Since the introduction of the antiviral tenofovir (TDF, Viread), there has been interest in using this drug in a variety of settings. One attractive feature of tenofovir is that it has a different, often reduced, adverse event profile compared to other drugs in the same class. Because of this potentially important clinical advantage, Miralles Alvarez and colleagues conducted a large clinical study in which tenofovir was used instead of another nucleoside antiviral.
The researchers in Spain reported on a cohort of 902 patients in whom tenofovir was started as a replacement for another nucleoside antiviral. This group was identified as needing a replacement because of some ongoing toxic effects of one of their current nucleoside antiviral agents. The majority of patients (68%) stopped stavudine (d4T, Zerit), while 12% stopped zidovudine (AZT, Retrovir), 13% stopped didanosine (ddI, Videx), and 7% stopped other nucleoside antivirals. Most of the resulting tenofovir-containing regimens included either efavirenz (EFV, Sustiva, Stocrin) or nevirapine (NVP, Viramune) in combination with lamivudine (3TC, Epivir).
Tenofovir replacement resulted in significant improvements after 24 weeks. Overall, lipoatrophy improved in 13% of patients, and lipodystrophy improved in 12%. The authors noted, however, that about 84% showed no change in these clinical conditions after 24 weeks. In addition, neuropathy was resolved in 29% of patients, and improved in an additional 33%, although 40% reported no change.
Finally, there were significant changes in anemia and liver function test abnormalities, though no details were given about the extent of these changes. Very few of those who started tenofovir reported any deterioration in any of these side effects, consistent with other studies of this drug, which have been reassuring with regard to these particular adverse events. The investigators did not report on any tenofovir-specific adverse events, but other studies have demonstrated the overall favorable tolerability profile of this antiviral.
These results support the common clinical practice of using the newer antivirals as replacements for previously used drugs that are limited by their side effects. Because tenofovir has a generally lower side-effect profile, it is not surprising to see overall benefits in patients who substituted tenofovir for another drug. However, if this strategy is to be used, clinicians and patients need to be reasonably confident that tenofovir will be equally active as the drug to be replaced, since this study did not report on the frequency of viral load rebounds after the substitution was made. Nevertheless, the data suggest that many patients confronting ongoing toxicity on their current regimens may find that tenofovir offers potentially important advantages for improving long-term treatment success.