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Efavirenz can be used at normal dose with rifampicin, Thais report
In people with lower body weight the use of efavirenz at the normal 600mg dose alongside the tuberculosis (TB) drug rifampicin does not appear to result in low efavirenz levels or HIV treatment failure, according to preliminary results of a randomised Thai study presented today at the Fifteenth International AIDS Conference in Bangkok.
Rifampicin reduces efavirenz total exposure (AUC) by an average of 26%, and given the wide variability of efavirenz plasma levels within the population, this drug interaction may expose a substantial number of patients to the risk of HIV treatment failure.
WHO treatment guidelines for resource-limited settings recommend efavirenz as first-line treatment for people with HIV/TB coinfection because the effect of rifampicin on alternative drugs such as nevirapine is more substantial, but the WHO guidelines suggest that it may be necessary to increase the efavirenz dose to 800mg per day. This has the effect of increasing the cost of treatment and increasing the pill burden for patients.
The study recruited 84 patients diagnosed with tuberculosis who had been receiving rifampicin-containing TB treatment for at least one month, and randomised the patients to receive efavirenz at 600mg (group A) or 800mg (group B).
The study was designed to determine whether patients who received the lower efavirenz dose achieved satisfactory plasma levels of the drug and whether any differences were apparent in response to treatment, measured as time to viral load below 50 copies/ml and CD4 count changes from baseline.
The mean body weight in both groups was around 50kg and body mass index was low (19 kg/m2). The median baseline CD4 cell counts were 29 (1, 224) cells/mm3 and 46 (0, 384) cells/mm3 in group A and B, respectively. There were no significant differences in baseline characteristics between the two groups.
Therapeutic drug monitoring took place at day 14, twelve hours after dosing. Median efavirenz levels were 3.02mg/l and 3.39mg/l in group A and B, respectively. Three patients in group A, but no patient in group B, had an efavirenz level below 1 mg/l (p = 0.347). Median time to virological success (HIV RNA <50 copies/ml) was 16 weeks in group A and 19 weeks in group B (p = 0.960). Median CD4 change from baseline to week 16 was 87.5 cells/mm3 in group A and 88.0 cells/mm3 in group B (p = 0.978). Central nervous system toxicity was found in 13 and 11 patients in group A and B, respectively (p = 0.675), but only one patient in group A had to discontinue efavirenz.
The study will continue for 48 weeks, but study investigators from Bangkok’s Ramathibodi Hospital told the conference that the preliminary results were promising. One caveat to this study that will require further investigation, warned experts in the audience, is the low average body weight of study participants. Numerous studies of plasma drug levels of HIV medications have shown, unsurprisingly, that people with lower body weight also have higher plasma drug levels because they have less body tissue to distribute drug across.
Reference
Manosuthi W et al. A randomized controlled trial of efavirenz 600 mg/day versus 800 mg/day in HIV-infected patients with tuberculosis to study plasma efavirenz level, virological and immunological outcomes: A preliminary result. XV International AIDS Conference, Bangkok, abstract MoOrB1013, 2004.
Rifampicin reduces efavirenz total exposure (AUC) by an average of 26%, and given the wide variability of efavirenz plasma levels within the population, this drug interaction may expose a substantial number of patients to the risk of HIV treatment failure.
WHO treatment guidelines for resource-limited settings recommend efavirenz as first-line treatment for people with HIV/TB coinfection because the effect of rifampicin on alternative drugs such as nevirapine is more substantial, but the WHO guidelines suggest that it may be necessary to increase the efavirenz dose to 800mg per day. This has the effect of increasing the cost of treatment and increasing the pill burden for patients.
The study recruited 84 patients diagnosed with tuberculosis who had been receiving rifampicin-containing TB treatment for at least one month, and randomised the patients to receive efavirenz at 600mg (group A) or 800mg (group B).
The study was designed to determine whether patients who received the lower efavirenz dose achieved satisfactory plasma levels of the drug and whether any differences were apparent in response to treatment, measured as time to viral load below 50 copies/ml and CD4 count changes from baseline.
The mean body weight in both groups was around 50kg and body mass index was low (19 kg/m2). The median baseline CD4 cell counts were 29 (1, 224) cells/mm3 and 46 (0, 384) cells/mm3 in group A and B, respectively. There were no significant differences in baseline characteristics between the two groups.
Therapeutic drug monitoring took place at day 14, twelve hours after dosing. Median efavirenz levels were 3.02mg/l and 3.39mg/l in group A and B, respectively. Three patients in group A, but no patient in group B, had an efavirenz level below 1 mg/l (p = 0.347). Median time to virological success (HIV RNA <50 copies/ml) was 16 weeks in group A and 19 weeks in group B (p = 0.960). Median CD4 change from baseline to week 16 was 87.5 cells/mm3 in group A and 88.0 cells/mm3 in group B (p = 0.978). Central nervous system toxicity was found in 13 and 11 patients in group A and B, respectively (p = 0.675), but only one patient in group A had to discontinue efavirenz.
The study will continue for 48 weeks, but study investigators from Bangkok’s Ramathibodi Hospital told the conference that the preliminary results were promising. One caveat to this study that will require further investigation, warned experts in the audience, is the low average body weight of study participants. Numerous studies of plasma drug levels of HIV medications have shown, unsurprisingly, that people with lower body weight also have higher plasma drug levels because they have less body tissue to distribute drug across.
Reference
Manosuthi W et al. A randomized controlled trial of efavirenz 600 mg/day versus 800 mg/day in HIV-infected patients with tuberculosis to study plasma efavirenz level, virological and immunological outcomes: A preliminary result. XV International AIDS Conference, Bangkok, abstract MoOrB1013, 2004.
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