tenofovir (Viread) a Simple FactSheet from the AIDS Treatment Data Network

||||| Viread is a Nucleotide Reverse Transcriptase Inhibitor:

Tenofovir (Trade name Viread) is an anti-HIV drug approved by the FDA (In October of 2001) to be used in combination with other HIV fighting medications. Viread belongs to a new class of drugs called Nucleotide Reverse Transcriptase Inhibitors (NtRTI). These are related to Nucleoside Reverse Transcriptase Inhibitors (NRTI) like zidovudine (AZT, Retrovir). The body converts Viread into a chemical that prevent HIV from reproducing in uninfected cells, but it does not help cells that have already been infected with the virus. As people with HIV lose CD4 cells - one of the immune system's main defenses - they become more likely to get infections and illnesses. Currently available anti-HIV drugs like AZT need three separate chemical steps before they are active. Viread needs only two chemical reactions (phosphorylation) to occur before it can start working. Partly due to this unique chemical feature, Viread also carries a "negative charge", allowing it to stay in the cells where it is active for a longer period. As a result, Viread only needs to be taken once a day.

||||| Trial Results:

Viread was approved based on two clinical trials involving 736 people with an average CD4 cell count of about 400. These volunteers had taken anti-HIV medications for an average of five years. They were having difficulty suppressing HIV with their current combination therapies. Based on genotypic resistance test results, about 94% of the volunteers had at least one NRTI (like AZT) resistant strain of HIV. Volunteers in Trial 902 had an average of 5012 viral load (range 52-575,000) at the start of the trial. Viread was added to existing combination therapies using variously: didanosine (DDI, Videx), lamivudine (3TC, Epivir), indinavir (Crixivan), efavirenz (Sustiva), and lopinavir/ ritonavir (Kaleatra). After 24 weeks, 19% of the volunteers were able to get their viral load below 400. 11% were able to lower it to less than 50. In Trial 907, participants started off with a lower average viral load of 2340 (range 50-75,900). After 24 weeks, 40% of the volunteers were able to get their viral load below 400. 19% were able to lower it to less than 50. At the end of both trials, Volunteers had an average increase of 11 CD4 cells. Even though these results have shown Viread's ability to lower and suppress HIV levels in the blood, it has not been shown to significantly increase CD4 cell levels. This might be due to the fact that these trials were conducted with people who had been on combination therapy for a while and had fewer CD4 cells to work with. Since the drug's approval, other trials involving people who have not previously taken anti-HIV medications have demonstrated that Viread is also effective as a first line treatment.

||||| Dosage:

Viread is easily absorbed and stays active in the body for many hours. It only needs to be taken once a day (one 300 mg blue pill), making it easier to stick with a treatment regimen. Viread should be taken with a high fat meal, doing so provides higher blood levels of the drug. A children's formulation is under development. It is expected to be available in early 2002. New Public Health Service HIV treatment guidelines say that the best way to use Viread 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

||||| Resistance Profile:

When used in combination with other anti-HIV drugs, Viread has been found to work in people who have developed resistance to NRTI drugs. It may work better in people who have a strain of HIV that is resistant to lamivudine (Epivir, 3TC). Before adding Viread to your treatment regimen, you might want to have a discussion with your medical provider about getting a genotypic drug resistance test. This test can find out if you have a strain of AZT resistant HIV with the K65R mutation. It is the only known mutation that may cause Viread to be less effective, though this has not been observed in clinical trials.

||||| Drug Interactions:

The body clears out Viread through the kidneys. It does not compete with most other anti-HIV drugs that are metabolized by the liver, reducing the workload for these important organs. With the exception of didanosine (ddI, Videx), Viread does not affect the level of other drugs in the body. Viread increases Videx levels, but adverse effects have not been noted so far. People taking both Videx and Viread should be monitored closely for adverse effects associated with Videx. It is also recommended that Viread be taken two hours before or one hour after taking Videx. This is because, unlike Viread, Videx needs to be taken with an empty stomach. Studies of Viread with Videx EC, a long acting, non-buffered version of ddI, have not been conducted.

||||| Side Effects:

The potential side effects of Viread are nausea, diarrhea, vomiting and flatulence. In animal studies using much higher dosages, a loss of bone density developed. When the dosage was lowered, these symptoms disappeared. Trials are still under way to find out long term side effects. Two years of human research indicate that problems like kidney toxicity are rarely observed, although they were seen with a related drug, adefovir. Viread has not been studied in people with known kidney or liver problems such as hepatitis.

||||| Warning:

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. Viread has been shown to work well in both women and men. There is not enough information so far on whether it works the same in all racial and ethnic groups. It is not recommended for women who are pregnant or breast-feeding, because trials have not yet been done on this group of people. Due to its potential long-term side effects on the kidney and the liver, it is not recommended for people with kidney or liver problems at present time. Your doctor should also keep an eye on your creatine level (kidney damage indicator) and watch for possible long-term problems. Gilead Sciences, the maker of tenofovir (Viread), has a Reimbursement and Assistance Program for people having problems getting the drug. The number to call is (800) 226-2056. To find out if a drug is covered by your state's AIDS Drug Assistance Program or Medicaid, call The Access Project at 212-260-8868 or 800-734-7104.

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