment-naive). Study participants, whether given lersivirine or efavirenz, also received other HIV medicines as part of their background regimens. (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are being given to help control a participant’s HIV infection.)7 

In this study, both doses of lersivirine proved as effective as efavirenz. In terms of safety, lersivirine and efavirenz had differences. Fewer severe side effects and fewer incidents of rash occurred with the use of lersivirine than with the use of efavirenz. The most common side effects that occurred in patients taking lersivirine were nausea and headache.7

In another Phase IIb study (known as Study A5271022), two different doses of lersivirine taken once daily were compared to the FDA-approved NNRTI etravirine (brand name: Intelence) taken twice daily in HIV-infected participants who had previously taken HIV medicines before (called treatment-experienced). Participants enrolled in this study had HIV with NNRTI resistance mutations. (NNRTI resistance mutations are genetic changes in HIV that cause the virus to become resistant to one or more HIV medicines in the NNRTI drug class. This means that certain NNRTI HIV medicines are no longer effective at controlling the person’s HIV.) All participants also received a background regimen consisting of one nucleoside reverse transcriptase inhibitor (NRTI) plus the FDA-approved protease inhibitors darunavir (brand name: Prezista) and ritonavir (brand name: Norvir). After 24 weeks of treatment, lersivirine was found to not be effective when compared to etravirine. For this reason, Study A5271022 was stopped early. The study was not stopped because of any safety concerns.8


What side effects might lersivirine cause?

In Study A5271015 discussed under the previous question, the most common side effects associated with lersivirine use after 48 weeks of treatment were nausea and headache. Rash was also reported, but it was not a common occurrence associated with lersivirine.7

If testing of lersivirine begins again, additional information on possible side effects will be gathered.

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

More information about lersivirine-related research studies is available from the AIDSinfo database of study summaries. Click on the title of any trial in the list to see the 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.6

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.


  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: Last accessed on August 6, 2014.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: Last accessed on August 6, 2014.
  3. ViiV Healthcare website. Quick Search for lersivirine. Available at: Last accessed on August 6, 2014.
  4. Platten M, Fätkenheuer G. Lersivirine - a new drug for HIV infection therapy. Expert Opin Investig Drugs. 2013 Dec;22(12):1687-94. Available at: Last accessed on August 6, 2014.
  5. Corbau R, Mori J, Phillips C, et al. Lersivirine, a Nonnucleoside Reverse Transcriptase Inhibitor with Activity against Drug-Resistant Human Immunodeficiency Virus Type 1. Antimicrob Agents Chemother. 2010 Oct;54(10):4451-63. Available at: Last accessed on August 6, 2014.
  6. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: Last accessed on August 6, 2014.
  7. Vernazza P, Wang C, Pozniak A, et al. Efficacy and safety of lersivirine (UK-453,061) vs. efavirenz in antiretroviral treatment-naïve HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicentre, randomised, double-blind, phase IIb trial (study A5271015). Abstract presented at: 6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome, Italy. Abstract TUAB0101. Available at: Last accessed on August 6, 2014.
  8. Pfizer. A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1. In: Bethesda (MD): National Library of Medicine (US). Registered on January 15, 2009. NLM Identifier: NCT00823979. Available at: Last accessed on August 6, 2014.

Last Reviewed: October 2, 2015

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