A New Once a Day Nucleoside
Emtriva: A New Option in Once Daily HIV Therapy
August 12, 2003
Emtriva (also known as FTC and Emtriva) is a new once-a-day nucleoside reverse transcriptase inhibitor (NRTI) that is used in combination with other antiretroviral medications by people with HIV infection. With the addition of Emtriva, there are now 4 NRTI medications that can be taken once daily: Videx EC (didanosine, ddI), Viread (tenofovir), Epivir (3TC).
Emtriva is very similar to Epivir in several ways. First, both medications are analogues of a nucleoside protein called cytosine. When HIV infects a cell, it requires certain chemical substances such as nucleosides in order to produce genetic material (DNA) to allow it to reproduce and make more HIV. Drugs such as Emtriva are able to 'trick' HIV because they are similar enough to the actual nucleoside. When HIV uses Emtriva instead of cytosine, the production of HIV genetic material is terminated. All NRTI medications mimic one nucleoside or another to inhibit HIV and prevent new HIV from being produced by the infected cell.
The ability of HIV to develop resistance to Emtriva and Epivir is also very similar. Certain mutations can occur in HIV that decreases the ability of antiretroviral medications to work. The types of changes that decrease the activity of Epivir also decrease the activity of Emtriva. Specifically, a mutation called M184V/I, is common to both Epivir and Emtriva and renders the virus able to resist both drugs. Changes in HIV that reduce the activity of other NTRI medications may also reduce the activity of Emtriva.
Studies have compared the activity of Emtriva to both Epivir and Zerit (d4T or stavudine). In comparing Emtriva given once daily to Epivir given twice daily, one study indicated that treatment with either Emtriva or Epivir in addition to other antiretroviral medications resulted in a similar response rate. In this study, an HIV viral load of less than 50 copies per mL was maintained for 48 weeks by 67% of the people taking the Emtriva-containing regimen and by 72% of the people taking the Epivir-containing regimen.
Another study compared a regimen of Videx and Sustiva (efavirenz) both given once daily with either Emtriva once daily or Zerit given twice daily. In this study, an HIV viral load of less than 50 copies per mL was maintained for 48 week by 78% of people taking the Emtriva-containing regimen and by 59% of the people taking the Zerit-containing regimen. This study was double-blinded, meaning everyone took pills twice daily.
A potential advantage that Emtriva has over Epivir is the amount of time that it is able to remain inside of cells. This is called the intracellular half-life or the amount of time for half of the drug to be cleared from inside the cell. Of the NRTI medications, Videx, Viread, and Emtriva have the longest intracellular half-lives. At this time, however, the clinical significance of the intracellular half-life upon treatment outcomes is unknown. The most common adverse events reported during clinical trials of Emtriva when used in combination with other antiretrovirals include the following: headache, nausea/vomiting, muscle weakness (asthenia), increased cough and runny nose (rhinitis).
Emtriva is not expected to have any serious drug interactions. Emtriva is eliminated through the kidneys and patients with decreased renal function will need to take a modified dose.
The FDA approved dose and indication for Emtriva is one 200mg capsule administered once daily with or without food for use in combination with other antiretroviral medications for the treatment of HIV-1 infection in adults. It is important to take all antiretroviral medications consistently at approximately the same time every day for the best possible outcomes.
With the addition of Emtriva, the number of convenient once-a-day HIV treatment options has expanded. Gilead Sciences, Inc., the company responsible for Emtriva and Viread, is currently studying the possibility of combining Emtriva and Viread into a single pill. A single pill for two drugs will simplify an anti-HIV regimen even more.
Jeffery A. Faris, Pharm.D. works at the University of Washington, Northwest AIDS Education and Training Center. For more information on the Center, visit their Web site at www.northwestaetc.org.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Ezine.