Efavirenz and rifampicin: lower body weight associated with higher concentrations

Efavirenz-based regimens are recommended for treatment of HIV/TB coinfected patients, but the optimal dose (600 vs 800mg QD) remains unclear.

A poster from Lisa Almond and the Liverpool group presented findings from a retrospective survey of their TDM dataset, to determine plasma concentrations in patients receiving 600 or 800mg of efavirenz with rifampicin, for which samples were available 18 to 16 hours post dose.

Exclusions were <18years, pregnancy, incomplete information on weight and gender and possible non-adherence indicated by plasma concentrations <100ng/ml. Results were compared to 8 to 16 hours post dose samples from patients receiving efavirenz who were not taking TB treatment.

Evaluable data were available from 20 patients receiving 600mg efavirenz plus rifampicin, 111 patients receiving 800mg efavirenz plus rifampicin and 360 patients in the comparator group.

The investigators reported comparable efavirenz concentrations between doses in patients also taking rifampicin.

In the 800mg and rifampicin group they noted a trend towards higher numbers of patients weighing <60kg to have efavirenz concentrations considered to be in the toxic range (>4000ng/ml) compared to those above this weight (42.5 vs 25.3%, OR 1.12, p=0.09).

They also observed a significant association between weight and efavirenz concentrations in patients receiving 800mg and rifampicin in men (rho=-0.27, p=0.003) and women (rho=-0.15, p=0.004). There was however no gender difference in efavirenz concentrations in patients receiving 800mg efavirenz with rifampicin.

Nested logistic regression analysis confirmed weight (p=0.03) but not gender (p=0.71) or efavirenz dose (p=0.46) was significantly associated with efavirenz concentrations >4000ng/ml.

In their conclusion the investigators wrote this survey provides further evidence that one dose may not fit all in patients taking rifampicin. They also noted that data on ethnicity and CYP2B6 genotype were not captured in this analysis which are important determinants of efavirenz concentrations.

Almond L, Gibbons S, Davies G, et al. A retrospective survey of the Liverpool TDM service: factors influencing efavirenz concentrations in patients taking rifampicin. 6th International Workshop on Clinical Pharmacology of HIV Therapy. 28-30 April 2005. Quebec. Abstract 19.