慢性丙肝的治疗进展ppt课件.pptVIP

NUC, nucleotide analogue. * NS5A, nonstructural protein 5A; Nuc, nucleotide. So, if we think about these different classes of drugs, it’s relevant to consider how they match up to each other on different categories. And so, what you can see is the different categories of drugs across the top and some of these characteristics in the different rows. If we start with the first-generation protease inhibitors, telaprevir and boceprevir, you can see that these do not do all that well on any of the categories with a poor resistance profile—they only cover genotype 1 effectively. Although they’re reasonably potent antivirals, they are associated with a number of adverse events. So, you can see a lot of red lights in that category. ? ? The second-generation protease inhibitors are really improved in terms of their adverse event profile and they are more potent, but they still have only a moderate expansion of the genotypic coverage and still have a limited barrier to antiviral resistance. And similarly, the NS5A inhibitors are extremely potent and very well tolerated but have a low barrier to resistance and, again, a suboptimal complete coverage of the different genotypes. ? Now, you see a fair number of green lights in the nucleoside polymerase inhibitor category, and this is because this group of direct-acting antivirals has a very high genetic barrier to resistance, which I’ll discuss more later, and it seems to cover all of the 6 major HCV genotypes. They’re extremely potent and in fact, at least to date, seem to be very well tolerated. The reason this still gets an average adverse event profile and not a green light is because, at least in this class of drugs, as they’ve been developed we have seen that although they seem to be well tolerated, there have been some important and quite significant toxicities of drugs identified in small numbers of patients taking drugs from this class in clinical trials. And in some cases, this has led to the discontinuation of potent