One tablet once daily

Brand name: Viread

Common name: tenofovir disoproxil fumarate (TDF)

Class: nucleotide analog (also called nucleotide reverse transcriptase inhibitor—part of the nucleosides—NRTI, or nuke)

Standard dose: One 300 mg tablet once-a-day, with no food restrictions (with or without food). Take missed dose as soon as possible, but do not double up on your next dose.

AWP: $485.56 / month

Manufacturer contact: Gilead Sciences, Inc., www.viread.com, 1 (800) GILEAD5 (445–3235)

AIDS Treatment Information Service: 1 (800) HIV–0440 (448–0440)

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. See AZT page for rare but potentially fatal toxicity with all NRTIs as a drug class (they have not been seen with Viread).
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 (ddI) 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. The reasons for these interactions are not fully understood. Higher Viread concentrations could increase the risk of Viread-associated adverse events, including renal disorders. The FDA suggests that 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 and Viread 300 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. More research is needed. 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.

Recent 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 late last year 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 does Ziagen and Videx), it was seen in 3% of the Viread treatment-naive patients at two years. But Viread continues 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.

Doctor
Viread is a nucleotide analog, though it is classed with the nucleoside reverse transcriptase inhibitors. Like Epivir and Emtriva, it is well tolerated, though rarely it can impair kidney function, which returns to normal when the medication is stopped. Viread can interact with other anti-HIV medications, especially Videx and Reyataz. Other interactions may emerge in future studies.
Activist
After tenofovir was approved, the FDA got after Gilead a few times for overstating the drug’s safety profile and potency in its promotions. (My rule: if there ever is a “miracle drug,” as Gilead described Viread, we won’t just hear about it in the company’s ads.) Turns out, tenofovir is a fussy drug. It’s potent and durable, but it doesn’t play well with other once daily options: ddI, abacavir, atazanavir.... Tenofovir is cleared by the kidney (and will compete with other drugs cleared by the kidney, including some commonly used antivirals), so kidney function should be monitored closely. Despite an unfolding story of drug interaction (next up: Kaletra), tenofovir keeps showing its potential: possible maintenance therapy with efavirenz? Added to Trizivir as a second-line therapy? It’s a drug on the move. Note: if you have HBV, the warning about stopping 3TC and FTC and risk of hepatic flare holds for tenofovir, too.

Nukes | Retrovir / AZT / zidovudine | Videx, Videx EC / ddI / didanosine |
| Hivid / ddC / zalcitabine | Zerit / d4T / stavudine | Epivir / 3TC / lamivudine |
| Ziagen / abacavir sulfate | Combivir (Retrovir, Epivir) |
| Trizivir (Retrovir, Epivir, Ziagen) | Emtriva / emtricitabine / FTC |
| Viread / tenofovir disoproxil fumarate | Epzicom (Epivir, Ziagen) |
| Truvada (Viread, Emtriva) |

Non-Nukes | Rescriptor / delavirdine | Viramune / nevirapine |
| Sustiva / efavirenz |

HIV Protease Inhibitors | Invirase / saquinavir hard-gel | Crixivan / indinavir | Norvir / ritonavir | Viracept / nelfinavir | Fortovase / saquinavir soft-gel |
| Agenerase / amprenavir | Kaletra (lopinavir/ritonavir) |
| Reyataz / atazanavir | Lexiva / fos-amprenavir | tipranavir |

Fusion Inhibitor | Fuzeon / T-20 / enfuvirtide |

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