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Response from Dr. Sherer
I am a little wary of answering this question out of context, so I will answer it and provide some background as well. I will also urge you to talk to your doctor about your question and this answer, as a person in whom Prezista (darunavir) is being considered or given is likely to have a complicated treatment history and multiple resistance mutations. A single answer in isolation is not a good idea in such a case.
Prezista (darunavir) is the newest protease inhibitor. It is co-administered with ritonavir twice daily, and it has excellent activity against viruses that are resistant to most current PIs, including fosamprenavir, lopinavir, and atizanavir. In clinical trials of patients with extensive treatment histories and multiple PI mutations, it was able to achieve a viral load below detection in 30-65% of patients, depending on their level of resistance, whether or not one or more active NRTIs was in their regimen, and whether or not enfurvitide (T-20) was also added to the regimen. It is used in settings similar to tipranavir, which is also a new PI with activity against multi-PI resistant virus. As such, it has achieved much attention. It has appeared to be well tolerated, and has side effects and toxicities similar to other boosted PIs. It is NOT a "super" protease inhibitor, and resistance has been demonstrated to occur, which brings me to the answer to your question.
In one study of a panel of 9,968 isolates, >50% have >10-fold reduced susceptibility to darunavir with 3 or more of the following key mutations:
V11I, V32I, L33F, I47V, I50V, I54L, I54M, G73S, L76V, I84V and L89V
To date, the phenotype cut-offs that have been proposed are for some reduction in susceptibility at > 10 fold, and near complete loss of susceptibility at > 40-69 fold, but the clinical correlations with these cut-offs have not been established.
I doubt that these numbers are of much value to you. I encourage you to ask your question of your doctor, and to share these observations with him or her.
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