The Authors’ Reply

Excerpt

We appreciate the interest that Drs Leith, Hinzmann and Mayers took in our recent paper Practical Guidelines to Interpret Plasma Concentrations of Antiretroviral Drugs.[1] The purpose of this review was to provide a practical guide for therapeutic drug monitoring of antiretroviral drugs based on currently available literature data. For nevirapine a target trough level (C_trough) of >3.4 mg/L has been reported.[2] In some cases, however, when patients are treated with nevirapine at its registered dose of 200mg twice daily, the C_trough remains below 3.4 mg/L. This may be the result of multiple causes (e.g. adherence, comedication, clinical condition, treatment history). The interpretation of a patient’s drug level in such a case must be performed on an individual basis. When, however, all potential interfering causes have been ruled out and the patient does not exhibit signs of adverse effects we feel that the treating physician could consider a daily dose of 600mg with frequent safety monitoring. This consideration is based on the study results of González de Requenza et al.[3] They increased the daily dose of nevirapine from 400 to 600mg in 25 patients experiencing a first virological failure (>50 HIV RNA copies/mL). The patients were at least 3 months on a nevirapine containing triple combination. They concluded that this dose increase led to a significant rise in nevirapine plasma levels and was well tolerated. A greater virologic response was also noticed among the patients with higher nevirapine plasma concentrations.[3] Clearly this concerns results from a small study and more data should become available before this becomes ‘evidence-based medicine’. Dr Leith et al., thus, rightly point out that only for the daily nevirapine dose of 400mg a huge safety and efficacy database exists and evidently not for the 600mg dose. Hopefully further studies will be designed to find out whether the suggested dose increase is a safe and effective approach for patients with low nevirapine C_trough levels. …