Telaprevir (TVR) was approved by the FDA in May 2011 for the treatment of hepatitis C. This protease inhibitor converts into two diastereomers with significant difference in antiviral activity. Clinical efficacy has been correlated with serum concentrations. Therefore, a sensitive and selective high-performance liquid chromatographic method for the simultaneous determination of both clinically relevant diastereomers of TVR was developed. Linearity ranged from 20 to 10,000 ng/mL. The coefficients of variation were <7.3%, and accuracy was between −4.0 and 5.4%. In 105 clinical samples, both diastereomers of TVR had a high degree of correlation to each other, but concentrations showed a broad range and an increase during therapy.

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Background Broad use of tenofovir and an ageing HIV-infected population have created an interest in renal function in HIV patients. Serum cystatin C is a newer marker of renal function and might be more sensitive than creatinine. Methods Patients were enrolled consecutively in an observational study. HIV-seropositive patients naive to antiretroviral therapy ( n=261) were compared with healthy volunteers undergoing check-up procedures ( n=193). Estimated glomerular filtration rate (eGFR) was derived using creatinine-based Modification of Diet in Renal Disease (MDRD) and Cockcroft–Gault formulas or cystatin C-based calculations. HIV-seropositive patients starting antiretroviral therapy ( n=92) were followed prospectively after enrolment. Results MDRD showed a higher median eGFR in antiretroviral- naive HIV-seropositive patients compared with controls (104 versus 93 ml/min; P<0.001). Cockcroft–Gault gave similar results (118 versus 106 ml/min; P<0.001). By contrast, cystatin C levels in HIV-seropositive individuals were higher, resulting in a lower median eGFR compared with controls (99 versus 120 ml/min; P<0.001). Cystatin C was positively correlated with HIV RNA ( r=0.33, P<0.01) and inversely correlated with CD4+ T-cell count ( r=-0.29, P<0.01). Initiating antiretroviral therapy ( n=92) decreased cystatin C levels and led to an increased cystatin C-based eGFR from median 84 to 103 ml/min at week 24 ( P<0.001). Serum creatinine was not substantially altered. Conclusions Correlation of cystatin C with HIV RNA and CD4+ T–cell count, plus decrease of cystatin C after suppression of HIV replication, suggest an increase of cystatin C levels by active HIV infection. This might result in overestimation of renal impairment, particularly in treatment-naive patients. Therefore, use of cystatin C to calculate GFR in HIV-seropositive individuals should not be recommended without further validation.

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