Is nevirapine-based therapy discontinuation in hepatitis C co-infected patients a more important mortality determinant than hypersensitivity: authors' reply

We thank Raffi et al. [1] for their comments regarding our study [2] on the nevirapine-related hypersensitivity reaction (HSR) in hepatitis C virus (HCV) co-infected individuals as an effect modifier for increased mortality. Raffi et al.[1] point out several limitations of our study, related to the definition of nevirapine-HSR, which were addressed in detail within the discussion section of our article. For example, we acknowledged that our rate of HSR was higher than that reported in other studies [2], as well as the difficulty of comparing our results with others due to differences in definitions and the diversity of populations studied. The possibility for nondifferential misclassification bias, which may have conservatively biased our results, was further cited as a limitation in the discussion section [2]. We further agree with Raffi et al.[1] that there has been a lack of consensus and consistency on the definition of nevirapine-HSR. In fact, Raffi et al.[1] acknowledge that no formal definition has been established for nevirapine-HSR. We respect their opinion that our chosen definition of nevirapine-HSR may be rather liberal compared to that of the European Summary Product Characteristics (SPC) [3] and the US Prescribing Information [4]. However, a review of the recent literature on the subject of nevirapine-HSR clearly illustrates that there is still little consistency in the definition of nevirapine-HSR [5–7]. Therefore, under these circumstances, our classification of nevirapine-HSR represents a reasonable and conservative compromise, within the constraints of our population-based database. Although Raffi et al.[1] are correct in their claim that the recommendation against the use of nevirapine in HIV/HCV-coinfected patients is not included in the DHHS, IAS or European guidelines, these guidelines do recommend close monitoring of transaminases and liver function tests when prescribing nevirapine to this population. Of note, the Therapeutic Guidelines for HIV-1 infected adults by the BC Centre for Excellence in HIV/AIDS, in Vancouver, Canada [8] include a recommendation against the preferential use of nevirapine among HCV/HIV infected individuals since October of 2006. This was almost 1 year before our article was published in AIDS. In conclusion, the relationship between nevirapine-based HSR and HCV co-infection resulting in an increased risk of mortality was clearly displayed in our study [2], suggesting that caution should be applied when using nevirapine in this population. As shown in table 3 from our study, the concurrent use of stavudine and didanosine, which were previously commonly used in combination with nevirapine in earlier treatment regimens, was not associated with non-accidental death. We agree with Raffi et al.[1] that appropriately powered studies with other antiretroviral drugs are needed to allow further conclusions to be made regarding the implication of our findings in comparable HIV/HCV co-infected populations.

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