tenofovir disoproxil fumarate (TDF)
Class: nucleotide analog (also called nucleotide reverse transcriptase inhibitor—part of the nucleosides—NtRTI, or nuke)
Standard dose: One 300 mg tablet once a day, with no food restrictions (with or without food). Dosing frequency needs to be adjusted for people with decreased kidney function. Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $578.87 / month
Manufacturer contact: Gilead Sciences, Inc.,
www.viread.com, 1 (800) GILEAD5 (445–3235)
1 (800) HIV–0440 (448–0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: Overall, fairly well tolerated, however, individuals may experience diarrhea, nausea, vomiting, and gas as the most common side effects of Viread. Viread has some efficacy against hepatitis B, and people may see a flare-up of their hepatitis B if they stop Viread. In some studies, laboratory tests showed changes in the bones. It is not known whether long-term use of Viread will cause damage to the bones. Less common side effects of Viread occurring with undetermined incidence include kidney toxicities and low blood phosphate. See zidovudine (AZT) page for rare but potentially fatal toxicity with all NRTIs as a drug class.
The effect of Viread on children and individuals with severe liver impairment was not studied during drug development. However, since Viread is not metabolized by the liver (and appears to have less toxicity in the liver than the majority of the NRTIs), it is believed the impact on individuals with liver disease should be minimal.
Potential drug interactions: The levels of Videx EC and Videx are increased by 44–60% when given at the same time as Viread. Therefore, a dose reduction to 250 mg for Videx is recommended for people who weigh more than 60 kg (132 pounds) and to 200 mg for those who weigh less than this. See tips. Viread decreases the concentration levels of Reyataz. In addition, both Reyataz and Kaletra increase Viread concentrations. Higher Viread concentrations could increase the risk of Viread-associated adverse events, including kidney disorders. Patients receiving Reyataz and Viread should be monitored for Viread-associated adverse events. When taken with Viread, it is recommended that Reyataz 300 mg is given with Norvir 100 mg (all as a single daily dose with food). Reyataz without Norvir should not be taken with Viread. Do not take with Truvada or Atripla, since Viread is in these medications.
Tips: Viread along with Emtriva (also available as Truvada and in Atripla) are considered a preferred NRTI combination by U.S. HIV treatment guidelines. The body clears 70–80% of Viread through the kidney and dosing adjustment is recommended for those with impaired kidney function. Serious kidney problems have been rare and the majority have been in those with pre-existing kidney disease or receiving kidney toxic drugs. However, the characteristics of kidney toxicity are still being defined. The manufacturer recommends that individuals with impaired kidney function be monitored closely, especially in people with advanced HIV disease, even in people who did not start out with kidney disease. There have been reports of individuals who experienced severe kidney disorder, including some taking Kaletra with Viread. Since Kaletra increases blood levels of Viread, it may increase the likelihood of Viread side effects.
Bad news in combination with Videx in a small study of treatment-naïve individuals—barely raising T-cells in people who are undetectable, failure to reach undetectable in people who started with less than 200 T-cells and more than 100,000 viral load.
Like Epivir and Emtriva, Viread has activity against hepatitis B, which may flare up when Viread is discontinued. These patients should be closely followed by their physician. While data is limited, Viread may have prolonged activity against hepatitis B even when resistant to Epivir. Viread selects for the K65R mutation (as do Ziagen and Videx). This mutation can reduce susceptibility to other nukes. The activity of Viread can be reduced in patients who have acquired resistance to other nukes. The complex interaction of nuke resistance and Viread susceptibility is an area of research. Further research needs to be done in this area. Available in a combination pill with Emtriva called Truvada and it is also combined with Sustiva and Emtriva in a pill called Atripla. Please see package insert for more complete potential side effects and interactions.
Tenofovir, usually combined with FTC, has become a favorite nuke for first-line therapy. Studies have shown that it’s safer than d4T and is less toxic, more effective, and less prone to resistance than AZT. It’s easy to take and well tolerated: other than gas, it has few side effects. The only down-side is the possibility of kidney damage, but that’s very unlikely in people who have healthy kidneys to start with. Kidney function should be monitored if you’re on Viread, Truvada, or Atripla (with the same tests that would be done anyway). Be careful about taking other drugs that can damage the kidneys. For example, avoid taking a lot of ibuprofen or other over-the-counter non-steroidal anti-inflammatory drugs.—Joel Gallant, M.D.
Viread was the first highly successful product of Gilead Sciences. It is generally believed to be the most potent of the nucleoside/nucleotide class and also the least toxic. The drug is not recommended though for people with a history of kidney disease and it doesn’t combine well with a few other antivirals. But overall, it has been a highly successful drug both for patients and for the company. It is under study today for possible use as a preventive therapy, in which the drug is given to people who are at risk of HIV but are not yet infected. Some people fear that the drug still might cause kidney problems in people without a prior history of this, but clinical trial data does not bear this out. A number of physicians report individual cases of kidney disease but not enough yet to suggest a major problem. The biggest problem Gilead has faced with Viread has been in learning how to get it approved for use quickly in developing nations, where there is great interest in the drug. The company has stumbled and made some poor choices in this effort and this has caused a bit of conflict with activists working on behalf of international access to treatments.—Martin Delaney