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 log 10 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. (HEPATOLOGY 2008; 47:817-826.)

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Considering the high proportion of patients who objected to having LP performed in the absence of neurological symptoms and the risk associated with this procedure, it may be preferable to use treatments with good CNS penetration in all HIV-positive patients with early syphilis.

Introduction Delay in HIV diagnosis and consequently late care entry with low CD4 counts remain a major challenge for the control of the HIV/AIDS epidemic. The aim of this study was to analyse the evolution of characteristics of the HIV epidemic in Poland. Methods Cross‐sectional data were collected for 3972 HIV‐infected patients followed up in 14 of 17 Polish HIV treatment centres in the years 2000–2015. Clinical data were analysed and factors associated with late presentation (baseline CD4 count < 350 cells/μL or history of AIDS‐defining illness) and advanced HIV disease (baseline CD4 count < 200 cells/μL or history of AIDS) were identified. Results The majority (57.6%) of patients entered care late, while 35.6% presented with advanced HIV disease. The odds of being linked to care late or with advanced HIV disease increased consistently across age categories, increasing from 2.55 [95% confidence interval (CI) 1.46–4.47] for late presentation and 3.13 (95% CI 1.49–6.58) for advanced disease for the 21–30‐year‐old category to 5.2 (95% CI 1.94–14.04) and 8.15 (95% CI 2.88–23.01), respectively, for individuals > 60 years of age. Increased risks of late entry and advanced HIV disease were also observed for injecting drug users [adjusted odds ratio (aOR) 1.74 (95% CI 1.16–2.60) and 1.55 (95% CI 1.05–2.30), respectively], with lower aOR associated with the men who have sex with men transmission route [aOR 0.3 (95% CI 0.31–0.59) and 0.39 (95% CI 0.29–0.53), respectively]. The frequencies of cases in which patients were linked to care late and with advanced HIV disease decreased over time from 67.6% (2000) to 53.5% (2015) (P < 0.0001) and from 43.5% (2000) to 28.4% (2015) (P = 0.001), respectively. Conclusions Despite improvements over time, most patients diagnosed with HIV infection entered care late, with a third presenting with advanced HIV disease. Late care entry remains common among people who inject drugs and heterosexual groups.

Introduction: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression.Methods: Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients’ characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used.Results: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01–2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08–2.01), p = 0.016], baseline lymphocyte CD4 count ≥200 cells/µL [OR:1.72 (95%CI:1.04–2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29–2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL [OR:2.08 (95%CI:1.01–4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52–5.26), p = 0.001].Conclusions: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions.