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
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.
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.)
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.6
In most cases, an investigational drug must be proven safe and effective 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 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
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.
More information about lersivirine-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.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.
Last Reviewed: August 6, 2014