Search results for " protease inhibitors"
showing 10 items of 28 documents
Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease in…
2011
Abstract Background Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce. Methods Subjects with virological success on first-PI-regimens who switched to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after…
Twenty Years of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Time to Reevaluate their Toxicity
2011
Twenty years of effective clinical application have consolidated non-nucleoside reverse transcriptase inhibitors (NNRTI) as essential components of the Highly Active Antiretroviral Therapy (HAART) employed in the treatment of Human Immunodeficiency Virus (HIV). However, as the disease has come under control, there has been growing emphasis on the long-term adverse effects induced by this chronic pharmacological therapy. Although traditionally considered to be safe and well-tolerated drugs, there is mounting evidence that associates NNRTI with the onset of cutaneous reactions, neuropsychiatric symptoms, hepatotoxicity, metabolic disturbances and gastrointestinal toxicity. Though the clinical…
Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cry…
2003
With the spread of the human immunodeficiency virus in the early 1980s, cryptosporidiosis was regarded as an AIDS-defining disease. As an opportunistic pathogen, the intestinal parasite Cryptosporidium parvum became an important cause of chronic diarrhoea, leading to high morbidity and mortality in immunocompromised patients. To date, no effective chemotherapy is available. With the introduction of protease inhibitors (PIs) in highly active antiretroviral therapy (HAART), the incidence of cryptosporidiosis in AIDS patients has declined substantially in western countries. We have therefore tested the effect of five PIs used in HAART on the excystation, invasion and development of the parasit…
Reversible posterior leukoencephalopathy secondary to indinavir-induced hypertensive crisis: A case report
2002
Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon entity related to multiple and different pathologies, the most common being hypertensive crisis. It is believed to be secondary to the breakdown on the blood-brain barrier. At the beginning, it is undistinguishable from other leukoencephalopathies. However, the disappearance of brain lesions after removal of the potential cause, establish the differential diagnosis with other leukoencephalopathies. We present the case of an HIV-infected patient with a RPLS related to a hypertensive crisis short after the initiation of indinavir-containing highly active antiretroviral therapy. Once blood pressure was controlled and indin…
Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort
2019
AbstractObjectivesTo evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017.Patients and methodsIn total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases…
Molecular Classification of N-Aryloxazolidinone-5-carboxamides as Human Immunodeficiency Virus Protease Inhibitors
2015
Algorithms for classification and taxonomy are proposed in this chapter based information entropy (IE) and its production. The 38 N- aryloxazolidinone-5-carboxamides (NCAs), for human immunodeficiency virus (HIV) protease (PR) inhibition, are classified using seven characteristic chemical properties of different moieties: R 1/2 , R 3–6 on different phenyls and R 7 . Many classification algorithms are based on IE. When applying some procedures to moderate-sized sets, excessive number of results appear compatible with the data and suffer combinatorial explosion. However, after the equipartition conjecture (EC), one has a selection criterion among different variants that results from classifi…
Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver …
2015
In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (…
Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe
2016
Transmitted human immunodeficiency virus drug resistance in Europe is stable at around 8%. The impact of baseline mutation patterns on susceptibility to antiretroviral drugs should be addressed using clinical guidelines. The impact on baseline susceptibility is largest for nonnucleoside reverse transcriptase inhibitors.
Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis.
2012
Introduction: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. Results: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the ma…
Docking and multivariate methods to explore HIV-1 drug-resistance: a comparative analysis
2007
In this paper we describe a comparative analysis between multivariate and docking methods in the study of the drug resistance to the reverse transcriptase and the protease inhibitors. In our early papers we developed a simple but efficient method to evaluate the features of compounds that are less likely to trigger resistance or are effective against mutant HIV strains, using the multivariate statistical procedures PCA and DA. In the attempt to create a more solid background for the prediction of susceptibility or resistance, we carried out a comparative analysis between our previous multivariate approach and molecular docking study. The intent of this paper is not only to find further supp…