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European Recommendations for the Clinical Use of HIV Drug Resistance Testing: 2011 Update

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European Recommendations for the Clinical Use of HIV Drug Resistance Testing: 2011 Update AIDS Rev. 2011;13:77-108 Anne-Mieke Vandamme, et al.: European HIV Drug Resistance Guidelines European Recommendations for the Clinical Use of HIV Drug Resistance Testing: 2011 Update Anne-Mieke Vandamme1,2, Ricardo J. Camacho2,3, Francesca Ceccherini-Silberstein4, Andrea de Luca5, Lucia Palmisano6, Dimitrios Paraskevis7, Roger Paredes8, Mario Poljak9, Jean-Claude Schmit10, Vincent Soriano11, Hauke Walter12, Anders Sönnerborg13 and the European HIV Drug Resistance Guidelines Panel 1Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium; 2Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal; 3Laboratório de Biologia Molecular, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal; 4Department 5 of Experimental Medicine,University of Rome Tor Vergata, Rome, Italy; Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro © Permanyer Publications 2011 Cuore, Roma, and Second Division of Infectious Diseases, Siena University Hospital, Siena, Italy; 6Istituto Superiore di Sanità, Rome, Italy; 7National Retrovirus Reference Center, Department of Hygiene Epidemiology and Medical Statistics, Medical School University of Athens, Athens, Greece; 8 HIV Unit & IrsiCaixa AIDS Research Institute, Hospital Universitàri Germans Trias i Pujol, Badalona, Spain; 9Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; 10National Service of Infectious Diseases, Retrovirology Laboratory Luxembourg, Centre Hospitalier de Luxembourg, Luxembourg; 11Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain; 12Institute of Clinical and Molecular Virology, German National Reference Centre for Retroviruses, Erlangen, Germany; 13Divisions of Infectious Diseases and Clinical Virology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. of the publisher Abstract The European HIV Drug Resistance Guidelines Panel, established to make recommendations to clinicians and virologists, felt that sufficient new information has become available to warrant an update of its recommendations, explained in both pocket guidelines and this full paper. The Panel makes the following recommendations concerning the indications for resistance testing: for HIV-1 (i) test earliest sample for protease and reverse transcriptase drug resistance in drug-naive patients with acute or chronic infection; (ii) test protease and reverse transcriptase drug resistance at virologic failure, and other drug targets (integrase and envelope) if such drugs were part of the failing regimen; (iii) consider testing for CCR5 tropism at virologic failure or when a change of therapy has to be made in absence of detectable viral load, and in the latter case test DNA or last detectable plasma RNA; (iv) consider testing earliest detectable plasma RNA when a successful nonnucleoside reverse transcriptase inhibitor-containing therapy was inappropriately interrupted; (v) genotype source patient when postexposure prophylaxis is considered; for HIV-2, (vi) consider resistance testing where treatment change is needed after treatment failure. The Panel recommends genotyping in most situations, using updated and clinically evaluated interpretation systems. It is mandatory that laboratories performing HIV resistance tests take part regularly in external quality assurance programs, and that they consider storing samples in situations where resistance testing cannot be performed as recommended. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response. (AIDS Rev. 2011;13:77-108) Corresponding author: Anne-Mieke Vandamme, [email protected] Key words HIV. Antiviral therapy. Drug resistance testing. Guidelines. Genotype. Phenotype. Correspondence to: Anne-Mieke Vandamme Rega Institute for Medical Research, K.U. Leuven Minderbroedersstraat 10 B-3000 Leuven, Belgium E-mail: [email protected] No part of this publication may be reproduced or photocopying without the prior written permission 77 AIDS Reviews. 2011;13 the specific European situation as discussed in this ntroduction I document. They pertain mainly to geographical differ- ences in transmission of resistant virus, differences in In 2004, the European HIV Drug Resistance Guide- prevalence of HIV-1 subtypes and HIV-2, to the imple- lines Panel presented recommendations for the use mentation of resistance testing throughout Europe, of HIV-1 drug resistance testing for treatment man- which is often related to cost issues, and to differ- agement, with special attention to the European set- ences in education strategies. ting and to quality control measures in the laboratory1,2. This paper contains scientific support for the deci- As sufficient new information has now become avail- sions of the Panel (See: General concepts of HIV able, especially regarding the new drug classes target- antiviral drug resistance and specific points of inter- ing HIV integrase and entry, the Panel worked on an est), recommendations addressed to the clinician © Permanyer Publications 2011 update in the form of pocket guidelines3, which were designing the best possible long-term therapy strategy presented to the public during the 7th European HIV for an individual patient (See: Clinical indications for Drug Resistance Workshop, 25-27 March, 2009, in drug resistance testing), recommendations addressed Stockholm, Sweden, and further updated in this full to laboratories regarding resistance testing and proper paper. The current Panel consists of the members of reporting to the clinician (See: Genotyping or pheno- the original Panel who actively participated in the dis- typing; Interpretation systems), and a proposal for of the publisher cussion of the updated guidelines, with the addition of quality control measures and cost-effectiveness con- new members who were recruited to maintain a bal- siderations to the authorities (See: Laboratory quality anced expertise. The current Panel received unrestrict- control requirements for sequencing; Sample storage; ed educational grants from several pharmaceutical Cost issues). The recommendations summarized in and diagnostic companies to cover the logistic costs, table 1 are graded to indicate strength of recommen- such as meeting rooms and print costs. None of the dation and level of evidence, and contain in addition Panel members received fees or travel reimbursement the level of consensus among the Panel. The updates for their work. to previous guidelines are mentioned throughout the The current European HIV Drug Resistance Guide- document and consist mainly of scientific data on lines Panel consists of experts from mainly European transmitted drug resistance, updated evidence and countries, 20 academic clinicians and 20 academic recommendations with regard to resistance to the new virologists from 22 European countries, 12 experts in drug classes integrase inhibitors and coreceptor an- the field from pharmaceutical or diagnostic companies, tagonists, technical improvements, and cost issues. one statistician/epidemiologist as well as one represen- tative of an European patient organization. Discussions General concepts of HIV antiviral drug were undertaken during four on-line and one face-to- resistance and specific points of interest face discussion meetings, from January, 2009 to No- vember, 2010. Further e-mail communication was Understanding antiretroviral extensive to arrive at the final pocket guidelines and drug resistance the current full paper. The recommendations as men- tioned in this document were voted on by the Panel, Resistance reduces therapeutic options with the total number of completed votes being 38. Panel members employed by a commercial company Current therapeutic choices for the treatment of HIV involved in resistance testing or drug development had infections have considerably expanded over time but no voting power to avoid conflict of interest situations, remain limited. While 23 different anti-HIV drugs from but their expertise contributed significantly to the dis- five classes are currently available to the patient, these cussions and the resulting documents. For some coun- are used in a limited number of combinations of usually tries, clinicians and/or virologists chose to consult their three or more drugs6,7. Development of drug resistance colleagues (also mentioned in the Panel), without in- is both the cause and consequence of a failing antiret- creasing the number of votes for that country. The roviral therapy (ART)8. How fast and which mutations level of consensus in table 1 reflects the result of this arise depends on the interplay between several fac- voting. The final document was approved by all Panel tors such as drug potency, genetic barrier, patient members. The European guidelines differ from the adherence to treatment, host genetics, and the contri- No part of this publication may be reproduced or photocopying without the prior written permission international and US guidelines4,5 on issues related to bution of specific mutations to virus drug resistance 78 Anne-Mieke Vandamme, et al.: European HIV Drug Resistance Guidelines Table 1. Recommendations for drug resistance testing in the European setting Clinical Recommendation to clinicians Recommendation indication and evidence level Academic consensus
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