PI Perspective #36

October 2003     View PDF     En español

FTC (emtricitabine, Emtriva)

The FDA approved FTC (emtricitabine, Emtriva) in July 2003 for use by adults in combination with other anti-HIV drugs. FTC is a nucleoside analog reverse transcriptase inhibitor (NRTI). Other drugs in this class include 3TC, abacavir, AZT, Combivir, d4T, d4T XR, ddC, ddI, ddI EC and Trizivir.

Who should use it?
FTC is very similar to 3TC. Thus far it has shown relatively few side effects. The advantage of FTC’s once daily dosing may appeal to those trying to simplify their regimens.

What does the research show?
Several studies support the approval of FTC. One included 571 people who had never taken anti-HIV drugs. Volunteers received ddI and efavirenz with either FTC or d4T. After 48 weeks (nearly one year), 81% of those receiving FTC sustained undetectable viral loads compared to 68% on d4T. CD4+ cell counts increased about the same between the groups, though slightly higher for FTC recipients. More people on d4T quit the study because of side effects—22% on d4T vs. 15% on FTC.

In another study, 440 people used either FTC (once daily) or 3TC (twice daily) with other anti-HIV drugs. Before study entry, all were on effective, standard therapy including 3TC along with other anti-HIV drugs for at least 12 weeks. People stayed on their regimens but were randomly assigned to either continue on 3TC or switch to FTC. After 48 weeks, outcomes were similar. Side effects were fairly similar between the groups.

In general, results from these two large studies suggest that FTC may be slightly more active and have fewer side effects than d4T. FTC appears to have similar activity and with comparable side effects to 3TC.

How to use it?
FTC is a 200mg pill, taken once daily, with or without food. FTC’s once daily dosing makes it attractive to use. Dose changes are likely needed for people with kidney complications, including those on dialysis.

What about side effects?
FTC has relatively few side effects. The most common ones include headache, diarrhea, nausea and rash. Only 1% of volunteers quit the studies due to these side effects. Generally speaking, the levels of side effects were similar with FTC as with other regimens, such as those using d4T or 3TC. A noted exception was skin discoloration of the palms of hands and/or soles of feet among those on FTC. There were no other symptoms related to this discoloration, and researchers aren’t sure what is causing this side effect.

In addition to being active against HIV, FTC appears to be active against hepatitis B virus (HBV). People with both HIV and HBV have faced a worsening of HBV-related complications after stopping FTC. For this reason, it’s recommended that people living with both use caution when taking FTC, as it has not been tested well in this setting. Moreover, careful monitoring of HBV should follow after stopping FTC.

A relatively rare but serious side effect from using NRTIs is severe chemical imbalances in the body called lactic acidosis. For more information on lactic acidosis, read Project Inform’s publication, Mitochondrial Toxicity, as well as new information on ddI and d4T in PI Perspective #35. Also, the use of anti-HIV drugs have been linked to changes in body shape and fat distribution. NRTIs may be particularly associated with loss of fat, such as facial or limb wasting. For more information, read Project Inform’s publication, Lipodystrophy Syndrome(s).

What about resistance?
Resistance to a drug occurs when the virus changes or modifies itself such that it is no longer crippled in its replication cycle by the effects of a drug. Resistance to FTC may be slow to develop when used with other anti-HIV drugs. However, HIV resistance to FTC has been seen.

Cross-resistance is when resistance to one drug also causes resistance to other drugs. Studies suggest that once HIV has developed resistance to FTC, then 3TC and ddC may be less effective. FTC and 3TC share similar resistance patterns, so virus resistant to 3TC will likely be resistant to FTC as well. Test tube studies suggest that HIV showing certain types of resistance to abacavir, ddI, tenofovir or ddC may also be less susceptible to FTC.

Are there concerns about drug interactions?
It’s not expected that FTC will have many drug interactions. Studies have been conducted with a few other anti-HIV drugs and no interactions were observed. Whether or not FTC interacts with other medications (methadone, psychiatric medicines, street drugs, etc.) is not known. There are possible interactions with other drugs that are cleared through the kidneys. People are encouraged to discuss these interactions between ALL of the therapies and substances they are taking with their doctor and/or pharmacist.

Discussion
Some consider FTC to be a “me too” NRTI: just another drug in a growing list with no special benefits. Data suggesting that FTC is superior to d4T may have been important a year or so ago when d4T was among the most used and seemingly favored NRTI among patients and providers. However, the use of d4T has waned because of its implicated role in fat loss and liver complications.

How FTC compares to 3TC is perhaps more important. 3TC has long been regarded as one of the most potent NRTIs when used correctly with other potent drugs. The arrival of Combivir as a single pill, taken twice daily, made three-drug therapy immensely easier. Combivir provided two NRTIs as the backbone for a potent three-drug regimen. Doctors and patients alike sighed in relief at the new formulation that helped ease the pill burden and improve adherence

Ultimately the question is what does FTC add to the anti-HIV arsenal? It appears to be a fairly potent NRTI and similar in many ways to 3TC. Like 3TC, it has relatively few side effects (though slightly more than 3TC). One nice advantage is that FTC is taken just once daily. This benefit may be less critical now that more and more drugs are coming out in once daily formulations, however.

Gilead Sciences, who developed FTC, also makes another anti-HIV drug called tenofovir. It is also taken once daily. It is Gilead’s goal to make them into a single pill taken once daily, allowing for a potent combination in one pill. With the new protease inhibitor atazanavir (also dosed once daily) and other advances on the horizon, it may soon be possible to construct potent three-drug regimens that need as few as one or two pills once daily.

FTC thus represents a sort of dawning of a new and important phase of refinement in HIV treatment—that is, drugs that are easier to take with fewer side effects and good potency. In and of itself, it offers very little in the short-term. Its real benefits likely won’t be realized until it’s co-formulated with tenofovir. The company hopes to launch this new pill in 2005.

Buying and Access
Emtricitabine is available by prescription. Some states may cover emtricitabine through their AIDS Drug Assistance Programs (ADAP). For information on your state ADAP eligibility and to find out if emtricitabine is covered, contact Project Inform’s toll-free Hotline at 1-800-822-7422. Information is also available through the AIDS Treatment Data Network at 1-800-734-7104 or www.atdn.org. People who lack insurance, Medicaid, ADAP coverage or cannot afford to pay for the drug can sometimes gain free access to them through the manufacturer’s Patient Assistance Program.

Emtricitabine: 800-445-3235

Bottom line on emtricitabine

• This NRTI appears similar to 3TC (lamivudine, Epivir), but requires only once-daily dosing and resistance may be less likely to develop to FTC.
• More studies are needed to identify the true value and role of FTC.

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