AIDS Committee of Windsor: HIV Treatment Information

Summary
Efavirenz is a type of anti-HIV drug called a non-nucleoside reverse transcriptase inhibitor. Efavirenz can cause nervous-system side effects like dizziness, trouble sleeping, and trouble concentrating. Efavirenz can be taken once or twice a day, with or without food.

What is efavirenz?
Efavirenz, sold under the brand name Sustiva, is a type of antiretroviral drug called a non-nucleoside reverse transcriptase inhibitor. Antiretroviral drugs fight HIV infection by interfering with the life cycle of the virus. At each stage of this cycle, chemicals called enzymes help the virus make copies of itself (replicate). Some drugs can inhibit (slow down or stop) the actions of these enzymes. When these enzymes can't perform effectively, the virus does not replicate as efficiently, thus slowing the progression of HIV disease.

How does efavirenz work?
HIV infects cells and then replicates with the help of its own enzymes. In the first stage of replication, the enzyme reverse transcriptase converts the genetic material of the virus (RNA) to match the genetic material of the cell (DNA). Non-nucleoside reverse transcriptase inhibitors (NNRTIs or "non-nukes") like efavirenz interfere directly with the action of the reverse transcriptase enzyme, preventing it from working properly.

Combination therapy
For many people, combination therapy with three or more anti-HIV drugs can improve CD4+ counts and viral load measures as well as reduce opportunistic infections. Clinical trials have compared efavirenz + AZT + 3TC to the well-studied combination AZT + 3TC + indinavir. After 48 weeks, the efavirenz combination was at least as effective in lowering viral load and raising CD4+ counts as the indinavir combination.

Resistance and cross-resistance
Over time, as HIV makes copies of itself, the virus can change its structure. These changes allow HIV to resist the effects of antiretroviral drugs. Resistance to non-nukes, when used alone, appears as early as two weeks after treatment begins. Combining efavirenz with at least two other drugs may delay the development of drug resistance. To limit the risk of resistance, all anti-HIV drugs should be taken every day, exactly as prescribed. This strict schedule is necessary because resistant virus can develop if the level of drug in the blood drops. This may happen if doses are delayed or skipped.
It's generally believed that all non-nukes may be cross-resistant. This means that, if HIV becomes resistant to one brand of non-nuke, it will also resist the effects of other drugs in that class. In other words, if the virus has become resistant to efavirenz, it will probably be resistant to delavirdine and nevirapine.

Side effects
Over 50% of participants in efavirenz trials reported nervous-system side effects such as dizziness, trouble sleeping, drowsiness, trouble concentrating, and vivid dreams. These effects are strongest during the first two to four weeks on efavirenz. They usually get milder after about a month, and often go away on their own. If these side effects are troublesome, the dose can be divided in half and taken twice a day.

There may be more serious side effects that affect mood and the ability to think clearly.

Like other non-nukes, efavirenz can cause a skin rash. Often this will go away without treatment but it can be serious in some people. Anyone who develops a rash should contact their doctor as soon as possible. If the rash is severe or there are other symptoms like malaise, fever, blisters, sores in the mouth, itchy eyes, swelling, or muscle or joint pains, efavirenz must be stopped, and a doctor contacted immediately.

To date, there are no reports of side effects unique to women. However, pregnant women should not take efavirenz, because it caused birth defects in animal tests.

Drug interactions
Efavirenz is metabolized (broken down and processed) by the liver through the actions of the p450 cytochrome enzymes. Taking efavirenz with drugs that are metabolized the same way may change blood levels of each drug. As a result of these drug interactions, blood levels of some drugs may drop too low to be of benefit, or they may rise so high they cause serious side effects. Dosages of other drugs may therefore have to be raised or lowered, or some drugs may have to be changed.

The following drugs should not be used with efavirenz: cisapride (Prepulsid), triazolam (Halcion), midazolam (Versed), migraine drugs that are ergot derivatives (such as Cafergot, Ergodryl, Gravergol), and the antihistamines terfenadine (Seldane) and astemizole (Hismanal). If you're starting a new drug, check with your doctor or pharmacist about potential interactions with efavirenz.

Efavirenz and protease inhibitors
Indinavir (Crixivan): Because efavirenz lowers the amount of indinavir in the blood, the indinavir dose should be increased to 1,000 milligrams (mg) taken every eight hours for those on the combination.

Nelfinavir (Viracept): Efavirenz slightly raises the amount of nelfinavir in the blood, but a change in dose is not necessary.

Saquinavir (Fortovase): Efavirenz greatly reduces the amount of saquinavir in the blood. These drugs should not be used together.

Ritonavir (Norvir): No change in dose is necessary.

Amprenavir (Agenerase): Efavirenz lowers the amount of amprenavir in the blood. This combination should be avoided.

Dosage
The usual dose of efavirenz is 600 mg taken once a day. The manufacturer recommends taking efavirenz at bedtime because of its side effects, which can include drowsiness, dizziness and vivid dreams. If the side effects are too bothersome, the dose can be split into 300 mg taken twice daily. Efavirenz can be taken with or without food but it should not be taken with a high fat meal. Fatty food may increase efavirenz absorption, thus increasing the risk of side effects.

Availability
Efavirenz received marketing approval in March 1999. Provincial drug plans coverage may not be in place in all provinces.

This information was provided by the Community AIDS Treatment Information Exchange (CATIE). For more information, contact CATIE at 1-800-263-1638.