Important note: Information in this article was accurate in June 2005. The state of the art may have changed since the publication date.
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HIV Treatment Bulletin - Vol. 6, No. 6, June 2005
Simon Collins, HIV i-Base
Several studies have previously reported extremely high levels of efavirenz in African women, and this has been linked with discontinuation related to CNS side effects.
A case report from Liverpool University, detailed the response of a 40 year old Zambian women, diagnosed in June 2004 with a CD4 count of 34 cells/mm3, who was started on AZT/3TC/efavirenz. [1] Five-drug rifampicin-based treatment for pulmonary TB was started 2 months later, and the dose of efavirenz was increased to 800mg daily.
Drug level monitoring (TDM) two weeks after initiation of TB treatment, showed EFV trough levels around 27,500 ng/ml (minimum effective target =1,000 ng/mL; maximum target = 4,000 ng/mL). Although no neurological side effects were reported, EFV dose was reduced to 600mg/day. Drug levels two weeks later had increased to almost 44,500 ng/mL and efavirenz was stopped. At this point she appeared vague, confused and was unsteady on her feet, while MRI brain scan was normal.
The authors commented that EFV levels were still at toxic levels two weeks after discontinuation of treatment, and that TDM had been vital to enable correct management.
A second poster at the meeting presented results from a retrospective survey of the Liverpool TDM database of patients from 1999-2004 who had used efavirenz at a dose of either 600mg (n=20) or 800mg (n=125) while taking rifampicin. [2]
They reported a large interpatient variability in drug levels that resulted in no statistically different percentages of patients below the minimum target level, or above the maximum target level.
References:
| 1. | Crowe G, Khoo SH. Toxic levels of efavirenz (EFV) two weeks after stopping therapy. BHIVA Conf 2005 Apr 20-23;11: Abstract No. P61. |
| 2. | Gibbons S, Almond L, Back D et al. Efavirenz concentrations resulting from co-administration of rifampicin with either 600 or 800mg efavirenz. BHIVA Conf 2005 Apr 20-23;11: Abstract No. P33. |
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