Drug studies are a very active area of HIV/AIDS research

Nucleoside reverse transcriptase inhibitors (NRTIs)

Nucleoside reverse transcriptase inhibitors, also called nucleoside analogs or nucleosides, interfere with the life cycle of HIV by preventing the transcription of viral RNA into DNA.

Most 3- and 4-drug regimens involve 2 nucleoside analogs, chosen on the basis of convenience, potential side effects, and patient preference. Certain drugs should not be used together because of the way they interact. For example, idovudine and stavudine should not be used together, and zalcitabine should not be combined with didanosine, stavudine, or lamivudine.

Drug studies are a very active area of HIV/AIDS research, and information is updated continually. It is important for patients to find a health care provider who specializes in HIV/AIDS medicine and knows about current clinical studies. Patients who are on antiretroviral therapy must be followed closely for treatment of related side effects.

Nucleosides can cause lactic acidosis (severely elevated blood lactate level) and liver enlargement (hepatomegaly; a rare but very serious side effect that can result in death). Lactic acidosis occurs more often in women and causes fatigue, belly pain, and shortness of breath. Nucleosides should be used with caution in patients who are at risk for liver disease, and treatment should be stopped if there is any indication of lactic acidosis or liver damage. Obesity increases the risk for side effects.

In most cases, nucleosides are combined with one other nucleoside plus either a non-nucleoside or protease inhibitor. NRTIs include the following:

• Zidovudine, azidothymidine (AZT, ZDV; Retrovir®)
  This medication was the first FDA-approved antiretroviral drug and was the first ray of hope in the AIDS epidemic. A pivotal 1987 study showed how 6 months of AZT treatment could dramatically decrease AIDS deaths.

Initially, AZT was used alone. Today, like all nucleosides, AZT is used with 2 or more other antiretroviral medications. It is usually combined with lamivudine, didanosine, or zalcitabine. AZT should not be combined with stavudine.

The usual dose of AZT is one 300 mg pill twice a day, taken with or without food. AZT is also combined with lamivudine in a single pill called Combivir®, which is also taken twice a day. A second combination pill, Trizivir® contains abacavir, lamivudine, and zidovudine.

Side effects, which may include fatigue, nausea, and headache, usually improve or disappear a few days to a few weeks after starting therapy. AZT is sometimes associated with a decrease in the number of red blood cells (anemia) and prolonged use can lead to myopathy.

• Didanosine (also known as ddI; Videx®, Videx EC®)
  Didanosine, which was approved by the FDA for the treatment of AIDS in 1991, usually is combined with AZT, stavudine, or lamivudine. It is sometimes combined with the anticancer drug hydroxyuria, which increases its effectiveness and side effects. This combination should be used with extreme caution.

The usual dose of didanosine is two 200 mg pills per day or one 400 mg daily, taken on an empty stomach. The pills have to be chewed or crushed and dissolved in water. A newer form of swallowable didanosine (Videx EC) is also available.

Side effects or didanosine include upset stomach and diarrhea. It can also cause painful neuropathy and pancreatitis (inflammation of the pancreas). Pancreatitis is a serious, potentially life-threatening complication that is more likely to develop in patients who have advanced HIV infection. If there are any signs of pancreatitis, this drug should not be used.

• Zalcitabine, dideoxycytidine (Hivid®)
  This medication (also known as ddC) is the third nucleoside drug approved for the treatment of AIDS and usually is combined with AZT. The usual dose is 0.375–0.75 mg three times a day, taken with or without food.

Main side effects of zalcitabine are severe peripheral neuropathy; oral and, to a lesser extent, esophageal ulcers; and, rarely, pancreatitis. Neuropathy, which can be irreversible, occurs as a side effect in as many as one-third of all patients with advanced HIV/AIDS. If numbness, burning, tingling, or pain progresses beyond moderate discomfort, the drug should be discontinued. Zalcitabine should be used with extreme caution in patients with a history of neuropathy.