Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti–hepatitis C virus activity in vitro . Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log10 after a 14-day oral treatment with 1200 mg twice daily ( P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025–treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 ± 6 (standard error) ng/mg protein (baseline) to 5 ± 1 ng/mg protein at day 15 ( P < 0.01). Conclusion: Debio-025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti–hepatitis C drugs.

Present and future possibilities for early diagnosis of hepatocellular carcinoma

BACKGROUND: In the combined antiretroviral therapy (cART) era, non–acquired immunodeficiency syndrome (AIDS)‐defining malignancies account for more morbidity and mortality in human immunodeficiency virus‐infected patients than AIDS‐defining malignancies. However, conflicting data have been reported on the relationship between immunodeficiency and the development of some non–AIDS‐defining malignancies.METHODS: A total of 14,453 patients from the prospective, multinational EuroSIDA cohort were included. Malignancies were classified as virus‐related, non–virus‐related epithelial, and other. The incidence of non–AIDS‐defining malignancies was calculated stratified by current CD4 count. Poisson regression was used to investigate factors associated with the development of non–AIDS‐defining malignancies.RESULTS: A total of 356 non–AIDS‐defining malignancies occurred, with an incidence rate of 4.3 per 1000 person years of follow‐up (95% confidence interval [CI], 3.8‐4.7); 172 (48.3%) were virus‐related, 135 (37.9%) were non–virus‐related epithelial, and 49 (13.7%) were classified as other. Anal (69 cases), lung (31 cases), and melanoma (13 cases), respectively, were the most common non–AIDS‐defining malignancies within each group. After adjustment, current CD4 was associated with virus‐related non–AIDS‐defining malignancies (incidence rate ratio [IRR], 0.81 per doubling; 95% CI, 0.75‐0.88; P < .0001) and non–virus‐related epithelial non–AIDS‐defining malignancies (IRR, 0.84; 95% CI, 0.75‐0.95; P = .004), but not with other non–AIDS‐defining malignancies (IRR, 1.04; 95% CI, 0.83‐1.31; P = .73). Current CD4 count was also associated with anal cancer (IRR, 0.86; 95% CI, 0.75‐0.99; P = .03), Hodgkin lymphoma (n = 52; IRR, 0.83; 95% CI, 0.73‐0.95; P = .005), and lung cancer (IRR, 0.76; 95% CI, 0.64‐0.90; P = .0002).CONCLUSIONS: A low current CD4 count was associated with an increased incidence of certain non–AIDS‐defining malignancies. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non–AIDS‐related malignancies. A randomized trial to explore this strategy is urgently needed. Cancer 2010. © 2010 American Cancer Society.