Show simple item record

dc.contributor.authorRiou, Julien
dc.contributor.authorDupont, Carole
dc.contributor.authorBertagnolio, Silvia
dc.contributor.authorGupta, Ravindra
dc.contributor.authorKouyos, Roger D
dc.contributor.authorEgger, Matthias
dc.contributor.authorL Althaus, Christian
dc.date.accessioned2021-12-24T00:30:43Z
dc.date.available2021-12-24T00:30:43Z
dc.date.issued2021-10-07
dc.identifier.issn1471-2334
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331761
dc.description.abstractINTRODUCTION: The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy's long-term success (ART). NNRTIs will remain an essential drug for the management of HIV-1 due to safety concerns associated with integrase inhibitors. We fitted a dynamic transmission model to historical data from 2000 to 2018 in nine countries of southern Africa to understand the mechanisms that have shaped the HIV-1 epidemic and the rise of pretreatment NNRTI resistance. METHODS: We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on pretreatment NNRTI resistance from nine southern Africa countries from a systematic review, UNAIDS and World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined each national ART programme's vulnerability to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between fragility and characteristics of the health system of each country. RESULTS: The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval 1.9-7.1) in Mozambique and 25.3% (17.9-33.8) in Eswatini. The proportion of pretreatment NNRTI resistance attributable to unregulated antiretroviral use ranged from 6% (2-14) in Eswatini to 64% (26-85) in Mozambique. The fragility index was low in Botswana (0.01; 0.0-0.11) but high in Namibia (0.48; 0.16-10.17), Eswatini (0.64; 0.23-11.8) and South Africa (1.21; 0.83-9.84). The combination of high fragility of ART programmes and high ART coverage levels was associated with a sharp increase in pretreatment NNRTI resistance. CONCLUSIONS: This comparison of nine countries shows that pretreatment NNRTI resistance can be controlled despite high ART coverage levels. This was the case in Botswana, Mozambique, and Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART.
dc.format.mediumElectronic
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAntiretroviral therapy
dc.subjectEpidemiology
dc.subjectHIV drug resistance
dc.subjectHealth system science
dc.subjectModelling
dc.subjectSouthern Africa
dc.subjectBayes Theorem
dc.subjectDNA-Directed RNA Polymerases
dc.subjectDrug Resistance, Viral
dc.subjectHIV Infections
dc.subjectHIV-1
dc.subjectHumans
dc.subjectSouth Africa
dc.titleDrivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study.
dc.typeArticle
dc.publisher.departmentDepartment of Medicine
dc.date.updated2021-12-21T11:38:49Z
prism.issueIdentifier1
prism.number1042
prism.publicationDate2021
prism.publicationNameBMC Infect Dis
prism.startingPage1042
prism.volume21
dc.identifier.doi10.17863/CAM.79210
dcterms.dateAccepted2021-10-01
rioxxterms.versionofrecord10.1186/s12879-021-06757-6
rioxxterms.versionVoR
dc.contributor.orcidGupta, Ravindra [0000-0001-9751-1808]
dc.identifier.eissn1471-2334
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-10-07
cam.depositDate2021-12-21
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International