A pharmacokinetic study in healthy volunteers was reminiscent of the saquinavir study, and was terminated early because of high rates of severe transaminitis [101]. Recent data suggest that atazanavir with or without ritonavir boosting had unfavourable pharmacokinetics when administered with rifampicin [102–104]. Trough atazanavir ZD1839 molecular weight concentrations were reduced by >80% [103]. Tipranavir concentrations were reduced by 80% by rifampicin [105]. The interaction between darunavir and rifampicin has not yet been investigated. In line with other PIs, it is currently recommended that darunavir should not be coadministered with rifampicin. The use of

rifabutin in treating TB in HIV-positive patients is discussed above (see ‘Use of rifapentine’ [EII]). Rifabutin can be administered Veliparib order with unboosted PIs except saquinavir [106], although they will rarely be used in practice. The balance between rifabutin induction and PI inhibition of CYP3A4 means that the dose of rifabutin should be decreased from 300 to 150 mg daily to avoid toxicity [48,70]. If PIs are used with low-dose ritonavir boosting then the dose of rifabutin should be reduced to 150 mg three times per week [49,105]. This recommendation

is derived from pharmacokinetic studies and modelling. There are no clinical outcome data for either HIV or TB using this strategy. Adherence should be monitored closely as the dose of rifabutin would become inadequate if the boosted PI is not taken concomitantly. Where available, drug levels of the PI should be measured. There have been reports of acquired rifabutin resistance occurring even in patients taking rifabutin 150 mg three

times a week with boosted PIs. No rifabutin drug levels were available in those patients and, although there may have been other reasons for these failures, physicians may consider measuring the levels of rifabutin and its active metabolite 25-0-desacetyl rifabutin if results are available in a timely manner [107]. Complex Cell press interactions may occur when a rifamycin is given with salvage regimens such as an integrase, boosted PI and an NNRTI. Rifabutin is safer than rifampicin, but there are few data to guide the clinician regarding dose modification. TDM is recommended. We recommend that PI/ritonavir combinations should not be given with rifampicin. [EII] If possible, the HAART regimen should be changed to avoid PIs. If effective HAART necessitates the use of PIs then rifabutin should be used instead of rifampicin. [AII] Raltegravir is metabolized by UGT1A1 glucuronidation. Rifampicin is an inducer of UGT1A1, and reduces trough levels of raltegravir by approximately 60% [108]. Because the antiviral activity of raltegravir 200 mg twice daily was very similar to that of the licensed dose (400 mg twice daily), an earlier recommendation was that standard doses of raltegravir should be used with rifampicin. There is at least one report of raltegravir failure when given like this with rifampicin (S.