The study of dexelvucitabine as a nucleoside reverse transcriptase inhibitor (NRTI) HIV medicine was discontinued in 2006. The company developing the drug announced that this decision was based on safety concerns in a Phase IIb long-term extension study in which dexelvucitabine was associated with a high incidence of severe hyperlipasemia. (Hyperlipasemia is a marker of pancreatic inflammation.)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.
To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.
Dexelvucitabine 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.
Dexelvucitabine is a prodrug, which means that it is an inactive drug. Once taken, a prodrug does not work until the body converts it into an active form. In the body, dexelvucitabine is converted to DFC-5′-triphosphate (DFC-TP).5,6
In vitro studies have shown that dexelvucitabine may be effective against strains of HIV that are no longer affected by other NRTIs. (In vitro studies are studies done in test tubes or other laboratory equipment and not on animals or humans).5
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.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
retrovirhttps://aidsinfo.nih.gov/drugs/385/elvucitabine/0/patient/ >elvucitabinee IIb study (known as Study 203), the safety and effectiveness of three different strengths of dexelvucitabine taken once daily were compared to that of placebo (an inactive drug that is identical in appearance to the active drug being studied). The study included HIV-infected participants who were already taking HIV medicines before entering the study (also called treatment-experienced). Participants had HIV mutations associated with drug resistance at the time they entered the study. For the first 2 weeks of the study, dexelvucitabine or placebo was added to a participant’s previous antiretroviral (ARV) therapy regimen. After 2 weeks, participants continued either dexelvucitabine or placebo and then also began an optimized background regimen. (An optimized background regimen is a combination of drugs, chosen on the basis of a person’s resistance test results and treatment history, that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant’s HIV infection.) During the final 8 weeks of the study, participants who had been receiving placebo were allowed to take dexelvucitabine.8,9
In this study, dexelvucitabine taken at the highest dose reduced viral load. (Viral load is the amount of HIV in a blood sample.) The study also found that treatment with the highest dose of dexelvucitabine and without the FDA-approved NRTIs lamivudine (brand name: Epivir) or emtricitabine (brand name: Emtriva) was more effective in reducing viral load than treatment with placebo. However, some participants taking dexelvucitabine did develop severe hyperlipasemia, which is high levels of lipase (a protein released by the pancreas) and which may indicate a problem with the pancreas. The majority of participants who had severe hyperlipasemia were also taking the FDA-approved NRTI didanosine (brand name: Videx). Pancreatitis (inflammation of the pancreas) also occurred in several participants.8,9
In a long-term extension of the study described above, dexelvucitabine taken at the two higher doses was further examined. During this study (known as Study 901), it became apparent that too many severe cases of hyperlipasemia were occurring in participants taking dexelvucitabine at the highest dose. Because of this safety issue, study investigators decided to stop the clinical development of dexelvucitabine for the treatment of HIV infection.4
elvucitabinease IIb study (Study 203) discussed under the previous question, most side effects were generally mild and included headache, fatigue, and gastrointestinal disorders. However, some participants (many of whom were also taking didanosine) developed severe hyperlipasemia and pancreatitis. Other serious side effects that may have been related to treatment included reduced number or function of red blood cells, reduced number of white blood cells, reduced number of platelets, and high levels of triglycerides.8
Severe hyperlipasemia was also reported in Study 901, the long-term extension of Study 203.4
If testing of dexelvucitabine continues, additional information on possible side effects will be gathered.
elvucitabinermation about dexelvucitabine-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.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.
Last Reviewed: November 19, 2014