Estimation of the HIV-1 Backward Mutation Rate From Transmitted Drug-Resistant Strains

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dc.contributor.authorKitayimbwa, John M.
dc.contributor.authorMugisha, Joseph Y. T.
dc.contributor.authorSaenz, Roberto A.
dc.date.accessioned2020-01-22T13:24:35Z
dc.date.available2020-01-22T13:24:35Z
dc.date.issued2016-12
dc.description.abstractOne of the serious threats facing the administration of antiretroviral therapy to human immunodeficiency virus (HIV-1) infected patients is the reported increasing prevalence of transmitted drug resistance. However, given that HIV-1 drug-resistant strains are often less fit than the wild-type strains, it is expected that drug-resistant strains that are present during the primary phase of the HIV-1 infection are replaced by the fitter wild-type strains. This replacement of HIV-1 resistant mutations involves the emergence of wild-type strains by a process of backward mutation. How quickly the replacement happens is dependent on the class of HIV-1 mutation group. We estimate the backward mutation rates and relative fitness of various mutational groups known to confer HIV-1 drug resistance. We do this by fitting a stochastic model to data for individuals who were originally infected by an HIV-1 strain carrying any one of the known drug resistance-conferring mutations and observed over a period of time to see whether the resistant strain is replaced. To do this, we seek a distribution, generated from simulations of the stochastic model, that best describes the observed (clinical data) replacement times of a given mutation. We found that Lamivudine/Emtricitabine-associated mutations have a distinctly higher, backward mutation rate and low relative fitness compared to the other classes (as has been reported before) while protease inhibitors-associated mutations have a slower backward mutation rate and high relative fitness. For the other mutation classes, we found more uncertainty in their estimates.en_US
dc.description.sponsorshipThe work was supported by a Wellcome Trust Uganda Ph.D. Fellowship in Infection and Immunity held by Kitayimbwa Mulindwa John, funded by a Wellcome Trust Strategic Award, grant number 084344.en_US
dc.identifier.citationKitayimbwa, J. M., Mugisha, J. Y. T., & Saenz, R. A. (2016). Estimation of the HIV-1 backward mutation rate from transmitted drug-resistant strains. Theoretical population biology, 112, 33-42.en_US
dc.identifier.urihttps://doi.org/10.1016/j.tpb.2016.08.001
dc.identifier.urihttps://hdl.handle.net/20.500.11951/855
dc.language.isoenen_US
dc.publisherTheoretical Population Biologyen_US
dc.relation.ispartofseries;Volume 112
dc.rightsAttribution-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-sa/3.0/us/*
dc.subjectBackward mutation rateen_US
dc.subjectWithin-host modelen_US
dc.subjectHIV-1en_US
dc.subjectVirus mutationsen_US
dc.subjectKaplan–Meier estimatesen_US
dc.titleEstimation of the HIV-1 Backward Mutation Rate From Transmitted Drug-Resistant Strainsen_US
dc.typeArticleen_US
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