Efavirenz dose reduction is safe in patients with high plasma concentrations and may prevent efavirenz discontinuations.
OBJECTIVE
To establish whether efavirenz dose reduction in patients with high plasma concentrations prevents toxicity-induced efavirenz discontinuations.


METHODS
HIV-infected patients with a high efavirenz plasma concentration (>or=4.0 mg/L) while using efavirenz 600 mg once daily as part of their highly active antiretroviral therapy regimen were selected from the AIDS Therapy Evaluation in The Netherlands cohort study. These patients were classified into 2 groups. The reduced-dose group contained all patients who underwent dose reduction after the high plasma concentration measurement; the standard-dose group consisted of patients who had no dose reduction. Kaplan-Meier and Cox proportional hazards analysis were used to assess the impact of dose reduction on toxicity-induced efavirenz discontinuations.


RESULTS
One hundred eighty patients with high plasma efavirenz levels were included, 47 of them subsequently had their efavirenz dose reduced from 600 mg to 400 mg once-daily, which resulted in a 41% decrease in the median efavirenz plasma concentration. At week 48, the Kaplan-Meier estimated cumulative incidence of toxicity-induced efavirenz discontinuations was 11.5% in patients who continued the standard dose versus 2.3% in patients who had a dose reduction; P = 0.066 (log-rank test). Dose reduction was not associated with loss of virological suppression.


CONCLUSIONS
Dose reduction may prevent toxicity-induced discontinuations in patients with high efavirenz plasma concentrations, whereas not compromising virological efficacy.
van Luin
Matthijs
M
Department of Clinical Pharmacy, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. m.vanluin@akf.umcn.nl
Gras
Luuk
L
Richter
Clemens
C
van der Ende
Marchina E
ME
Prins
Jan M
JM
de Wolf
Frank
F
Burger
David M
DM
Wit
Ferdinand W
FW
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D003521:Cyclopropanes; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009426:Netherlands; D010949:Plasma / Q000737:chemistry; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz