Featured news from NHIVNA
HIV-related news from NAM
Co-administration of rifampicin and efavirenz does not reduce efavirenz concentrations or efficacy
Lesley Odendal, 2012-07-24 15:10:00
Standard dosing of efavirenz, that was not adjusted for patient weight, resulted in therapeutic efavirenz concentrations and excellent virological outcomes in patients coinfected with TB and HIV who were also taking a rifampicin-containing TB treatment, according to results from the ACTG 5221 STRIDE study presented at the at the 19th International AIDS Conference (AIDS 2012) in Washington DC.
These findings have important implications for guidelines on rifampicin and efavirenz co-administration in TB/HIV co-infected patients. Rifampicin is known to cause drug-drug interactions, especially with efavirenz, which is recommended in first-line ARV treatment. Rifampicin co-administration is associated with an approximately 30% decrease in efavirenz trough concentrations (Cmin). Previous studies have showed that efavirenz dosing should be increased from the standard dose of 600mg to 800mg in TB/HIV patients who weigh more than 50kg when taking rifampicin; a recommendation which the Food and Drug Administration of the United States of America made in January this year.
Efavirenz concentrations were measured using high-performance liquid chromatography where the lower limits of quantification was defined as 1mg/l. Cmin samples were obtained 20to 28 hours after efavirenz administration. Efavirenz levels were evaluated at antiretroviral (ARV) treatment weeks 4, 8, 16 and 24 for those patients on rifampicin, and weeks 4 and 8 for those not on rifampicin. Samples were only collected in participants with no self-reported missed efavirenz or rifampicin doses in the previous three days.
According to Dr Annie Luetkemeyer, higher weight did not jeopardise efavirenz efficacy in patients taking rifampicin-containing TB treatment. In 505 patients who were taking both efavirenz and rifampicin, none reached below the minimum recommended plasma concentration of <1 mg/l of efavirenz. The median efavirenz Cmin was found to be 1.96 mg/l (IQR: 1.24 – 3.7).
Heavier patients did have significantly lower efavirenz concentrations, but only when heavier patients were defined as weighing 60kg or above. The median efavirenz Cmin in patients weighing below 50kg was 2.08 (IQR:1.33-4.33) compared to 1.86 (IQR:1.18-3.64) in those patients weighing 50kg and above (p=0.09). In contrast, the median efavirenz Cmin in patients weighing below 60kg was higher at 2.02 (IQR: 1.29-4.09) compared to 1.68 (IQR: 1.07-3.06) in those patients weighing 60kg and above (p=0.02).
When examining the efavirenz Cmin in patients also taking rifampicin compared to those who were not, there was no significant difference found across patient weight levels, except when disaggregated by race. There was a significant difference in efavirenz Cmin in black patients taking efavirenz with or without rifampicin. For the black patients taking rifampicin (n=367), the efavirenz Cmin level was 2.1 compared to those not taking rifampicin (n=269) whose efavirenz Cmin level was 1.8 (p=0.01). The researchers suggested that this paradoxical finding is likely to be due to genetic distinctions in metabolism in black patients. The study did not include enough members of other races to show significant differences.
Subtherapeutic efavirenz Cmin of less than 1 mg/l was not associated with rifampicin coadminstration, according to the study results. These showed that 27.3% on rifampicin (versus 26.2% not taking rifampicin) had an efavirenz Cmin less than 1mg/l and this finding was not found to be statistically significant (p=0.72).
Rates of HIV virological suppression were also found not to be reduced in patients above 50 kg or 60 kg taking efavirenz and rifampicin. The investigators concluded that these data do not support weight-based increase of efavirenz during rifampicin-containing TB treatment.
Source:1
