Scandinavian journal of infectious diseases. Supplementum最新文献

{"title":"Use of genotypic assays for the detection of antiretroviral resistance: a legal proceeding, Rome, 22-23 April 2002.","authors":"Anders Sönnerborg","doi":"10.1080/03008870310009876","DOIUrl":"https://doi.org/10.1080/03008870310009876","url":null,"abstract":"Dramatic decreases in morbidity and mortality have been seen among HIV-infected patients since the introduction of potent antiretroviral therapy. However, the overuse of antiretroviral therapy in many clinics has contributed to a high treatment failure rate with a concomitant development of resistance to the drugs. Thus, resistance issues, together with problems related to long-term side effects, have emerged as the major threats to the long-term outcome of antiretroviral therapy. As for most anti-HIV drugs, resistance testing has been introduced into the clinic at an early stage of clinical development, before solid proof has been presented in the favour of their use. Theoretical considerations and a few clinical studies have given support to the clinicians who have used these assays. However, many of the scientific data have been presented by scientists working for or in close collaboration with commercial companies promoting the resistance assays. Therefore, it is of great value for the scientific community and for clinicians within the HIV field to have the opportunity to read a thorough analysis of the scientific evidence presented at the ‘Trial on tests for resistance to antiretroviral drugs’, held in Rome in April 2002.","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24424956","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 the HIV-infected pregnant woman.","authors":"Dante Bassetti,&nbsp;Antonietta Cargnel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Witness for the prosecution: Recommendations for genotypic resistance testing in HIV-infected pregnant women are the same as for non-pregnant women: acute HIV infection, virological failure or suboptimal viral suppression after initiation of antiretroviral therapy, or high likelihood of exposure to resistant virus based on community prevalence or source characteristics. All pregnant women with detectable HIV-RNA levels should perform resistance testing to maximize the response to antiretrovirals in pregnancy. Currently there are no data on the value of drug resistance testing to prevent vertical transmission. Most studies show that the most important factor in the risk of transmission is the amount of HIV-RNA at the moment of delivery. A strategy to overcome this problem would be to use of resistance testing to select a regimen, which has the greatest potential to reduce viral load at the moment of delivery. We would also like to use the same information to select the regimen that would be used to provide prophylaxis to the newborn. It is currently unknown whether zidovudine (ZDV) prevents transmission through another mechanism(s) in addition to reducing viral load, so one could argue that even if ZDV resistance has been found in the mother, it should still be included in the regimen. Witness for the defence: To reduce the risk of HIV vertical transmission, prospective controlled trials on the use of antiretroviral prophylactic treatment in different schedules during pregnancy were conducted. These studies assessed the efficacy of short- or medium-term antiretroviral therapy in reducing vertical transmission, but highlighted the concerns about the selection of resistant variants (monotherapy prophylaxis or suboptimal regimens). The availability of recent more complex multidrug regimens increased the prevalence of drug resistance among the HIV-1-infected population; so, women of childbearing age are at risk of becoming infected with resistant virus and those on treatment, living in developed countries, could harbour resistant virus before pregnancy. Therefore, there are growing concern about the role of these resistant variants in mother-to-child HIV-1 transmission. Several studies documenting HIV-resistant variants in vertical transmission form a compelling basis for recommending the use of HIV-1 genotypic drug resistance tests during pregnancy. Owing to the availability of different genotypic HIV-1 tests at variable costs, the choice of the most appropriate assay could take into account the prevalence and incidence of drug-resistant mutations, the availability of drugs and the antiretroviral experience setting, to choose the best long-term effective antiretroviral therapy for the mother and to avoid the risk of transmission to the offspring.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"70-4"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24426016","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 the patient failing highly active antiretroviral therapy: the resistance pattern in different biological compartments.","authors":"Giuseppina Liuzzi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Single witness: HIV-1 drug resistance assays have been shown to be of value for guiding antiretroviral therapy (ART) decisions. Different tissues or body fluids in which HIV-1 can reside may contain viruses with distinct characteristics. HIV-1 variants with genotypic resistance markers are present in the male genital tract and evolve over time on incompletely suppressive ART. The magnitude of decline in the semen HIV-RNA level in with therapy is usually similar to the effect of treatment on the blood viral burden. Not all men on ART have complete suppression of HIV-1 replication in genital tract; thus, they may shed resistant HIV-1 strains. Failure of treatment to suppress HIV-RNA levels in the blood is common, resulting in the selection of resistant HIV-1 variants. Sexual transmission of resistant variants may have a negative impact on treatment outcome in newly infected individuals and on the spread of the diseases within a population. The use of rapid assessment of HIV resistance in plasma and semen may be useful in some situations, e.g. HIV transmitted infection by sexual contact from a viraemic patient. The recognition of resistant HIV isolates in the blood and semen of patients receiving ART leads to the question of the potential role of resistance testing. In many but not all infectious diseases, the choice of therapy is guided by sensitivity testing. Recent data suggest that testing the drug sensitivity of viral isolates from the blood can benefit patient management and response to therapy, albeit at considerable cost. However, since drug resistance may evolve independently in blood and semen, the public health benefits of such testing are unproven.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"90-3"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24426022","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 postexposure prophylaxis.","authors":"Vincenzo Puro","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Single witness: Given the increased utilization of highly active antiretroviral therapy (HAART) and the growing number of patients harbouring a drug-resistant virus, the potential exists to become infected with drug-resistant HIV. Available data suggest the emergence of drug-resistant HIV among source persons for occupational exposures. Despite this non-negligible rate, none of the health-care workers have become infected with HIV. The prevalence of antiretroviral resistance is high among source patients who reported any use of antiretroviral agents and is rare among those who reported no history of use, and in the majority of cases of failure of postexposure prophylaxis (PEP), the source was reported to have experience of the same agents included in the PEP regimen provided to the exposed individual. There are no data available to demonstrate that resistance testing leads to improvements in PEP outcomes. In fact, testing HIV isolates from a source patient, when available, for antiretroviral resistance would be of no immediate significance, as PEP should be initiated within hours of the exposure. The source patient's treatment history may be helpful in predicting which resistance mutations might be present in the source isolate.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"93-8"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24426023","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":"Global HIV drug resistance surveillance.","authors":"Annapaola De Felici","doi":"10.1080/03008870310009605","DOIUrl":"https://doi.org/10.1080/03008870310009605","url":null,"abstract":"<p><p>The transmission of drug-resistant strains of human immunodeficiency virus (HIV) is of increasing concern in countries where antiretroviral therapy is widely used and does not spare countries where highly effective antiretroviral therapy has been recently introduced. The global HIV drug resistance surveillance programme will track the drug susceptibility in a rapidly moving epidemic, to provide information necessary to develop effective treatment strategies, to support and complement programmes aimed at increasing HIV therapy availability, and to assist in targeting and complementing drug resistance prevention strategies.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"21-3"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24424961","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":"Virological efficacy in HIV-infected patients affected by non-Hodgkin lymphoma, treated with antiblastic chemotherapy and highly active antiretroviral therapy.","authors":"Cecilia Simonelli,&nbsp;Stefania Zanussi,&nbsp;Roberta Cinelli,&nbsp;Luigino Dal Maso,&nbsp;Giampiero Di Gennaro,&nbsp;Monica D'Andrea,&nbsp;Guglielmo Nasti,&nbsp;Michele Spina,&nbsp;Emanuela Vaccher,&nbsp;Paolo De Paoli,&nbsp;Umberto Tirelli","doi":"10.1080/03008870310009678","DOIUrl":"https://doi.org/10.1080/03008870310009678","url":null,"abstract":"<p><p>This study evaluated replication of human immunodeficiency virus (HIV) and the genotypic resistance pattern in 26 HIV-infected patients affected by non-Hodgkin lymphoma who were treated with at least 3 cycles of chemotherapy (CT; rituximab and CDE) and highly active antiretroviral therapy (HAART). Genotyping was performed at baseline and when virological failure occurred. Six patients met the virological failure criteria. The genotyping analysis demonstrated that during CT administration new mutations might occur, but no significant changes in the pre-existing resistance patterns were observed. The data show that a combination therapy consisting of CT and HAART is feasible and that the virological response can be maintained in the majority of such patients.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"49-53"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009678","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425488","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 on the use of genotypic assays for the detection of HIV antiretroviral resistance in Italy: background and rationale for a consensus conference to establish guidelines.","authors":"Giuseppe Ippolito,&nbsp;Ubaldo Visco-Comandini,&nbsp;Emanuele Nicastri","doi":"10.1080/03008870310017110","DOIUrl":"https://doi.org/10.1080/03008870310017110","url":null,"abstract":"<p><p>Do the genotypic assays for the detection of antiretroviral resistance represent a useful tool in the management of HIV-infected patients? The rationale for this legal proceeding is all included in this question. No health care technology assessment has been performed on antiretroviral genotypic assays in HIV-infected patients. Assays to measure drug resistance are available only in specialized laboratories and warnings are related to possible expanded use of these assays in the absence of randomised studies with prolonged clinical endpoint and in the absence of unambiguous and exhaustive general recommendations for the use of resistance assays in clinical practice.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"8-11"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310017110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24424958","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 in the management of the HIV-infected patient at virological failure.","authors":"Antonio Aceti,&nbsp;Giampiero Carosi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Witness for the prosecution: The IAS-USA and Euro-Resistance Group HIV guidelines recommend the use of resistance testing for all patients experiencing treatment failure for whom therapy change is being considered. However, these assays suffer from several limitations (problems in sensitivity, specificity, complexity of interpretation, cost) and the results of the prospective studies evaluating genotype-guided treatment in HIV patients failing antiretroviral treatment are inconclusive and partially contrasting (virological benefit is short-term). On this basis, incorporating genotypic resistance assays into the clinical management of HIV patients experiencing first treatment failure is not a sufficiently evidence-based practice. Witness for the defence: Highly active antiretroviral therapy (HAART) has markedly improved the prognosis of HIV-infected patients by controlling HIV replication. However, HAART fails to control HIV replication in an increasing number of patients as a result of a complex array of causes. There is now substantial evidence that the emergence of drug resistance is a leading cause (as well as consequence) of antiretroviral therapy failure. Moreover, HIV drug resistance can be transmitted and this can favour initial treatment failure. Several retrospective and prospective studies have indicated that both genotypic and phenotypic HIV-1 drug resistance testing results are associated with, or predictive of, the virological outcome. As a consequence, international guidelines have soundly recommended the use of resistance testing to guide treatment choices after virological failure. The rationale and advantages of using such testing after first virological failure will be discussed.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"61-6"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425491","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 the HIV-infected patient with non-B viral isolates.","authors":"Ubaldo Visco-Comandini,&nbsp;Claudia Balotta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Witness for the prosecution: The dominating HIV-1 subtype in Europe and in the USA is the B subtype, but the prevalence of circulating recombinant forms and non-B subtypes (nBS) in Europe has increased. HIV-1 group O strains are spontaneously resistant to non-nucleoside analogue reverse transcriptase inhibitors (NNRTI) and little is known about the antiretroviral (ARV) drug susceptibility of nBS clinical isolates. Controlled randomized trials showing a clinical benefit of a treatment guided by HIV-1 resistance testing at virological failure have been conducted on subtype B. Thus, the result cannot be simply extended to nBS. In nBS, the frequency or amplification failure is increased, but retesting failed samples with an alternative set of polymerase chain reaction primers improves the success of amplification. The major problem is the reliability of genotypic resistance tests (GRT) owing to misinterpretation of the obtained amino acid mutations, the background sequence in nBS being different from the standard used in the commercial kits or in the web-based HIV-1 resistance interpretation tools. At the moment, no nBS database is available to help in the interpretation of the protease and RT sequence results. Furthermore, the mutational pattern of specific ARV drugs may be different, in particular with subtype C and G. In conclusion, in patients with nBS the indication to for at virological failure may exists, even in the absence of clinical evidence, but the results have to be interpreted by experts with particular caution. Witness for the defence: The extensive variability of HIV-1 has a potential impact on epidemiology, diagnosis, therapy and the prevention of infection. Nine different major subtypes of group M (A-D, F-H, J and K) circulate to varying extents in populations around the globe together with the circulating recombinant forms (CRF) owing to intersubtype recombinations. Although viruses belonging to the HIV-1 B clade are still predominant in Europe, the USA and Australia, an increasing prevalence of non-clade B subtypes and CRF has been reported by several surveys in previously homogeneous clade B countries. As current ARV have been designed using subtype B strains and resistance mutations have been characterized on this subtype, the increasing global spread of HIV subtypes highlights the need to determine the activity of anti-HIV drugs against subtypes or CRF other than subtype B.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"75-8"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24426017","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":"Phenotypic resistance testing.","authors":"Massimo Andreoni","doi":"10.1080/03008870310009632","DOIUrl":"https://doi.org/10.1080/03008870310009632","url":null,"abstract":"<p><p>The development of automated assay technology for rapid genotypic and phenotypic characterization of human immunodeficiency virus (HIV) in plasma samples now makes it feasible to use these assays in the management of antiretroviral therapy. In particular, phenotypic assays measure the drug susceptibility of the virus by determining the concentration of drug that inhibits viral replication in tissue culture. Recent experiences suggest that interpreting phenotypes may be more complicated than originally believed. Thus, rather than considering drugs as active or inactive on the basis of cut-offs, it would be more reasonable to consider their relative activity. To complicate matters further, a relatively high incidence of discordance between phenotypic and genotypic results when both tests were performed on plasma samples of antiretroviral treated patients has been reported. These findings could have considerable clinical significance, because the choice of drug regimen could differ depending on which test is used. The result of phenotypic testing may be more important when considering discordant results, because this provides a more quantitative assessment of resistance. However, clinical validation will be necessary to delineate which approach is better.</p>","PeriodicalId":76520,"journal":{"name":"Scandinavian journal of infectious diseases. Supplementum","volume":"106 ","pages":"35-6"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03008870310009632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24425484","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}