Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Non-nucleoside analogs interfere with the life cycle of HIV by preventing the transcription of viral RNA into DNA. There is no "best" non-nucleoside. As of January 2008, the FDA-approved non-nucleosides include nevirapine, delavirdine, efavirenz, and etravirine. Because resistance develops rapidly when non-nucleosides are used alone, they should always be used with other antiretrovirals. Patients who are taking any type of antiretroviral drugs must be followed closely by a health care professional for treatment-related side effects.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) include the following:
- Efavirenz (Sustiva)
Efavirenz is the only non-nucleoside recommended by the U.S. Department of Health and Human Services to be used as a first-line treatment, with two nucleosides, in patients starting antiretroviral therapy. The usual dose is three 200 mg pills at bedtime, taken with or without food.
Side effects, which occur in about half of all patients who take this drug, include dizziness, poor concentration, confusion, abnormal dreams, depression, and drowsiness. These effects usually improve as therapy continues and typically last only about 2 to 4 weeks.
About 25 percent of adults and 40 percent of children who take efavirenz develop a skin rash within the first couple of weeks of treatment. The rash typically lasts about 2 weeks and is usually treatable. If the rash is severe, the drug should be discontinued.
Patients with a known or suspected history of hepatitis B or C should be monitored carefully while taking efavirenz. There appears to be an association, though not necessarily causal, between this drug and hepatitis. Due to a risk for birth defects, women who are pregnant or planning on becoming pregnant should not take efavirenz.
- Nevirapine (Viramune)
Nevirapine is especially effective for patients who have lower-than-average HIV viral loads before starting treatment. The usual dose is two 200 mg pills daily, taken both at once or at separate times during the day. Patients start dosage with a 2-week lead-in period of only 200 mg per day. The lead-in period reduces the likelihood of developing a skin rash, the most common side effect of nevirapine.
The skin rash, which develops in about 20–25 percent of all patients, usually occurs within the first 4 weeks of treatment. It is typically mild to moderate, but can be life threatening. About 25 percent of patients who develop rashes require hospitalization, although less than half of those who are hospitalized must discontinue nevirapine because of it. If a patient develops a skin rash, he or she should contact a physician or other health care professional immediately.
Nevirapine appears to be safe for women who are pregnant. Because the drug passes into breast milk, nevirapine decreases the risk for transmission of HIV from mother to infant.
- Delavirdine (Rescriptor)
Delavirdine boosts levels of the protease inhibitors in the blood. This is unusual, because the other two non-nucleoside drugs decrease blood levels and possibly the effectiveness of protease inhibitors. Delavirdine increases the levels of indinavir by 300 percent, levels of saquinavir by 200 percent, and levels of nelfinavir by 100 percent. These increases can be helpful in simplifying the dosage of protease inhibitors and overcoming viral resistance.
Rescriptor is approved for use in adults. The FDA-approved dose is 400 mg, three times a day, with or without food. The main side effect of delavirdine is a rash, which occurs in approximately 25 percent of the patients who take it. The rash is usually treatable and does not require stopping the drug. However, in some cases, the rash is severe and is accompanied by other symtoms (e.g., malaise, fever, muscle or joint pain, blisters, mouth sores, swelling). Patients who experience a serious reaction may need to discontinue taking this drug. Other side effects include headache, nausea, and fatigue.
- Etravirine (Intelence)
Etravirine was approved by the FDA in January 2008 to treat HIV infections that do not respond to other medications. This drug has not been studied in children under the age of 16 or in women who are pregnant. It is approved for use in adults and is used in combination with other medications.
Side effects of etravirine include nausea and rash. A serious skin reaction may occur in some patients. Long-term effects of this drug are unknown.