Abacavir/Lamivudine/Zidovudine (Trizivir) a Simple FactSheet from the AIDS Treatment Data Network

||||| Trizivir is a Nucleoside Reverse Transcriptase Inhibitor:

Trizivir is a combination of three Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in one pill. These three NRTIs are abacavir (Ziagen), lamivudine (3TC, Epivir) and zidovudine (AZT, Retrovir). The body breaks down these drugs into chemicals that stop HIV from infecting uninfected cells in the body, but they do not help cells that have already been infected with the virus. As people with HIV lose CD4 cells cells - one of the immune system's main defenses - they become more likely to get infections and illnesses. Ideally, Trizivir should be used as part of a carefully chosen combination of anti-HIV treatments in order to get the most benefit. Many studies have now shown that using lamivudine in combination with zidovudine and at least one other anti-HIV drug from another class (Protease Inhibitors or Non-Nucleoside Reverse Transcriptase Inhibitors) can prevent the virus from getting resistant. This has helped people live longer and develop less opportunistic infections. Since Trizivir is made of three drugs from the same class, it is recommended that Trizivir not be taken alone if your viral load is higer than 100,000. Drug resistance tests (genotypic or phenotypic) have been shown to be useful in choosing the optimal anti-HIV treatment regimen specific to an individual. See the FactSheets "Combination Therapy" & "Understanding Drug Resistance" for a detailed discussion on these subjects. New Public Health Service HIV treatment guidelines say that the best way to use Trizivir is in combination with other anti-HIV drugs. The guidelines recommend combinations of three or four anti-HIV drugs as first treatment for HIV. The recommended combinations should take one drug or combo from column A and one combo from column B (Drugs are listed in alphabetical, not priority order): Recommendation Column A Column B Strongly Recommended Sustiva Crixivan Viracept Norvir + Crixivan Kaletra Norvir + Fortovase Videx + Epivir Videx + Zerit Epivir + Zerit Videx + Retrovir Epivir + Retrovir Recommended as Alternatives Ziagen Agenerase Rescriptor Viracept + Fortovase Viramune Norvir Fortovase Retrovir + HIVID Not recommended because of insufficient data hydroxyurea in combo with ARVs Norvir + Agenerase Norvir + Viracept Viread Not Recommended and should not be offered Invirase Zerit + Retrovir HIVID + Videx HIVID + Epivir HIVID + Zerit For people that have already taken NRTI anti-HIV drugs, abacavir may not always work so well due to drug resistance. The changes in HIV that cause drug resistance are called mutations, and different mutations cause resistance to different drugs. In clinical trials, if a person's HIV already had three or more mutations that made it resistant to other NRTI drugs, abacavir did not have anti-HIV effect. Lamivudine (Epivir) is also approved for the treatment of hepatitis B (Epivir HBV). Studies have shown that Epivir can reduce the amount of hepatitis B virus to very low levels, although this effect does not always last. The treatment of Hepatitis B will likely require using combination therapy. A study has also shown that pregnant women treated with zidovudine (Retrovir) were only one-third as likely to pass HIV on to their babies as women who didn't take Retrovir. This has led to a recommendation that HIV-positive pregnant women be counseled about the potential benefits of Retrovir in preventing the transmission of HIV to their child. Retrovir is sometimes used to treat dementia. Symptoms of dementia can be forgetfulness and personality changes. Retrovir is also used to treat a blood disorder called thrombocytopenia, which means low levels of the cells that allow blood to clot.

||||| Dosage:

The recommended dosage of Trizivir is one tablet (containing 300 mg abacavir, 150 mg lamivudine and 300 mg zidovudine) twice a day. Trizivir can be taken with or without food. People who weight less than 110 lbs. should not take Trizivir.

||||| Side effects:

Since Trizivir contains three different drugs, the side effects associated with each drug also applies here. Lamivudine has few side-effects, mainly nausea, vomiting, headaches, and rare cases of hair loss. Although not as commonly as with some other anti-HIV drugs, lamivudine can cause damage to the nerves in the hands and feet. This condition is called peripheral neuropathy. The symptoms of peripheral neuropathy are burning or numbing sensations in the hands and feet which can become very painful. If lamivudine causes this problem, it may be necessary to switch to another anti-HIV drug to prevent permanent nerve damage. See the FactSheet "Peripheral Neuropathy" for other treatment options which might be helpful. Lamivudine can cause a side effect called pancreatitis, especially in children. Pancreatitis is a dangerous swelling of an organ in the body called the pancreas. People taking lamivudine should be carefully monitored for this side effect. Long-term zidovudine use is associated with myopathy(loss of muscle). Other side effects can be anemia, white blood cell depression, lip, mouth and tongue sores, bone marrow damage, headaches, skin rash, itching, weakness, nervousness, dizziness, nausea, stomach pain, confusion, loss of speech or appetite, muscle aches, fever or sweating, sore throat or abnormal bruising or bleeding. In African-Americans, zidovudine can cause changes in nail color. Studies indicate that possible blood cell damage may be prevented or treated by taking vitamin E, epoeitin alpha (EPO) or G-CSF with this drug. Nutritionists recommend taking manganese and B vitamins with this drug.

||||| Side effect warning!

Hypersensitivity (allergic) reactions to abacavir have been reported in approximately 3-5% of people in the clinical trials. Symptoms began an average of 11 days after starting the drug. Symptoms were a general sick feeling, low grade fever and nausea, with or without vomiting. There can also be symptoms that affect breathing, such as shortness of breath, cough and sore throat. In some people, a rash appeared 1-3 days after onset of these symptoms. All symptoms resolved within 1-2 days after stopping treatment. If treatment was started again at reduced doses, potentially fatal symptoms developed within hours. Several study participants who tried to restart abacavir after having a hypersensitivity reaction had to be hospitalized, and two people died. Study participants are now being told to report any flu-like symptoms with or without rash beginning several days to 4 weeks after starting treatment, and to stop treatment immediately if symptoms occur. Treatment with abacavir should not be restarted. Some people have experienced potentially fatal symptoms after restarting abacavir even though they did not stop the drug due to a hypersensitivity reaction. In these reports, people interrupted treatment with abacavir for other reasons and were not having problems with abacavir when they stopped. When they restarted the drug, they developed the same severe life-threatening symptoms as those seen in people who stopped due to an allergic reaction. Several people are thought to have died as a result. Restarting abacavir after an interruption should be done with extreme caution and only when emergency medical care is easily accessible. The other side effects that have been seen so far with abacavir include increased fatigue, changes in liver function tests, headache, abdominal pain, constipation, diarrhea, nausea, vomiting, sleeplessness, skin rash, and dizziness.

||||| Allergic Reaction Registry:

A special toll-free number has been set up for reporting cases of hyper-sensitivity (allergy) to abacavir. The number to call is (800) 270-0425. A new warning letter about fatal hypersensitivity re-actions to abacavir can be dowloaded from the Internet at: http://www.fda.gov/medwatch/safety/2000/safety00.htm#ziagen

||||| Warnings:

A set of rare but serious side effects of nucleoside analog anti-HIV drugs is called lactic acidosis and severe hepatomegaly with steatosis (an enlarged fatty liver). Women, especially those who are oveweight, are particularly at risk. This set of side effects is probably the result of mitochondrial toxicity. Mitochondria are cell's power organs that supply the energy needed for normal cell growth. Anti-HIV nucleoside analogs impair the function of mitochondria. This can lead to increased acid levels in the blood, and an enlarged fatty liver. The symptoms are severe nausea, shortness of breath and vomiting that does not get better. If you are taking anti-HIV drugs and experience these symptoms, tell your provider immediately. If you're going to use lamivudine, it's important to check for infection with hepatitis B. If you have active hepatitis B when you start lamivudine, you may feel sick for a month or two because liver cells infected with hepatitis B die off. Liver enzymes may also increase temporarily. These symptoms are a lot like some drug side effects, and knowing your hepatitis status can help tell the difference. There have also been several reports of hepatitis B flare-ups when lamivudine treatment is stopped. Symptoms of hepatitis B flare-ups are high liver enzymes, yellow skin (jaundice), nausea, vomiting, fatigue, abdominal and joint pain. Call The Network at 212-260-8868 or 800-734-7104 for more information on Hepatitis and HIV co-infection. GlaxoSmithKline, the maker of Trizivir, has a patient assistance program for people having problems getting the drug. The number to call is (800) 722-9294.

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