Co-treatment with Didanosine and Tenofovir Raises Risk of Pancreatitis

By Anthony J. Brown, MD

In a new study, HIV-infected patients treated with didanosine (Videx; ddI) and tenofovir (Viread) were about 11-times more likely to develop pancreatitis than their peers who were treated with either agent alone. The rate of this adverse effect was highest for women weighing 60 kg or less, according to the report in The Lancet for July 3rd.

The elevated risk of pancreatitis seen when "didanosine and tenofovir are given together is a new finding," Dr. Marta Boffito, co-author of a related editorial, told Reuters Health. However, she noted that the absolute risk of pancreatitis with concomitant use remains low and in some patients this combination may be warranted because of resistance issues.

As to how the two drugs interact to promote pancreatitis, Dr. Boffito, from Chelsea and Westminster Hospital in London, said the mechanisms are unclear. However, given that didanosine alone has been linked with pancreatitis and that tenofovir has been shown to raise didanosine levels, it's possible that tenofovir is simply increasing didanosine levels to a point where pancreatitis is more likely, she said.

The findings are based on a study of 575 patients whose antiretroviral regimens included didanosine plus tenofovir or either agent alone. The subjects were followed for over 2 years.

During the study period, the rate of pancreatitis in the didanosine/tenofovir group was 2.7%, significantly higher than the rates seen in the didanosine- (0.5%) and tenofovir-only (0%) groups, lead author Dr. Esteban Martinez and colleagues, from the University of Barcelona in Spain, note. In the didanosine/tenofovir group, the highest incidence of pancreatitis (13.3%) occurred among women weighing 60 kg or less.

"Sometimes you really need to use didanosine and tenofovir together," so I wouldn't recommend abandoning this combination, Dr. Boffito said. "But, I do think the findings highlight the importance of close monitoring for patients" treated with both of these agents.

07/02/04

Lancet 2004;364:8-10,65-67.