Brand Name: Retrovir

Common Name: zidovudine (ZDV), AZT

Class: nucleoside analog (also called nucleoside reverse transcriptase inhibitor, NRTI or nuke)

Standard dose: One 300 mg tablet twice-a-day (two 100 mg capsules three times a day also available), no food restrictions (may be taken with or without food). Clear, strawberry-flavored liquid available for pediatric use. Take missed dose as soon as possible, but do not double up on your next dose.

AWP: $387.38 / month

Manufacturer contact: GlaxoSmithKline, www.treathiv.com, 1 (800) 722–9294

AIDS Treatment Information Service: 1 (800) HIV–0440 (448–0440)

Potential side effects and toxicity: Most common side effects include headaches, fever, chills, muscle soreness, fatigue, nausea, and fingernail discoloration. AZT has been associated with alteration of various cells in the blood through bone marrow suppression resulting in anemia (low red blood cells) and/or neutropenia (low white blood counts), particularly in people with advanced HIV during the first three months. Potential for severe anemia requiring blood transfusion or hospitalization when used on its own or in combination with hydroxyurea. Prolonged use of high doses of AZT has been associated with symptomatic myopathy (muscle damage). Rare but potentially fatal toxicity with all NRTIs is pancreatitis (inflammation of the pancreas), hepatomegaly (enlarged liver) with steatosis and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis has been seen in patients taking NRTIs but is more common and more severe in women, people who are obese and people who have been taking nukes for a long time; and more common in people with liver disease, but can occur in people without a history of liver damage. People with lactic acidosis may experience persistent fatigue, abdominal pain or distension, nausea/vomiting, and difficulty breathing or shortness of breath; and enlarged, fatty liver (called hepatomegaly with steatosis).

Pancreatitis can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting and blood in the urine. Your physician will check for pancreatitis by checking for increased levels of amylase and lipase in the blood. Risks for pancreatitis include: higher than recommended doses of NRTIs, advanced HIV, and alcohol use. The risk for pancreatitis with AZT is low compared to didanosine.

Potential drug interactions: Biaxin, Dilantin, Mycobutin, and rifampin (under various brand names) may decrease AZT blood levels. Benemid and Depakote may increase AZT blood levels and decrease AZT clearance. Cytovene, Vitrasert and Valcyte increase AZT blood levels, and perhaps AZT-related anemia. Prescriber may need to adjust doses accordingly. AZT and Zerit should not be used together due to evidence that one limits the other’s effectiveness. Also, bone marrow supression should be monitored with use of ganciclovir, amphotericin B, pentamidine, dapsone, flucytosine, sulfadiazine, interferon-alpha, ribavirin (Rebetol), and with other antineoplastics (anti-tumor treatment) such as hydroxyurea and doxorubicin. Ribavirin and AZT may cancel each other out and may increase the risk of lactic acidosis, therefore combination use should be avoided.

Tips: Outstanding news for AZT this year: it came to the rescue of triple nuke therapy. After the bad news that the two most potent nukes, Viread and Ziagen, failed badly in the triple-nuke combination with Epivir, came the good news that the three drugs worked well in the nuke-only regimen of Trizivir/Viread. AZT (found in Trizivir) helps fight off the drug resistance problems that plague triple nukes that don’t include it. These results are still preliminary. A nuke-only regimen should only be tried by people with low viral loads (below 50,000)—see aidsinfo.nih.gov for a full discussion. The not-so-good news for people adding AZT: the fatigue and the potential anemia. You can start taking Procrit for some anemias, but that’s adding an expensive weekly injectible. Some doctors would prefer switching out the AZT for another drug. Also, some clinicians are avoiding the “T” drugs, or thymidine analogs (AZT and Zerit) because of implication in lipoatrophy. Taking with food may minimize upset stomach. Studies show that AZT crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. Proven to significantly reduce mother-to-infant transmission. Also available in Combivir (with Epivir) and in a triple combination in Trizivir (with both Epivir and Ziagen).

Doctor
Retrovir was the first anti-HIV medication approved by the FDA for the treatment of HIV/AIDS and, eighteen years later, it is still a mainstay of therapy. Retrovir’s most serious side effect is anemia, which occurs in less than five per cent of patients; it may also play a role in the lipodystrophy syndrome (see Zerit). In high doses, Retrovir penetrates the blood-brain barrier, making it useful for the treatment of some HIV-related neurological syndromes. It continues to be highly effective in preventing maternal-fetal transmission of HIV; and it is frequently part of a regimen to prevent the transmission of HIV in the workplace, especially through needle stick injuries. —Ross Slotten, MD

Activist
As the first approved HIV drug, AZT has had the most time and opportunity to reveal itself to us. It has remained a reliable and effective component of many antiretroviral regimens used by lots of people, with great success. It has proven broad application—dementia, pregnancy, and post-exposure prophylaxis, for example. A fall from favor won’t be because it lacks durability or effectiveness, but because of side effects and toxicities. Nausea, headaches, muscle pain and bone marrow suppression are all associated with it. Even though early days of testing (using doses that proved too high and very toxic—and useless without other agents to combine it with) resulted in a loss of community cred, there is no denying AZT’s utility in fighting HIV, including ARV-resistant virus. After the patent expires this year, expect to see other companies put it with their drugs in combination pills. —Heidi M. Nass