POSITIVELY AWARE MARCH/APRIL 2011
brand name: Trizivir
common name: abacavir sulfate, zidovudine, and lamivudine
class: Nucleoside analog reverse transcriptase inhibitor
(nucleoside analog, NRTI, or nuke)—fixed dose combination
manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872
Standard dose: One tablet (300 mg Ziagen/abacavir/ABC, 150 mg Epivir/lamivudine/3TC, and 300 mg Retrovir/zidovudine/AZT), twice a day, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.
AWP: $1,608.36 / month
Potential side effects and toxicity
The most common side effects of Trizivir are the same as those of the drugs it contains—see Epivir, Retrovir, and Ziagen. Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on abacavir; see Ziagen. A simple and inexpensive blood test for HLA-B*5701 (a genetic marker) can identify people at high risk for this reaction and virtually eliminate HSR. The HLA-B*5701 test should never be used to diagnose HSR. Do not use a skin patch test to confirm HSR. Regardless of the results, it is important to monitor the potential for this reaction. If HSR is suspected or cannot be ruled out, products containing abacavir should be discontinued. If treatment is stopped because of this serious reaction, you can never take products containing abacavir, such as Epzicom, Trizivir, or Ziagen, again (called “re-challenging”). Rechallenging can cause a rare life-threatening reaction. (This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days). Symptoms worsen, very slowly, with every dose. Symptoms usually, but not always, include some combination of sudden fever; muscle ache; severe nausea, vomiting, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, and sore throat); and possibly rash. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should keep the warning card with you. Hypersensitivity might be confused with flu during flu season, but remember that HSR worsens with every dose. Check with your doctor if you have any side effects after taking this medicine—don’t just stop! See Ziagen and More Information below. Some observational studies seemed to indicate that abacavir may increase the risk of cardiovascular events, including heart attacks, in people with greater risk factors (such as smoking, diabetes, high blood pressure, and drug use); the risk is reversible upon discontinuation. Studies examining this possible association are inconclusive. One explanation for the unexpected link was that people with kidney problems were put on Ziagen to avoid medications containing Viread, which have potential for kidney toxicity. These individuals already have a strong risk for cardiovascular disease. Other side effects associated with Trizivir may include headache, nausea, upset stomach, and fatigue. May be taken with food to decrease potential nausea associated with AZT. The AZT in Trizivir has been associated with alteration of various cells in the blood through bone marrow suppression, resulting in anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Zidovudine is also associated with lipoatrophy (fat loss in the arms, legs, face, and/or buttocks—sometimes called “AZT butt”). The lipoatrophy could be irreversible or fat could take a long time to rebuild.
Potential drug interactions
See the drugs contained in Trizivir—AZT, Epivir, and Ziage, for details. Do not take Trizivir with Atripla, Emtriva, Epivir, Epivir-HBV, Epzicom, Retrovir (AZT), rilpivirine/Truvada, Truvada, or Ziagen; all or part of these medications are already in Trizivir or have equivalent medications. If you’re taking any of the following medications, consult your doctor or pharmacist before starting Trizivir: Zerit (stavudine), ribavirin, interferon, rifampin, probenecid, methadone, Cytovene (ganciclovir), Valcyte (valganciclovir), Biaxin (clarithromycin), Daraprim (pyrimethamine), flucytosine, Fungizone (amphotericin B), doxorubicin, and hydroxyurea.
More information
See the drugs contained in Trizivir—Epivir, Retrovir (zidovudine, AZT), and Ziagen. Trizivir is the only triple combination NRTI that has been studied in a randomized, controlled study, which has shown it to be inferior to the standard treatment of two NRTIs plus Sustiva. U.S. treatment guidelines recommend that Trizivir should only be used if other options are not available due to toxicities or drug interactions associated with other HIV regimens. See package insert for more complete information on potential side effects and interactions.
Doctor’s comments
In the early years of the HAART era, when people were suffering on effective but complex and toxic regimens like Combivir plus Crixivan, Trizivir appeared like a breath of fresh air. Just one pill twice a day, with no need to watch the clock or time your meals, and no kidney stones, diabetes, dry skin, cracked lips, or ingrown toenails to worry about. Sure, some people developed abacavir hypersensitivity reactions (see Ziagen), and many had the usual AZT side effects (see Retrovir). But compared to what we had before, it seemed almost too good to be true. Well, it was. This “triple-nuke” regimen was shown to be less effective than a regimen containing Sustiva, both at high and low viral loads, and its use declined rapidly after that. Today, if you had some reason to be taking AZT, 3TC, and abacavir, it would make sense to take them in the form of Trizivir. But taking Trizivir alone is no longer recommended. —Joel Gallant, MD, MPH
Activist’s comments
A mash-up of all of GSK’s (now ViiV’s) nukes: AZT, 3TC and Ziagen, Trizivir’s promise as a convenient single pill regimen was sadly unfulfilled. Subsequent studies showed Trizivir to be inferior to the two class/three drug combos that are now standard of care. It also combined the anemia, fatigue, and possible fat loss from AZT, with the danger of a hyper-sensitivity reaction and possible cardiovascular risk from Ziagen. But it did pave the way for combos like Atripla that have revolutionized HIV treatment. —Jeff Taylor
