The findings of this study also indicate that there is variation in the population in the degree of autoinduction. More than half of the study population showed no change in clearance within the first 2 weeks of treatment, and this finding corresponds to the results of Kappelhoff et al. [23]. For the group that exhibited autoinduction,

the findings were similar to those of Zhu et al. [8], with mean clearance increasing from 5.2 to 8.9L/h, values that correlate well with the finding by Zhu et al. of a mean change in clearance rate from 5.5 to 9.1 L/h between baseline and week 2 of treatment. These findings suggest that it should be possible to roughly categorize the African population into those who exhibit autoinduction and those who do not, which would have clinical implications, as the latter category IWR 1 of patients would experience check details efavirenz toxicity to a greater degree and for a longer period. However, as Kappelhoff et al. reported a 10% increase in clearance after 2 weeks of treatment in the same population that had no change in clearance within the first 2 weeks of treatment, we cannot conclude at this stage whether the latter group did not exhibit autoinduction at all, or if they exhibited it after 2 weeks of treatment. As observed previously, it was found

in this study that an initially high plasma concentration was not a key determinant of autoinduction. However, patients with a large increase in clearance within the study period showed relatively low steady-state efavirenz concentrations, with some showing subtherapeutic concentrations on day 14. This finding correlates with the finding of Ngaimisi et al. of subtherapeutic efavirenz concentrations in Tanzanian patients after 16 weeks

of treatment [32], which was related to autoinduction and CYP2B6 polymorphism. This finding suggests that autoinduction exposes a few individuals to a risk of virological failure among populations ifenprodil previously known for high plasma concentrations and adverse effects of efavirenz. Quarterly therapeutic drug monitoring of patients on efavirenz, as suggested by Pereira et al. [5], could play an important role in identifying such individuals and patients with nonadherence secondary to toxicity, especially in the African population where CYP2B6 polymorphism confers a risk of toxicity. The efavirenz-related adverse CNS symptoms recorded in this study are similar to those previously reported [33]; however, the frequency (69%) we observed was slightly higher than that previously reported (54%) [33,34]. This is probably related to the high frequency of CYP2B6 polymorphism in the African population [4,7], which has previously been associated with high efavirenz concentrations and related CNS symptoms [15,34].