OBJECTIVE: Many HIV-patients have a chronic liver disease due to HBV-/HCV-coinfections and/or consume of alcohol. In these patients therapy with EFV is often problematic because of NNRTI associated liver toxicity. Measurement of EFV plasmalevels and dose adjustment using TDM should be evaluated in this study. METHODS: EFV-plasmasamples were standardized drawn 12h after ingestion. Measurement of 576 EFV plasmalevels was performed by HPLC. EFV plasmalevels as well as ALT-, AST- and GGT-values of 64 patients treated with EFV (5206 weeks) were measured regularly. 16 patients had a HCV-coinfection, 3 had a HBV-coinfection and 5 had an concomitant alcoholic liver disease. Maximal changes of ALT-, AST- and GGT-values (DeltaALT, DeltaAST, DeltaGGT), CD4-/CD8 cells and HIV-RNA were registered during therapy. Dose adjustment was performed for EFV plasmalevels out of target range 1000-4000 ng/ml. RESULTS: EFV plasmalevels of 40 HIV-patients (2288 +/- 1199 ng/ml) showed no significant differences compared to plasmalevels of HIV/HCV-patients (2391 +/- 976 ng/ml) or to plasmalevels of HIV/HBV-patients (1913 +/- 288 ng/ml) or to those of HIV-patients with alcoholic liver disease (1702 +/- 506 ng/ml). In 24 HIV-patients with underlying liver disease median DeltaGGT was +25 IU/l, median DALT was +13 IU/l and median DeltaAST was +8 IU/l. Dose adjustment was performed in 1 patient during study period. Increasing rates of ALT-, AST- and GGT-values showed no significant differences between liver healthy HIV-patients and those with a liver disease. 44 patients with continuous EFV plasmalevels in target range reached a viral suppression <100 c/ml during therapy. CONCLUSIONS: EFV-plasmalevels of HIV-infected patients showed no significant differences compared to EFV-plasmalevels of coinfected patients with concomitant liver disease. In those patients DeltaALT, DeltaAST and DeltaGGT were not significantly different than in liver-healthy HIV-patients with normal EFV-plasmaconcentrations. EFV plasmalevels in target range of 1000-4000 ng/ml correlate to a good viral response. One patient after dose adjustment was able to continue therapy. Using TDM EFV therapy in patients with underlying liver disease is save.
OBJECTIVE: Many HIV-patients have a chronic liver disease due to HBV-/HCV-coinfections and/or consume of alcohol. In these patients therapy with EFV is often problematic because of NNRTI associated liver toxicity. Measurement of EFV plasmalevels and dose adjustment using TDM should be evaluated in this study. METHODS:EFV-plasmasamples were standardized drawn 12h after ingestion. Measurement of 576 EFV plasmalevels was performed by HPLC. EFV plasmalevels as well as ALT-, AST- and GGT-values of 64 patients treated with EFV (5206 weeks) were measured regularly. 16 patients had a HCV-coinfection, 3 had a HBV-coinfection and 5 had an concomitant alcoholic liver disease. Maximal changes of ALT-, AST- and GGT-values (DeltaALT, DeltaAST, DeltaGGT), CD4-/CD8 cells and HIV-RNA were registered during therapy. Dose adjustment was performed for EFV plasmalevels out of target range 1000-4000 ng/ml. RESULTS:EFV plasmalevels of 40 HIV-patients (2288 +/- 1199 ng/ml) showed no significant differences compared to plasmalevels of HIV/HCV-patients (2391 +/- 976 ng/ml) or to plasmalevels of HIV/HBV-patients (1913 +/- 288 ng/ml) or to those of HIV-patients with alcoholic liver disease (1702 +/- 506 ng/ml). In 24 HIV-patients with underlying liver disease median DeltaGGT was +25 IU/l, median DALT was +13 IU/l and median DeltaAST was +8 IU/l. Dose adjustment was performed in 1 patient during study period. Increasing rates of ALT-, AST- and GGT-values showed no significant differences between liver healthy HIV-patients and those with a liver disease. 44 patients with continuous EFV plasmalevels in target range reached a viral suppression <100 c/ml during therapy. CONCLUSIONS:EFV-plasmalevels of HIV-infectedpatients showed no significant differences compared to EFV-plasmalevels of coinfectedpatients with concomitant liver disease. In those patients DeltaALT, DeltaAST and DeltaGGT were not significantly different than in liver-healthy HIV-patients with normal EFV-plasmaconcentrations. EFV plasmalevels in target range of 1000-4000 ng/ml correlate to a good viral response. One patient after dose adjustment was able to continue therapy. Using TDM EFV therapy in patients with underlying liver disease is save.