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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/316| The Impact of Scaling up Dolutegravir on Antiretroviral Resistance in South Africa | |
| Katharina Kusejko Roger D Kouyos Gilles Wandeler Julien Riou Huldrych F Gunthard Leigh F Johnson Matthias Egger Anthony Hauser | |
| Novel Coronavirus | |
| Acceso Abierto | |
| Atribución | |
| 10.1101/19010132 | |
| Background: Rising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG's high genetic barrier to resistance. We used mathematical modelling to examine the impact of the scale-up of DTG-based ART on NNRTI pre-treatment drug resistance (PDR) in South Africa, 2019-2040. Methods and results: We adapted the MARISA (Modelling Antiretroviral drug Resistance In South Africa) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modelled the introduction of DTG in 2019 under two scenarios: DTG as first-line regimen for ART-initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Due to safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to i) women beyond reproductive age, ii) women beyond reproductive age or using contraception, and iii) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI resistance in all scenarios if both ART initiators are started on a DTG-based regimens and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI resistance would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI resistance from 58.5% (without DTG) to 14.8% (with universal DTG) in 2040. If all men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI resistance would reach 35.1% in 2040. Conclusions: Our model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would slow down the increase in levels of NNRTI resistance. ### Competing Interest Statement HFG has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Sandoz and Mepha. ### Funding Statement This study was supported by the National Institutes of Health (www.nih.gov) (National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; grant number 2U01AI069924 to ME) and the Swiss National Science Foundation (Grant No. 174281 to ME). RDK was supported by the Swiss National Science Foundation (Grant number BSSGI0_155851). ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Not Applicable Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Not Applicable Some restrictions will apply. | |
| Cold Spring Harbor Laboratory Press | |
| 2019 | |
| Preimpreso | |
| https://www.medrxiv.org/content/10.1101/19010132v1 | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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| The Impact of Scaling up.pdf | 603.29 kB | Adobe PDF | Visualizar/Abrir |