Taking the drug: The standard dose of Sustiva is 600 mg taken once a day. The general recommendation is to take the drug at bedtime. Sustiva can be taken with or without food. Taking Sustiva at the same time as eating a fatty meal is not recommended though, since the fat can cause drug levels in the body to get too high.

New Public Health Service HIV treatment guidelines say that the best way to use anti-HIV drugs is in three or four-drug combinations. The guidelines currently recommend the following combinations as first treatment for HIV:

• Two nucleoside analogs (AZT+3TC, d4T+3TC, d4T+ddI, AZT+ddI, or AZT+ddC) with one of the following: Crixivan, Fortovase, Norvir, Sustiva, Viracept or Norvir and Fortovase combined.
• If one of the above combinations cannot be used, an alternative is two nucleoside analogs (same combinations as listed above) with Viramune or Rescriptor.

Trial results: The major study of Sustiva compared treatment with AZT (Retrovir), 3TC (Epivir) and Sustiva to the widely used combination of AZT/3TC/Crixivan. Participants in this study hadn't taken 3TC, NNRTIs or protease inhibitors before. The study has now been going on for over a year. efavirenz (Sustiva).

Some researchers thought that an anti-HIV drug combination using an NNRTI drug like Sustiva would not work well in people with high viral loads. To answer this question, the researchers looked at what happened to people who began the study with viral loads of over 100,000 copies. Everyone in this group who took AZT/ 3TC/Sustiva had viral loads of less than 400 copies after 48 weeks, showing that the drug can work well even if the viral load is high.

Sustiva has also been studied in combination with protease inhibitors. For people who have already taken anti-HIV drugs and need a new combination, Sustiva will probably be used in combination with nucleoside analogs and protease inhibitors. Because Sustiva can affect the levels of protease inhibitors in the body, there are guidelines for each of the available protease inhibitors.

• indinavir (Crixivan): When combined with Sustiva, the dose of Crixivan should be increased to 1000 mg. every 8 hours.
• nelfinavir (Viracept): Sustiva increases Viracept levels slightly, but no dose adjustment is recommended.
• saquinavir (Fortovase): Sustiva greatly reduces the levels of Fortovase - these drugs should not should not should not should not should not be taken together until the correct dosing is worked out. An exception may be Sustiva combined with Fortovase and ritonavir (Norvir), since Norvir greatly increases Fortovase levels.
• ritonavir (Norvir): Sustiva does not significantly affect Norvir levels, and no dose adjustments are recommended.
• amprenavir (Agenerase): Sustiva reduces levels of this experimental protease inhibitor, and the correct dosing of this combination is under investigation.

Drug interactions: Be sure you talk to your doctor about other drug interactions, as many medications can interact with Sustiva and require a change in dose. The following drugs should not should not should not should not should not be taken with Sustiva: astemizole (Hismanal), midazolam (Versed), triazolam (Halcion), cisapride (Propulsid), and anti-migraine drugs known as ergot derivatives. Sustiva has been shown to reduce levels of methadone in the body. In a study of five people taking methadone maintenance and Sustiva, the methadone dose had to be increased an average of about 22mg to avoid symptoms of withdrawal.

Side effects: The major side effects from Sustiva are on the central nervous system, and include: dizziness, sleeplessness, intense dreams, altered mood and anxiety. These side effects are worst during the first two to four weeks of treatment. There have been reports of severe anxiety, depression and difficulty concentrating in people starting Sustiva. Anecdotal stories suggest that a few people may have become suicidal. Because of these problems, it's important that people starting this drug have someone to call if they experience mental problems and need support. It's also important to be careful about everyday or work-related tasks that require concentration, such as driving. Several Network members report having to take time off work when first starting Sustiva due to difficulty concentrating. Sustiva can also cause a rash. The rash is milder than with other NNRTIs, and usually goes away on its own. In one large study, about 1 in 4 people stopped taking Sustiva because of side effects.

Resistance: At the moment, researchers think Sustiva won't work very well against HIV that's become resistant to the other approved NNRTIs. It's also likely that virus that's resistant to Sustiva will be resistant to the other approved NNRTIs. Studies are ongoing.

The manufacturers of Sustiva, Dupont Pharma, have set up a patient assistance program for people having difficulty accessing the drug. Call (800) 334-4486 (800) 334-4486 (800) 334-4486 (800) 334-4486 (800) 334-4486 for more information.