Background and objective. Detrimental bidirectional pharmacokinetic interactions have been observed when telaprevir (TVR) and ritonavir-boosted HIV protease inhibitors are coadministered in healthy volunteers. This study aimed to evaluate the role of ritonavir in the bidirectional TVR and atazanavir interactions. Method. Open-label, sequential study carried out in HCV/HIV-coinfected subjects on a ritonavir-boosted atazanavir-based (ATVr) antiretroviral regimen (300/100 mg q24 h) and triple therapy for chronic C hepatitis genotype 1 (TVR, 1125 mg q12 h, pegylated interferon-α and ribavirin). Pharmacokinetic profiles were acquired before and after switching from ATVr to un-boosted atazanavir (ATV) (200 mg q12 h). The plasma levels of both drugs were determined by LC/MS. Pharmacokinetic parameters were calculated by non-compartmental analysis and compared by geometric mean ratios and their 90% confidence intervals. Results. Fourteen Caucasian HCV/HIV-coinfected males were enrolled in this study. After the ritonavir was withdrawn, the TVR AUC0-12, Cmax and Cmin values increased by 19% (7-30%), 12% (0.9-29%) and 18% (2-34%), respectively, without any changes in the TVR terminal half-life. The ATV AUC0-12, Cmax and Cmin values were a 39% (13-66%), 19% (8-59%) and 48% (1-96%) higher, respectively, with a significantly shorter terminal half-life (22.6 vs. 10.4 hours). Conclusions. Ritonavir is responsible for the adverse interactions between TVR and ATVr, possibly by influencing either the absorption phase or first-pass metabolism of TVR. The boost effect of TVR on ATV exposure is higher than ritonavir, despite having a shorter terminal half-life. The coadministration of TVR and un-boosted ATV results in increased exposure of both drugs compared to their coadministration with ritonavir.