Efavirenz plasma levels for the prediction of treatment failure in heavily pretreated HIV-1 infected patients.
OBJECTIVE
Efavirenz (EFV) plasma levels have been discussed as a predictor of treatment failure in HIV infected patients. The aim of this prospective, open-labeled, case-control study was to evaluate pretreated patients in regards to efavirenz plasma levels and efficacy of therapy.


METHODS
Blood samples were obtained monthly from 33 patients receiving efavirenz in combination with other antiretroviral agents for at least 3 months. EFV plasma concentrations and potease inhibitor (PI) plasma levels were measured by high-performance liquid chromatography (HPLC). EFV plasma levels were correlated with efficacy. In patients with virologic failure genotypic resistance testing was performed.


RESULTS
Mean efavirenz plasma levels (n = 240) of 33 patients were 3.119 +/- 2.497 ng/ml. There were no significant differences between median efavirenz plasma levels of 24 patients (72%) with a HIV-RNA < 20 copies/ml (2.168 ng/ml), 3 patients with HIV-RNA of 20 500 copies/ml (3.362 ng/ml), and 6 patients with a virologic failure (>500 copies/ml) (2.190 ng/ml) respectively. Efavirenz plasma levels below 1.000 ng/ml were found in 4/27 effective treated patients, and in 4/6 patients with virologic failure. In all patients with virologic failure multiple NRTI, NNRTI and PI mutations were found in genotypic resistance testing.


CONCLUSIONS
An individual EFV plasma level below 1.000 ng/ml in one single measurement seems to be predictive of viral failure and the developement of genotypic resistance. Therapeutic drug monitoring of EFV might be helpful, especially in heavily pretreated patients, to reach long term sufficently effectiveness of therapy.
Langmann
P
P
University of Wuerzburg, Division of Infectious Diseases, Medical Policlinic, Germany. p.langmann@medizin.uni-wuerzburg.de
Weissbrich
B
B
Desch
S
S
Väth
T
T
Schirmer
D
D
Zilly
M
M
Klinker
H
H
D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D048588:Benzoxazines; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D010078:Oxazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011379:Prognosis; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D017211:Treatment Failure
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz