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Lessons From Two

March 26, 2004

Last year two three-drug regimens that had once seemed reasonable (tenofovir + 3TC + abacavir; also tenofovir + 3TC +ddI) were found to work very badly; these combinations must never be used alone as antiretroviral treatment, because they fail in most patients and cause serious drug resistance. There were different theories of why these three-drug regimens failed, but now it is widely believed that the main problem is that they did not provide a high enough genetic barrier to the development of two viral mutations, K65R and M184V, which led to resistance to the drugs.

(The picture is different for the four-drug combination AZT + 3TC + abacavir + tenofovir, which is showing good results even though it contains one of the problematic combinations within it. The AZT helps prevent the K65R and M184V resistance pattern from developing.)

On March 31 Clinical Care Options published a half-hour training module for physicians (but available to anyone) explaining this situation, and what has been learned from it. This module, titled "Lessons Learned: The Perils of Extrapolation -- Combination NRTI Use" will be available for one year at:

Under "Treatment Update," click "Lessons Learned." Note: free one-time registration is required to use this site.

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