Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study

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dc.contributor.authorRiou, Julien
dc.contributor.authorDupont, Carole
dc.contributor.authorBertagnolio, Silvia
dc.contributor.authorGupta, Ravindra K.
dc.contributor.authorKouyos, Roger D.
dc.contributor.authorEgger, Matthias
dc.contributor.authorL. Althaus, Christian
dc.date.accessioned2021-10-11T08:21:22Z
dc.date.available2021-10-11T08:21:22Z
dc.date.issued2021-10-07
dc.date.updated2021-10-10T03:10:53Z
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.en_US
dc.identifier.apacitationRiou, J., Dupont, C., Bertagnolio, S., Gupta, Ravindra K., Kouyos, Roger D., Egger, M., & (2021). Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study. <i>BMC Infectious Diseases</i>, 21(Article number: 1042), http://hdl.handle.net/11427/35140en_ZA
dc.identifier.chicagocitationRiou, Julien, Carole Dupont, Silvia Bertagnolio, Ravindra K. Gupta, Roger D. Kouyos, Matthias Egger, and "Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study." <i>BMC Infectious Diseases</i> 21, Article number: 1042. (2021) http://hdl.handle.net/11427/35140en_ZA
dc.identifier.citationRiou, J., Dupont, C., Bertagnolio, S., Gupta, Ravindra K., Kouyos, Roger D., Egger, M. & 2021. Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study. <i>BMC Infectious Diseases.</i> 21(Article number: 1042) http://hdl.handle.net/11427/35140en_ZA
dc.identifier.ris TY - Journal Article AU - Riou, Julien AU - Dupont, Carole AU - Bertagnolio, Silvia AU - Gupta, Ravindra K. AU - Kouyos, Roger D. AU - Egger, Matthias AU - L. Althaus, Christian AB - Introduction 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. DA - 2021-10-07 DB - OpenUCT DP - University of Cape Town IS - Article number: 1042 J1 - BMC Infectious Diseases KW - HIV drug resistance KW - Epidemiology KW - Southern Africa KW - Antiretroviral therapy KW - Health system science KW - Modelling LK - https://open.uct.ac.za PY - 2021 T1 - Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study TI - Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study UR - http://hdl.handle.net/11427/35140 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12879-021-06757-6
dc.identifier.urihttp://hdl.handle.net/11427/35140
dc.identifier.vancouvercitationRiou J, Dupont C, Bertagnolio S, Gupta Ravindra K, Kouyos Roger D, Egger M, et al. Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study. BMC Infectious Diseases. 2021;21(Article number: 1042) http://hdl.handle.net/11427/35140.en_ZA
dc.language.isoenen_US
dc.language.rfc3066en
dc.publisher.departmentCentre for Infectious Disease Epidemiology and Research (CIDER)en_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.holderThe Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceBMC Infectious Diseasesen_US
dc.source.journalissueArticle number: 1042en_US
dc.source.journalvolume21en_US
dc.source.urihttps://bmcinfectdis.biomedcentral.com/
dc.subjectHIV drug resistanceen_US
dc.subjectEpidemiologyen_US
dc.subjectSouthern Africaen_US
dc.subjectAntiretroviral therapyen_US
dc.subjectHealth system scienceen_US
dc.subjectModellingen_US
dc.titleDrivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling studyen_US
dc.typeJournal Articleen_US
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