JAC Advance Access originally published online on October 10, 2006
Journal of Antimicrobial Chemotherapy 2006 58(6):1299-1302; doi:10.1093/jac/dkl399
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Administration of efavirenz (600 mg/day) with rifampicin results in highly variable levels but excellent clinical outcomes in patients treated for tuberculosis and HIV
1 Yale University, New Haven CT, USA 2 University of Liverpool Liverpool, UK 3 Nelson R Mandela School of Medicine University of KwaZulu Natal, Durban, South Africa
Received 22 June 2006; returned 10 August 2006; revised 7 September 2006; accepted 10 September 2006
*Corresponding author. Yale University School of Medicine AIDS Program, 135 College Street, Suite 323, New Haven, CT 06510-2483, USA. Tel: +1-203-688-6959; Fax: +1-203-737-4051; E-mail: Gerald.friedland{at}yale.edu
Objectives: Pharmacokinetic interactions between rifampicin and antiretroviral therapy (ART), including efavirenz, are problematic and need to be better defined to determine proper dose and to be correlated with short-term and long-term clinical outcomes.
Patients and methods: Consenting patients with smear-positive pulmonary TB and HIV received once daily didanosine + lamivudine + efavirenz (600 mg), with rifampicin-containing TB regimen by directly observed therapy and self-administration at TB therapy completion. Trough efavirenz levels were measured by HPLC at 1, 2, 4 and 6 months while on rifampicin and after discontinuation. HIV and TB outcomes were monitored.
Results: Twenty African patients were enrolled [15 female, mean age 31 years, baseline weight 59.4 kg (range 45–97), viral load 5.75 log10 copies/mL and CD4 230 cells/mm3]. Seventy-two efavirenz concentrations were available from 19 patients (58 on, 14 after rifampicin). The geometric mean efavirenz concentration was 1730 ng/mL (range 354–27 179) on and 1377 ng/mL (range 572–3975) off rifampicin (P = 0.55). Inter-subject variability in efavirenz concentrations was greater on rifampicin (CV 157% versus 58% off) with relatively consistent intra-subject variation over time (median CV 24%). Over half of patients had efavirenz concentrations above or below the expected therapeutic range (1000–4000 ng/mL). Efavirenz levels were not predicted by weight or gender and were not associated with HIV clinical outcomes. Overall 80% of patients had non-detectable viral loads at 6 months and 65% at 21 months with a cumulative CD4 cell increase of 196 cells/mm3.
Conclusions: In this longitudinal study, despite wide variability in plasma efavirenz concentrations during rifampicin administration, excellent clinical outcomes were obtained. In African patients treated for HIV and TB, our data support the routine use of efavirenz at 600 mg/day when receiving rifampicin.
Keywords: antiretroviral therapy , drug interactions , TB
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