• Safety Profile of Tenofovir DF (TDF) in Antiretroviral Treatment-Experienced Patients From Randomized, Double-Blind, Placebo-Controlled Clinical Trials (TuPeB4460)
  Authored by A. Cheng, S. Barriere, D.F. Coakley, S.S. Chen, M. Wulfsohn, J.J. Toole
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Tenofovir (Viread) is the latest antiretroviral to be approved in the U.S. and Europe. It is the first of a new class, the nucleotide reverse transcriptase inhibitors. Because it is a member of a new class, and because earlier drugs in this class -- cidofovir and adefovir -- had kidney toxicity, there has been a lot of interest in the safety profile of tenofovir. However, to date, tenofovir has been one of the best tolerated and safest HIV drugs that we have looked at.

Andrew Cheng from Gilead presented a poster pooling all of the data on the approved dose of tenofovir, 300 mg, from the studies in treatment experienced patients, studies 902 and 907. These have been described at previous conferences. A total of 687 patients were treated with tenofovir compared to 210 on placebo. It is important to remember that all of these patients were on a variety of other antiretrovirals drugs, and many had advanced HIV disease. The mean followup was 95 weeks; 443 had at least 24 weeks.

The bottom line is that no symptom was more common in the tenofovir group than among those who added placebo. As many patients stopped placebo due to adverse events (9 percent) as stopped tenofovir (7 percent). Laboratory abnormalities were examined carefully since there has been some inconsistent evidence of bone metabolism problems in some species of young animals, and the class of drugs has kidney toxicity. There was no statistically significant differences in changes in kidney function or in serum phosphorus, a measure of bone metabolism.

However, it is important to remember that we only really understand drug toxicity after years of use in tens of thousands of patients. Thus, even though early data are reassuring, we need to keep watching to see if the other shoe may drop. This study is still relatively small by those standards, and the treatment duration is beginning to get up to a range that matters, but it is still relatively early. A large and important study of tenofovir (study 903) as first-line therapy will be presented later this week. Toxicity was also very reassuring in that study. More importantly, detailed studies of bone and fat are being done in that study. When those are complete, study 903 will prove to be of huge importance.

Two take home messages seem important to me. First, we continue to gradually move to HAART regimens that are safer, better tolerated and use fewer pills. Secondly, all drugs, vitamins and herbs can have side effects. We shouldn't get caught up in hailing anything as totally safe, nor should we overreact when we begin to learn that some side effects will effect some people. It is always a question of balance -- do the benefits outweigh the risks or inconveniences. If we remember the millions who have died and suffered from the disease, we will keep toxicity in context when we have effective treatment. Likewise, we need to keep watching for side effects, not only after months, but after years of treatment.