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2021-12-23Zeitschriftenartikel
Numerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemes
dc.contributor.authorZhang, Lanxin
dc.contributor.authorWang, Junyu
dc.contributor.authorvon Kleist, Max
dc.date.accessioned2023-11-17T14:17:23Z
dc.date.available2023-11-17T14:17:23Z
dc.date.issued2021-12-23none
dc.identifier.other10.1371/journal.pcbi.1009295
dc.identifier.urihttp://edoc.rki.de/176904/11366
dc.description.abstractPre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the clin- ical efficacy is approximated. However, many stochastic simulations are needed to reduce the associated sampling error. To remedy the shortcomings of stochastic simulation, we developed a numerical method that allows predicting the efficacy of arbitrary prophylactic regimen directly from a viral dynamics model, without sampling. We apply the method to var- ious hypothetical dolutegravir (DTG) prophylaxis scenarios. The approach is verified against state-of-the-art stochastic simulation. While the method is more accurate than stochastic simulation, it is superior in terms of computational performance. For example, a continuous 6-month prophylactic profile is computed within a few seconds on a laptop computer. The method’s computational performance, therefore, substantially expands the horizon of feasi- ble analysis in the context of PrEP, and possibly other applications.eng
dc.description.abstractPre-exposure prophylaxis (PrEP) is an important tool to prevent HIV transmission. However, experimental identification of parameters that determine prophylactic efficacy is extremely difficult. Clues about these parameters could prove essential for the design of next-generation PrEP compounds. Integrative mathematical models can fill this void: Based on stochastic simulation, a sample statistic can be generated, from which the prophylactic efficacy is estimated. However, for this sample statistic to be accurate, many simulations need to be performed. Here, we introduce a numerical method to directly compute the prophylactic efficacy from a viral dynamics model, without the need for sampling. Based on several examples with dolutegravir (DTG) -based short- and long-term PrEP, as well as post-exposure prophylaxis we demonstrate the correctness of the new method and its outstanding computational performance. Due to the method’s computational performance, a number of analyses, including formal sensitivity analysis, are becoming feasible with the proposed method.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectprophylaxiseng
dc.subjectpharmacokineticseng
dc.subjectpre-exposure prophylaxiseng
dc.subjectHIVeng
dc.subjectpost-exposure prophylaxiseng
dc.subjectviral replicationeng
dc.subjectT cellseng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleNumerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemesnone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/11366-9
dc.type.versionupdatedVersionnone
local.edoc.container-titlePLOS Computational Biologynone
local.edoc.container-issn1553-7358none
local.edoc.pages24none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://journals.plos.org/ploscompbiol/none
local.edoc.container-publisher-namePLOSnone
local.edoc.container-reportyear2021none
dc.description.versionPeer Reviewednone

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