Other studies have also shown 800 mg to be effective and safe [71,74]. In contrast, other BAY 80-6946 order data support using standard-dose efavirenz. In some cohort studies (in which most participants had a low body weight), 600 mg efavirenz has been given with rifampicin without lower drug exposure or compromised clinical efficacy [75,76]. In one study, efavirenz levels were not predicted by weight or gender and were not associated with HIV clinical outcomes, even though half the cohort had concentrations below the expected therapeutic range (1000–4000 ng/mL). This, as well as other studies, confirms the large interpatient variability in efavirenz levels
. In one study of Black South Africans taking rifampicin, no difference was seen in mid-dose efavirenz levels between patients on efavirenz 800 mg (n=31)
and those on efavirenz 600 mg (n=29) . This finding may be the result of a high frequency of polymorphisms in CYP450 2B6, which occur with a rate of 20% in the Black population compared with 3% in the White population [79,80]. The frequency of polymorphisms in CYP2B6 may also explain high rates of clinical toxicity in some studies . Recommendation [AII]: Patient under 60 kg: Use efavirenz 600 mg once daily (od). It should be made clear to patients that they may need an extra 200 mg efavirenz in addition to Atripla. Rifampicin and nevirapine are both used widely in resource-poor countries because they are cheap and readily available. There are data indicating that nevirapine levels are reduced by 20–55% by rifampicin [82–87]. PLX4032 Selleck Rucaparib The World Health Organization (WHO) suggest that no ‘lead-in’ period for nevirapine is needed if the patient is already on rifampicin – but they give no recommendation rating for this strategy. To overcome the problem of low nevirapine levels
with rifampicin, one trial administered 400 mg nevirapine as lead-in dose, increasing to 600 mg . The pharmacokinetics were satisfactory but there was a high incidence of nevirapine hypersensitivity during the dose escalation period. Two cohort studies have shown high rates of HIV viral suppression with standard-dose nevirapine and rifampicin [83,89]. However, in a recent study of 1283 patients starting HAART while on rifampicin, 209 people on nevirapine and 1074 on efavirenz, virological failure rates were higher, with an odds ratio of 2.9 [95% confidence interval (CI) 1.8–4.7] in the nevirapine arm vs. the efavirenz or not-on-TB-treatment arm . We recommend that, where alternatives exist, rifampicin should not be used with nevirapine. [DII] If there are no alternatives to using nevirapine with rifampicin, then normal doses should be used and TDM performed. No data are available and no studies are planned. It is thought that they should not be coadministered.