Collaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretation

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dc.contributor.authorParedes, Rogeren_ZA
dc.contributor.authorTzou, Philip L.en_ZA
dc.contributor.authorVan Zyl, Gerten_ZA
dc.contributor.authorBarrow, Geoffen_ZA
dc.contributor.authorCamacho, Ricardoen_ZA
dc.contributor.authorCarmona, Sergioen_ZA
dc.contributor.authorGrant, Philip M.en_ZA
dc.contributor.authorGupta, Ravindra K.en_ZA
dc.contributor.authorHamers, Raph L.en_ZA
dc.contributor.authorHarrigan, P. Richarden_ZA
dc.contributor.authorJordan, Michael R.en_ZA
dc.contributor.authorKantor, Ramien_ZA
dc.contributor.authorKatzenstein, David A.en_ZA
dc.contributor.authorKuritzkes, Daniel R.en_ZA
dc.contributor.authorMaldarelli, Franken_ZA
dc.contributor.authorOtelea, Danen_ZA
dc.contributor.authorWallis, Carole L.en_ZA
dc.contributor.authorSchapiro, Jonathan M.en_ZA
dc.contributor.authorShafer, Robert W.en_ZA
dc.date.accessioned2018-11-13T09:36:13Z
dc.date.available2018-11-13T09:36:13Z
dc.date.issued2017-07-28
dc.descriptionCITATION: Paredes, R., et al. 2018. Collaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretation. PLoS ONE, 12(7):e0181357, doi:10.1371/journal.pone.0181357.
dc.descriptionThe original publication is available at https://journals.plos.org/plosone
dc.description.abstractIntroduction: HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve. Methods: An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations. The DRM pattern-ARV combinations included 52 nucleoside RT inhibitor (NRTI) DRM pattern-ARV combinations (13 patterns x 4 NRTIs), 27 nonnucleoside RT inhibitor (NNRTI) DRM pattern-ARV combinations (9 patterns x 3 NNRTIs), 39 protease inhibitor (PI) DRM pattern-ARV combinations (13 patterns x 3 PIs) and 42 integrase strand transfer inhibitor (INSTI) DRM pattern-ARV combinations (14 patterns x 3 INSTIs). Results: There was universal agreement that a GRT report should include the NRTIs lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir disoproxil fumarate; the NNRTIs efavirenz, etravirine, nevirapine, and rilpivirine; the PIs atazanavir/r, darunavir/r, and lopinavir/r (with “/r” indicating pharmacological boosting with ritonavir or cobicistat); and the INSTIs dolutegravir, elvitegravir, and raltegravir. There was a range of opinion as to whether the NRTIs stavudine and didanosine and the PIs nelfinavir, indinavir/r, saquinavir/r, fosamprenavir/r, and tipranavir/r should be included. The expert panel members provided highly concordant DRM pattern-ARV interpretations with only 6% of NRTI, 6% of NNRTI, 5% of PI, and 3% of INSTI individual expert interpretations differing from the expert panel median by more than one resistance level. The expert panel median differed from the HIVDB 7.0 GRT-IS for 20 (12.5%) of the 160 DRM pattern-ARV combinations including 12 NRTI, two NNRTI, and six INSTI pattern-ARV combinations. Eighteen of these differences were updated in HIVDB 8.1 GRT-IS to reflect the expert panel median. Additionally, HIVDB users are now provided with the option to exclude those ARVs not considered to be universally required. Conclusions: The HIVDB GRT-IS was updated through a collaborative process to reflect changes in HIV drug resistance knowledge, treatment guidelines, and expert opinion. Such a process broadens consensus among experts and identifies areas requiring further study.en_ZA
dc.description.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181357
dc.description.versionPublisher's version
dc.format.extent31 pagesen_ZA
dc.identifier.citationParedes, R., et al. 2018. Collaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretation. PLoS ONE, 12(7):e0181357, doi:10.1371/journal.pone.0181357
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0181357
dc.identifier.urihttp://hdl.handle.net/10019.1/104679
dc.language.isoen_ZAen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectHIV antibodiesen_ZA
dc.subjectDrug resistanceen_ZA
dc.subjectPharmacogenomicsen_ZA
dc.subjectGenomes -- Effect of drugs onen_ZA
dc.titleCollaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretationen_ZA
dc.typeArticleen_ZA
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