April 7, 2008

Combined Resistance Analysis Better Predicts Treatment Failures

Assessing the combined results of resistance tests for Prezista (darunavir) and Intelence (etravirine) may better predict treatment outcomes than assessing resistance only to the individual drugs, according to a report at NATAP from the 6th European HIV Drug Resistance Workshop in Budapest, Hungary.

Currently, when doctors try to determine from resistance tests which combination of drugs a heavily treatment-experienced patient may respond to, they usually factor in the resistance results of each drug individually. For example, say that a person’s virus has  only one or two resistance mutations—i.e., low-level resistance—to each of three different drugs. Based on the way that resistance is currently calculated, the patient’s doctor would probably say that a regimen made up of the three drugs together would also have a low level of resistance, and be very likely to work.

Jonathan Schapiro, MD, from the Sheba Medical Center in Tel Hashomer, Israel, and his colleagues wondered, however, whether that low level of resistance to the three separate drugs could add up and cumulatively equal a higher level of total resistance to a regimen, and thus a greater chance that the regimen may fail to work. To answer this question, Schapiro’s team conducted an analysis of data from the DUET studies, which were originally designed to evaluate the efficacy and safety of Intelence, and compared people taking Prezista and Intelence, plus an optimized background regimen of other drugs, with people taking Prezista and a placebo, plus an optimized background regimen. Specifically, the team looked at how patients’ resistance to Prezista and Intelence before they began taking the drugs affected treatment outcomes.

Schapiro’s team found that adding the number of resistance mutations to each drug together yielded a better prediction for who would have a treatment failure than assessing resistance only to each drug separately. For instance, people who had two Prezista mutations and two Intelence mutations should, based on previous analysis, have a fair chance of achieving treatment success, meaning virus levels of less than 50 copies after 24 weeks of treatment. This is especially the case with Intelence, as previous analysis found that it took three Intelence resistance mutations before a person’s chance for treatment success was greatly diminished. The team, however, found that a person with just two Intelence mutations was as likely to fail as a person with three such mutations, if they also had two Prezista mutations. In other words, combining the resistance results better predicted treatment success and failure than considering the results for each drug individually.

Schapiro and his colleagues conclude that future studies should examine the impact of combined resistance scores and suggest that doctors factor this in when building regimens for treatment-experienced patients.

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