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Therapeutic drug monitoring (TDM) enables efavirenz dose reduction in virologically-controlled patients
A. Calmy1, A. Fayet2, M. Cavassini3, T. Buclin2, T. Dang3, M.-P. Schneider4, A. Telenti5, G. Eperon1, L.A. Decosterd2, B. Hirschel1, For the Swiss HIV Cohort Study
1Geneva University Hospital, HIV Unit, Geneva, Switzerland, 2Division of Clinical Pharmacology, University Hospital Lausanne, Lausanne, Switzerland, 3Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland, 4Policlinique Médicale Universitaire, University Hospital Lausanne, Lausanne, Switzerland, 5Institute of Microbiology, University Hospital Lausanne, Lausanne, Switzerland
Background: Benefits of adjusting dosage in patients treated with efavirenz (EFV) may include better control of neuropsychiatric symptoms. We tested a simplified Bayesian algorithm to guide efavirenz dose reduction in patients having EFV trough concentration above 4000 µg/L (percentile 75 [P75] under 600 mg q.d.), with documented virological efficacy.
Methods: This prospective 6-months open-label multicenter study included successive consenting participants with EFV concentration extrapolated to exceed 4000 µg/L on trough and undetectable HIVRNA (< 40 copies/mL). Adherence was assessed electronically by Medication Event Monitoring System (MEMS®). Primary endpoint was the number of patients with plasma concentrations reaching the therapeutic targets (1000-4000 µg/L) at 3 and 6 months.
Results: Fifteen participants (53% male, median weight 67.5 kg [IQR 58-76], CD4 count 479 [IQR 374-554]) were included. Median baseline EFV concentration was 8409 µg/L [6610-10370], 33% between P75 and P95 qualifying for a 400 mg EFV dose, and 67% above P 95, qualifying for a 200 mg EFV dose. Ten patients have now completed their dose reduction cycle, reaching EFV plasma concentrations between 1000 and 4000 µg/L at 3 months (median 2856 µg/L [2192-3157]). Six were steady at 6 months (2890 µg/L [2576-3199]) (figure 1). Mean adherence was 98% (SD ±2.0%) for all patients included in a cycle of dose reduction. All patients remained with undetectable HIV-RNA at 3 and 6 months.
[Figure: Evolution of plasma concentrations in patients with EFV dose reduction]
Conclusion: TDM-guided efavirenz dose reduction was successful and safe over a 10 to 24-week period. A single cycle of dose reduction led EFV plasma concentrations into the recommended therapeutic interval of 1000-4000 µg/L, without compromising virological suppression.
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