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Predicted dolutegravir resistance in people living with HIV in South Africa during 2020-35: a modelling study

dc.rights.licenseopenen_US
dc.contributor.authorLOOSLI, Tom
dc.contributor.authorHAN, Nuri
dc.contributor.authorHAUSER, Anthony
dc.contributor.authorJOSI, Johannes
dc.contributor.authorINGLE, Suzanne M
dc.contributor.authorVAN SIGHEM, Ard
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorWITTKOP, Linda
dc.contributor.authorVEHRESCHILD, Janne
dc.contributor.authorCECCHERINI-SILBERSTEIN, Francesca
dc.contributor.authorMAARTENS, Gary
dc.contributor.authorGILL, M John
dc.contributor.authorSABIN, Caroline A
dc.contributor.authorJOHNSON, Leigh F
dc.contributor.authorLESSELLS, Richard
dc.contributor.authorGUNTHARD, Huldrych F
dc.contributor.authorEGGER, Matthias
dc.contributor.authorKOUYOS, Roger D
dc.date.accessioned2025-05-27T08:19:50Z
dc.date.available2025-05-27T08:19:50Z
dc.date.issued2025-04-01
dc.identifier.issn2214-109Xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/206738
dc.description.abstractEnBACKGROUND: In response to increasing resistance to non-nucleoside reverse transcriptase inhibitors, millions of people living with HIV have switched to dolutegravir-based antiretroviral therapy, so understanding the possible emergence of dolutegravir resistance is essential. We aimed to predict how dolutegravir resistance in South Africa will change over time. METHODS: For this modelling study, we used the Modelling Antiretroviral Drug Resistance in South Africa (MARISA) model, a deterministic compartmental model calibrated to reproduce the HIV-1 epidemic in South Africa from 2005 to 2035 using data from the International Epidemiology Databases to Evaluate AIDS collaboration and the literature. Key parameters for modelling dolutegravir-resistance evolution were acquisition rates of dolutegravir-resistance mutations, reversion rates of dolutegravir-resistance mutations, the effect of resistance to nucleoside reverse transcriptase inhibitors on dolutegravir-resistance acquisition, the effect of dolutegravir resistance on dolutegravir-treatment efficacy, the probability of transmitting dolutegravir drug-resistance mutations compared with the probability of transmitting wild-type HIV, and the proportion of people with virologic failure on dolutegravir-based antiretroviral therapy with detectable drug levels. Model outcomes were estimated transmitted dolutegravir resistance and estimated acquired dolutegravir resistance. FINDINGS: We estimated a substantial increase in the number of individuals on dolutegravir-based antiretroviral therapy after its introduction in 2020, increasing from 0 to approximately 7 million people (7·08-7·15) living with HIV on dolutegravir in 2035. We estimated the proportion of people living with HIV with viral suppression (ie, viral load <1000 copies per mL) on dolutegravir-based antiretroviral therapy to be 93% (uncertainty range 92·2-94·3) in 2035. We estimated that acquired dolutegravir resistance in people living with HIV on failing dolutegravir-based antiretroviral therapy would increase rapidly, from 18·5% (uncertainty range 12·5-25·4) in 2023 to 41·7% (29·0-54·0) in 2035. For transmitted dolutegravir resistance, we estimated an increase from 0·1% (0·0-0·2) in 2023 to 5·0% (1·9-11·9) in 2035. We estimated that resistance-mitigation strategies involving rapid switching to protease-inhibitor-based antiretroviral therapy could effectively reduce the increase in acquired dolutegravir resistance and slow the increase in transmitted dolutegravir resistance. INTERPRETATION: Although dolutegravir-based antiretroviral therapy maintains high virological suppression, acquired and transmitted dolutegravir resistance are likely to increase. This increase will likely be greater in settings where HIV RNA monitoring, genotypic-resistance testing, and options to switch antiretroviral therapy regimens are scarce. FUNDING: US National Institutes of Health National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation, and University of Zurich Research Priority Program Evolution in Action.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enPredicted dolutegravir resistance in people living with HIV in South Africa during 2020-35: a modelling study
dc.title.alternativeLancet Glob Healthen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/s2214-109x(24)00553-9en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed40155107en_US
bordeaux.journalThe Lancet global healthen_US
bordeaux.pagee698-e706en_US
bordeaux.volume13en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue4en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.institutionINRIAen_US
bordeaux.teamSISTM_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDNational Institutes of Healthen_US
bordeaux.identifier.funderIDNational Institute of Allergy and Infectious Diseasesen_US
hal.identifierhal-05086220
hal.version1
hal.date.transferred2025-05-27T08:19:53Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=The%20Lancet%20global%20health&amp;rft.date=2025-04-01&amp;rft.volume=13&amp;rft.issue=4&amp;rft.spage=e698-e706&amp;rft.epage=e698-e706&amp;rft.eissn=2214-109X&amp;rft.issn=2214-109X&amp;rft.au=LOOSLI,%20Tom&amp;HAN,%20Nuri&amp;HAUSER,%20Anthony&amp;JOSI,%20Johannes&amp;INGLE,%20Suzanne%20M&amp;rft.genre=article


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