Potential side effects and toxicity: Overall, fairly well tolerated, however, individuals may experience the following: nausea, headache, diarrhea, vomiting, asthenia, flatulence, abdominal distension/pain and anorexia. Less common side effects of tenofovir occurring with undetermined incidence include kidney toxicities and low blood phosphorate. See AZT page for rare but potentially fatal toxicity with all NRTIs as a drug class.
The effect of tenofovir on children and individuals with severe hepatic (liver) impairment was not studied during drug development. However, since tenofovir 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. See tips. Viread decreases the concentration levels of Reyataz. In addition, Reyataz (and Kaletra) increases Viread concentrations. Higher Viread concentrations could increase the risk of Viread-associated adverse events, including renal 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.
Tips: To its credit, Viread is successful in showing viral load decrease in people with nuke resistance. In three years of follow up studies, it continued to demonstrate good results in people whose current triple-class therapy is failing. 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 has been in those with pre-existing kidney disease or receiving nephrotoxic agents. However, the characteristics of renal 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 about 20 reports on 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. See Trizivir and AZT pages for successful results combining Viread with Trizivir. The drug resistance pattern of AZT in Trizivir was found to save the day for the nuke-only combination containing the potent Ziagen and Viread.
Bad news in combination with Videx—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—was met with nonchalance by many doctors, whose patients do well when taking the two drugs together. BMS sent a warning letter to doctors in 2004 reporting early virologic failure (detectable viral load) in a tiny number of people on HIV meds for the first time who were taking the combo with either Sustiva or Viramune. However, the letter points out that these individuals started out with a high viral load (not defined, but usually refers to more than 100,000) and that Viread and Videx-EC does well with protease inhibitors. But a larger study also found early failure (at 12 weeks) with Sustiva/Videx/Viread (12%, five out of 41 individuals) vs. Sustiva/Videx/Epivir (no failures at 12 weeks).
Like Epivir, Viread has activity against hepatitis B. Hepatitis B may flare up when Viread is discontinued. While data is limited, it appears that Viread can have prolonged activity against hepatitis B even when resistant to Epivir. Viread selects for the K65R mutation (as do Ziagen and Videx), it was seen in 3% of the Viread treatment-naïve patients at two years. But Viread may continue to be effective despite this resistance. AZT and Zerit maintain full activity and varying rates of continued efficacy are seen with Ziagen and Videx. In clinical trials reduced response to Viread was associated with multiple TAMs (thymidine analog mutations), specifically the M41L or L210W. Further research needs to be done in this area. Available in a combination pill with Emtriva.
Doctor
TDF is a nucleotide analog, but it has the same mechanism of action against the virus as the other nucleosides. It is potent, dosed once daily, and is very well tolerated by most patients. The most commonly reported side effect is upset stomach. There is increasing concern among providers of the potential kidney toxicity of this agent, although further studies are underway to clarify this issue. It should be used with caution in patients with pre-existing kidney problems, diabetes, or high blood pressure. There is also concern for long-term demineralization (weakening) of bones, but this has not been proven in studies. There is a significant drug-drug interaction with Videx (requiring dose reduction of Videx). Viread also reduces plasma levels of Reyataz. When Viread and Reyataz are given together, Reyataz must be boosted with ritonavir to overcome this effect. Viread also has potent activity against hepatitis B.—Chad J. Zawitz, MD
Activist
This is one of the bestselling HIV drugs nowadays, and for many reasons. It is taken once a day, is durable, can treat hepatitis B, and does not cause lipoatrophy, neuropathy, and lipid problems. Many doctors are switching their patients from drugs that may cause lipoatrophy (d4T and AZT) to this drug since some studies show that lipoatrophy may improve slowly after that switch. But Viread is starting to worry some people when it comes to kidney dysfunction, especially in the older and more advanced patient population. Be very careful if you are still taking it with ddI, even at 250 mg of ddI (see ddI). Also, have your doctor calculate your creatinine clearance every three months just to make sure you are not developing early kidney disease. You can visit this web site for an easy calculation of your creatinine clearance: http://www.intmed.mcw.edu/clincalc/creatinine.html.—Nelson Vergel
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