Scandinavian journal of infectious diseases. Supplementum最新文献

{"title":"Supreme Court decision on genotypic tests for antiretroviral drugs resistance: Joint Criminal Divisions.","authors":"F Dianzani, E Frascione","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"108-9"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic resistance tests for the management of structured therapeutic interruptions after multiple drug failure.","authors":"Maria Montroni,&nbsp;Antonella D'Arminio Monforte","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Witness for the prosecution: Structured treatment interruption (STI) has been considered among the possible therapeutic options for multidrug experienced HIV-infected individuals facing virological failure, since early studies suggested the possibility of viral reversion from drug-resistant mutated species to drug-sensitive wild-type virus following the release of drug pressure. However, the persistence of mutated viral populations during STI has been observed. The lack of detection of resistance mutations in plasma is mainly due to the low sensitivity of the currently available genotypic resistance testing, which is unable to detect resistant less fit virus masked by overwhelming re-emerged wild-type quasi-species. Restarting antiretroviral therapy (ART) is frequently followed by the reappearance of resistant virus, as well as by disease progression. STI should be applied with extreme caution in multidrug experienced HIV-infected individuals with virological failure. Use of genotype resistance testing in this particular setting, although useful in controlled clinical trials, should be considered of little help in clinical practice. Witness for the defence: The rationale for salvage STI has been elucidated. Data from observational and randomized studies have been revised, and the following conclusions in defence of salvage STI are: in more than 60% of patients undergoing salvage STI for at least 3 months there is a reversion of drug-associated mutations. Concurrently, increases in HIV-RNA and decreases in CD4 cells occur. Few clinical events have been reported in patients with CD4 counts of < 200 cells/mm3. New resistance-driven salvage regimens, including at least 1 new drug, result in good virological outcome in a short-term follow-up. Warnings are related to possible clinical progression and to the course of the infection in reservoirs. Randomized studies are required to elucidate these findings.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"79-81"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24426018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral resistance to chemotherapeutic agents: an expectable unexpected phenomenon.","authors":"Ferdinando Dianzani","doi":"10.1080/03008870310016238","DOIUrl":"https://doi.org/10.1080/03008870310016238","url":null,"abstract":"","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"6-7"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310016238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24424957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic resistance tests for the clinical management of patients with primary HIV infection.","authors":"Pasquale Narciso,&nbsp;Adriano Lazzarin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Witness for the prosecution: Assays to detect antiretroviral drug resistance have recently become available, but several factors limit the clinical utility of resistance testing in patients with primary HIV infection (PHI). First, there is a great uncertainty in the prevalence of PHI due to resistant virus, which may vary from 2% to over 50%. Moreover, studies on temporal trends give discordant results. Secondly, the reported degree of resistance is also variable since low levels of resistance are reported in some cases. The clinical significance of such low-level baseline reduced susceptibility to some antiretrovirals is uncertain. Thirdly, current resistance testing might not detect minority populations of drug-resistant species. Reversion of mutations conferring drug resistance was described in patients who acquired drug-resistant strains, and viral strains harbouring drug-resistant mutations may become minor species in untreated patients owing to the absence of drug pressure. Finally, no prospective clinical trials have been conducted to test the clinical or virological utility of resistance testing in PHI. Witness for the defence: A suboptimal initial regimen in subjects infected with drug-resistant virus may be associated with multiple treatment failures in the early stage of the disease and hence with a more rapid disease progression. When treating PHI, immediate, complete and long-lasting suppression of virus replication is desired both to limit total body viral burden and to preserve HIV-1 specific immune responses. Transmission of resistant virus has been identified for each therapeutic class. A greater than 2.5-fold resistance to one or more antiretroviral agent has been observed in 26% of patients with PHI and resistance among newly infected patients has increased over the past 3 y. Treatment should not be delayed to wait for the result of the test. However, once a resistant virus has been identified, one or more drugs can be readily substituted. Prospective randomized studies to address the need for baseline resistance testing in the setting of PHI are warranted.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"66-70"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular issues relating to the resistance of HIV to antiretroviral agents.","authors":"Ombretta Turriziani,&nbsp;Carolina Scagnolari,&nbsp;Francesca Bellomi,&nbsp;Isabella Solimeo,&nbsp;Federico Focher,&nbsp;Guido Antonelli","doi":"10.1080/03008870310009669","DOIUrl":"https://doi.org/10.1080/03008870310009669","url":null,"abstract":"<p><p>It has been proposed that the declining efficiency of antiretroviral agents in human immunodeficiency virus (HIV) infection may also depend on cellular factors at their site of action. Two in particular have been proposed: (i) the defective intracellular metabolism of NRTI in target cells and the altered uptake; and (ii) efflux of nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) by cellular transporter molecules. Several studies have shown that: changes in the activities of various purine and pyrimidine biosynthetic enzymes may occur in lymphocytes of HIV-infected patients; HIV-infected patients on prolonged treatment with nucleoside analogues, e.g. zidovudine, show significantly decreased activity of thymidine kinase (TK) compared with untreated HIV-infected people; and NRTI and PI are substrates for the multidrug membrane transporters. With regard to the latter issue, it is known that the ATP-binding cassette transporter proteins such as the P-glycoprotein (MDR), and the newly discovered family of multidrug resistance-associated proteins (MRP1-6), promote the active extracellular efflux of a wide variety of therapeutics drugs and overexpression of some of them lowers intracellular concentration of PI. In the very near future such mechanisms, also called 'cellular drug resistance', might be taken into account, together with other immunological, virological and behavioural factors, to explain the 'drug failure' and/or the variability of response in HIV patients undergoing antiretroviral treatment.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"45-8"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009669","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretation systems for genotypic drug resistance of HIV-1.","authors":"Andrea De Luca,&nbsp;Andrea Antinori,&nbsp;Simona Di Giambenedetto,&nbsp;Antonella Cingolani,&nbsp;Manuela Colafigli,&nbsp;Carlo Federico Perno,&nbsp;Roberto Cauda","doi":"10.1080/03008870310009623","DOIUrl":"https://doi.org/10.1080/03008870310009623","url":null,"abstract":"<p><p>Genotypic assays are widely used tools for determining human immunodeficiency virus type 1 (HIV-1) drug resistance and for guiding treatment changes in patients failing antiretroviral therapy. Several systems have been developed to interpret the complex influence of key amino acid substitutions of the enzymes targeted by therapy on the phenotypic susceptibility or clinical response to available antiretroviral agents. This overview identifies 21 systems giving an interpretation on how amino acid substitutions affect phenotypic drug susceptibility or clinical activity of anti-HIV-1 agents. There was substantial variability in the mechanisms underlying the interpretations, the nature of the systems, their intended use, the source type of their knowledge base, and their update and output. Most of the systems could be accessed for free on the internet, functioned as rule-based algorithms updated by experts and at least partially based on literature evidence, and offered an automated report through a software. Nevertheless, the rule base was not always clarified. An update of the rules and the clinical validation of the systems are presented to help in the critical evaluation of their possible use. Importantly, only 8 systems were intended for clinical use and 5 of these had at least partially undergone clinical validation.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"29-34"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009623","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24424963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief summary of the legal proceeding.","authors":"Emanuele Nicastri","doi":"10.1080/03008870310009849","DOIUrl":"https://doi.org/10.1080/03008870310009849","url":null,"abstract":"<p><p>The panel, held in Rome in April 2002 with the participation of more than 100 Italian directors of infectious diseases wards, followed a systematic approach to reviewing the evidence of any specific use of the genotypic assays to detect antiretroviral resistance. The single recommendations have been developed using a rating scheme based on consideration of the evidence and, when direct evidence was lacking, on expert opinion. Another emerging issue approached during this meeting is represented by the reproducibility of HIV-1 reverse transcriptase and protease sequencing in clinical settings. The degree of concordance of genotypic assays among 12 experienced laboratories is also reported.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"105-7"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV fitness and resistance as covariates associated with the appearance of mutations under antiretroviral treatment.","authors":"Carlo Federico Perno,&nbsp;Alessandra Cenci,&nbsp;Cristina Piro,&nbsp;Roberta D'Arrigo,&nbsp;Luisa Marcon,&nbsp;Francesca Ceccherini-Silberstein,&nbsp;Franca Ascoli Marchetti,&nbsp;Raffaele Caliò,&nbsp;Andrea Antinori","doi":"10.1080/03008870310009641","DOIUrl":"https://doi.org/10.1080/03008870310009641","url":null,"abstract":"<p><p>The ability of human immunodeficiency virus (HIV) strains to replicate in human target cells represents a major driving force of the progression of the disease. Despite antiretroviral treatment, HIV overcomes drug pressure by adding new (compensatory) mutations, appearing in a specific and sequential order, that modulate its replication capacity and favour viral escape. In the case of M184V (a mutation involving the catalytic site of HIV reverse transcriptase), no pathways of viral escape have been defined so far; it is thus conceivable that the mutated virus maintains a relatively low replicative capacity. At the time of interruption of specific viral pressure (lamivudine in the case of M184V), wild-type virus easily overgrows mutated strains. A deep molecular analysis (90 clones) conducted on proviral DNA of lymphocytes demonstrates that M184V strains are no longer detected in plasma and proviral DNA shortly after interruption of therapeutic regimens including lamivudine (even if a new therapeutic regimen has been started). This supports the concept that the low fitness of M184V strains is not easily compensated by additional mutations. Taken together, the results suggest that the assessment of viral fitness, either direct (through biological methods) or indirect (through the identification of specific mutations that affect the replicative capacity), may provide substantial advancements in the definition of the long-term efficacy of antiretroviral therapy.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"37-40"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness analysis of using antiretroviral drug resistance testing.","authors":"Francesco Nicola Lauria,&nbsp;Claudio Angeletti","doi":"10.1080/03008870310009687","DOIUrl":"https://doi.org/10.1080/03008870310009687","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV)-infected patients failing highly active antiretroviral therapy (HAART) have a substantially lower chance of clinical success than naive patients given their first antiretroviral therapy. This suggests that HAART failure is a determinant for an increase in the cost of treatment. A review of the literature regarding cost and impact of antiretroviral drug-resistance testing was performed. Examination of existing methods to execute a cost-effectiveness analysis on the use of these tests in clinical practice was also undertaken. The cost of treatment failure in HIV-infected patients has been quantified in several retrospective studies. The cost of care for patients with virological suppression was significantly lower than those with a single virological failure. Moreover, the latter group had lower costs than patients with multiple failures. The result of the cost-effective analysis based on a specific model application using genotypic resistance assays to guide the choice of a subsequent therapy in HIV disease, is cost-effective under a wide range of assumptions regarding effectiveness and costs. The available studies on the cost-effective evaluation of genotypic tests are limited, and the respective studies supply important indications on cost-effective evaluations. Despite its demonstrated benefits, antiretroviral drug resistance testing presents features and limitations that also restrict the cost-effectiveness analysis.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"54-7"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009687","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The legal proceeding: introduction of the witnesses.","authors":"Emanuele Nicastri","doi":"10.1080/03008870310009731","DOIUrl":"https://doi.org/10.1080/03008870310009731","url":null,"abstract":"For the purposes of this proceeding, either the witness for defence or the plaintiff will discuss the strength and the level of each single indication for the use of genotypic assays for the detection of antiretroviral resistance. The witnesses will consider the peer-reviewed medical literature and the experts’ opinions expressed during international scientific congresses to promote or not to promote the use of genotypic assays.","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"58-60"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}