800mg efavirenz may not be needed with rifampicin-based TB regimens, especially in African patients

29 March 2005. Related: Conference reports, TB coinfection, HIV 7th Glasgow 2004.

Graham McKerrow, HIV i-Base

A team of London doctors reported on a case series of 8 patients with HIV and tuberculosis who developed significant toxicity while taking a high dose of efavirenz (800mg QD) with rifampicin. They concluded that such a treatment regimen could not be universally endorsed, and may raise particular concerns in African patients. [1]

Paul Brennan-Benson and colleagues at St George’s Hospital, London, collected data on the demographics, efavirenz levels and clinical outcomes in the six women and two men. They reported that 7 patients developed significant central nervous system side effects, ranging from anxiety to delirium, and one developed efavirenz-induced hepatitis. All 8 patients had high trough levels of efavirenz: median 19,551 mg/mL (range 5201 – 19,591; target >1000ng/dL). Median CD4 count on starting HAART was 77 cells/mm³ (range 25-668).

Four patients tolerated lower doses of 400-600mg QD and achieved viral load suppression to less than 50 copies/mlL and three switched from efavirenz to other regimens. One patient died as a result of complications brought on by TB.

Previous data have suggested that CYP2B6 variant is more common in African people and may be associated with delayed efavirenz clearance and the researchers write that this might explain the high levels of the drug observed in these cases.

The authors concluded by saying therapeutic drug monitoring may have a useful role to play in minimising side effects.

Comment

A report from the Bangkok conference in Thai patients suggested that the increased efavirenz dose may also not be required in patients with low body weight (<50kg). [2]

References:

1. Brennan-Benson P, Lyas R, Pakianathan M et al. High dose efavirenz with rifampicin for HIV infected patients with concomitant tuberculosis: one size does not fit all. 7th ICDTHI,14-18 Nov, 2004, Glasgow. Abstract P194.
2. Efavirenz interaction with rifampin may not require dose adjustment in patients with low body weight. HIV Treatment Bulletin Vol 5 No 7, Aug/Sep 2004.