Important note: Information in this article was accurate in August 2004. The state of the art may have changed since the publication date.
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HIV Treatment Bulletin - Vol. 5, No. 7, August/September 2004
Simon Collins, HIV i-Base
Treatment guidelines for patient requiring treatment for both HIV and TB currently recommend increasing the dose of efavirenz from 600mg to 800mg daily in patients using rifampin-based TB regimens. This has difficult logistic and cost implications especially for treatment in patients using WHO-recommended fixed-dose combinations that include efavirenz. These recommendations are based on pharmacokinetic interaction studies.
Manosuthi and colleagues from Mahidol University, Bangkok presented results from the first clinical trial comparing 600mg to 800mg efavirenz (with d4T and 3TC) in patients on stable rifamicin treatment. Plasma efavirenz level was measured (at 12 hours after dosing, on day 14) by HPLC. CD4 and HIV RNA were assessed at 16, 24, 36, and 48 weeks.
Preliminary results of 70 patients (37 in group A and 33 in group B) were presented. The follow-up period ranged from 16 to 36 weeks. The groups were evenly balanced on all important baseline characteristics. Mean body weight and BMI was about 50 kg and 19 kg/m2. Median baseline CD4 counts were 29 (range; 1, 224) cells/mm3 and 46 (0, 384) cells/mm3 in group A and B, respectively. Median efavirenz levels were 3.97 mg/L (0.07, 12.21) and 3.39 mg/L (1.03, 21.31) in group A and B, respectively. Three patients in group A, but no patient in group B, had efavirenz level <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 increase from baseline to week 16 was around +898 cells/mm3 in each arm.
CNS toxicity was found in 13 and 11 patients in groups A and B, respectively (p = 0.675). One patient in group A had to discontinue efavirenz.
Ref: Manosuthi W, Sungkanuparph S, Vibhagood A, et al. A randomised 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. Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. MoOrB1013.
Comment
Although median efavirenz levels were similar in each group, the range varied considerably. There is an obvious concern for the three patients in arm A with very low levels. As weight is referred to in the study it will be interesting to see any correlation between weight and drug levels in the final analysis. This is clearly a factor in Asia and often in Africa.
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