49 research outputs found
Minor mutations in HIV protease at baseline and appearance of primary mutation 90M in patients for whom their first protease-inhibitor ntiretroviral regimens failed
The association between minor mutations in human immunodeficiency
virus (HIV) protease at baseline and development
of common primary mutation 90M at virological failure (conferring
some resistance to all protease inhibitors [PIs]) was
evaluated in 93 previously drug-naive patients experiencing
failure of their first PI-based antiretroviral regimens. In logistic
regression analysis, the probability of accumulating a new 90M
mutation at virological failure was associated with the presence
at baseline of minor mutation 36I (naturally occurring in
∼25% of HIV clade B and in >80% of HIV non-clade-B viruses)
(adjusted odds ratio, 13.5 [95% confidence interval, 1.89–95.6];
P=.009) and, possibly, of 10I/V. This suggests a potential role
for the presence of 36I at baseline in predicting the appearance
of 90M at virological failure
Impact of antiretroviral dosing and daily pill burden on viral rebound rates in naive patients receiving a tenofovir-based regimen
Methods A total of 480 ART-naive patients were selected from the GNOMO cohort. Incidence rate of viral rebound (VR = first of two consecutive VL>50 cp/ml) was calculated as number of events over PYFU and expressed at univariate and multivariate analysis as incidence rate ratio (IRR). Number of both pills and doses per day were used to define three different types of regimens: twice-a-day regimens (BID regimens); once-a-day regimens with 3 pills (high-pill QD [hp-QD]). Adjusted rates of viral rebound were estimated by Poisson regression using date of first HIV-RNA <50 c/ml as baseline. Follow-up was censored at the date of VR, death, or loss to follow-up
Treatment of acute hepatitis C: recommendations from an expert panel of the Italian Society of Infectious and Tropical Diseases
Aim: This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC). Methods: This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations. Results: Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments. Conclusions: Early treatment with DAA should be offered when available
Safety of darunavir/ritonavir (DRV/r) in HIV-1-infected DRV/r-experienced and -naïve patients: analysis of data in the real-world setting in Italy
Introduction: This descriptive, non-interventional study on HIV-1-infected patients treated with DRV/r in the usual clinical setting, with a single-arm prospective observational design, collected data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in marketing authorization in usual clinical practice in Italy to evaluate efficacy and safety of DRV/r-based antiretroviral (ARV) treatment. This analysis focussed on the safety profile of DRV/r in HIV-1 infected patients. Materials and Methods: Data were analyzed from four cohorts of HIV-1-infected patients treated with DRV/r in the real-world setting, including an ARV-naïve-DRV/r-naïve cohort (Cohort 1), an ARV-experienced-DRV/r-naïve cohort (Cohort 2) and two ARV-DRV/r-experienced cohorts (Cohorts 3 and 4), one of which (Cohort 3) was from the DRV/r Early Access Program. The objective of this analysis was to examine the safety data obtained in these four cohorts in patients enrolled from June 2009 to November 2011 and observed until December 2012 or DRV/r discontinuation. Results: Safety data from 875 patients were analyzed. DRV/r-based treatment was well tolerated, with 36.2% of patients reporting ≥1 adverse event (AE) and very few discontinuations due to study drug-related AEs (3.0% overall). The most frequent AEs were diarrhoea (2.7%), reduced bone density (2.6%) and hypercholesterolaemia (2.1%) (Table 1). Regarding metabolic parameters, levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) remained stable from baseline to the last study visit (LSV) in DRV-experienced patients and decreased in DRV-naïve patients. Blood glucose concentrations remained stable in all cohorts. Serum triglyceride and cholesterol concentrations remained stable in DRV-experienced patients but increased in naïve patients, yet were still within normal range. Conclusions: In HIV-1-infected patients treated with DRV/r in these settings, the tolerability profile was favourable and similar to (or better than) that reported in controlled clinical trials. These data confirm DRV/r to be a safe treatment choice in DRV/r-experienced and naïve patients
Treatment of acute hepatitis C: recommendations from an expert panel of the Italian Society of Infectious and Tropical Diseases
Aim: This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC). Methods: This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations. Results: Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments. Conclusions: Early treatment with DAA should be offered when available
Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma
Purpose: Accumulating evidences show a higher incidence of hepatic neoplasm in HIV/hepatitis C virus (HCV) - coinfected individuals compared with HCV-monoinfected patients. Treatment with HIV-1 protease inhibitors inhibited cancer-promoted angiogenesis in HIV-infected patients affected by Kaposi sarcoma. We aimed to evaluate the antineoplastic potential activities of the protease inhibitor indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models. Experimental Design: We analyzed effects of indinavir on cell growth and invasiveness in Huh7 and SK-HEP-1 hepatocarcinoma cell lines and on in vivo tumor growth of the same cells in nude mice. Morphologic and molecular analyses on explanted tumors were carried out to evaluate vascularization and apoptosis. Results: We observed a reduced ability to invade an in vitro extracellular matrix for both cell lines treated with indinavir compared with controls (P = 0,001). Moreover, indinavir treatment was able to inhibit matrix metalloproteinase-2 proteolytic activation, whereas there was no effect on cell proliferation. The drug was also able to delay in vivo tumor growth. The inhibition of tumor growth was statistically significant from days 6 to 21 (P = 0.004 and P = 0.003, respectively). Moreover, the drug showed antiangiogenic and proapoptotic actions, as revealed by vessel count and apoptotic index by terminal deoxynucleotide transferase - mediated nick end labeling in explanted tumors. Finally, treatment with indinavir did not block the production of vascular endothelial growth factor in the tumors. Conclusion: Indinavir could be helpful to prevent the development of hepatocarcinomas in HIV/HCV - coinfected individuals. In view of the current trend to substitute protease inhibitors with other antiretroviral agents, this information may have clinical implications. © 2006 American Association for Cancer Research