November 21, 2002
ddI is a highly effective antiviral also available for once-daily dosing. However, due to the food restrictions with ddI (it has to be taken without food, in a fasted state), many individuals have chosen alternative therapies that they find easier to comply with. ddI has to be administered in the fasting state because the area under the curve (i.e., exposure) is reduced by approximately 25 percent when taken with food.
However, previous evidence has suggested that when tenofovir is dosed with ddI, a drug interaction occurs which leads to higher levels of ddI. Because of these results, it has been suggested that the dose of ddI should be reduced when used with tenofovir, and that it may be possible to remove the food restrictions with ddI. This would clearly lead to the possibility of an easy-to-take nucleoside/nucleotide backbone of tenofovir/ddI, which could be taken once daily, and ease the compliance problems associated with ddI therapy while providing a potentially highly effective backbone.
Certainly at our unit at Chelsea and Westminster Hospital in London this has been common practice. We have not observed an increase in adverse events, and many patients have commented that minor ddI-related adverse events such as dry mouth, have either disappeared or been reduced by this dosing strategy. Some authors have suggested that even with the reduction to 250 mg there may still be a cause for greater ddI exposure and therefore more severe toxicities such as pancreatitis. This has not been observed at our unit.
The other advantage of this dosing strategy is that tenofovir, ddI and other once-daily drugs may be given as true once-daily therapy. Many patients have also commented on the relative ease of administration of such a regimen compared with when ddI was dosed with food restriction. Further studies are ongoing looking at different doses of ddI with tenofovir with food, and physicians and patients need to make their own decisions regarding the relative risk of dosing these drugs together as against the probable efficacy of such a regimen and ease of administration.
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