More Uses for Tenofovir?

The recently approved antiretroviral tenofovir may be particularly important, because it appears to have fewer side effects than other antiretrovirals, and also less problem with resistance. It might be ideal for prevention of maternal transmission of HIV -- and possibly could be reformulated as an effective microbicide, allowing women to protect themselves from HIV infection without relying on men. But because tenofovir was first tested in treatment of advanced HIV disease, it seems to have been largely kept on the shelf for other uses, pending more data. Trials in first-line therapy are ongoing now.

We suspect this drug deserves more attention now, even before completion of the current trials (they will not answer all the questions anyway). It could be especially important as a starting point for developing low-side-effect treatments for patients who otherwise have poor options because of severe toxicities with other drugs. In the real world, we cannot answer every question with formal trials, so we should collect experience systematically to get the best information possible. We need to investigate: if reasonably effective antiretroviral regimens with less serious side effects are possible using the drugs now approved; if major resistance to tenofovir does develop, does the virus pay a price in ways that reduces its ability to cause disease; and even whether it might make sense to use this drug alone for certain patients -- not as a good option, but possibly a better option than any other available to them.

We should also look into why this treatment was so much more effective as an antiviral in some animal trials with viruses related to HIV, than in human studies. Some of the animal tests found huge viral load reductions when the drug was used alone, compared to only about a 0.6 log reduction in patients. Could this difference have been due to the fact that the animal studies injected the active substance (PMPA), while humans use an oral prodrug (tenofovir) designed to be converted to PMPA by the body? Pharmaceutical companies have usually stayed away from any HIV drug that would have to be injected frequently. But if an injected drug had anywhere near the antiretroviral potency of PMPA in the animal trials, many people would very much want to use it. (A larger dose of the oral tenofovir is apparently not more effective, so the difference would not be just from the dose.)

ISSN # 1052-4207

Copyright 2002 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.

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