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dc.contributor.authorRosenbloom, Daniel Scholes
dc.contributor.authorHill, Alison Lynn
dc.contributor.authorRabi, S. Alireza
dc.contributor.authorSiliciano, Robert F.
dc.contributor.authorNowak, Martin A.
dc.date.accessioned2013-07-09T17:08:32Z
dc.date.issued2012
dc.identifier.citationRosenbloom, Daniel I. S., Alison L. Hill, S. Alireza Rabi, Robert F. Siliciano, and Martin A. Nowak. 2012. Antiretroviral dynamics determines HIV evolution and predicts therapy outcome. Nature medicine 18(9): 1378-1385.en_US
dc.identifier.issn1078-8956en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10861169
dc.description.abstractDespite the high inhibition of viral replication achieved by current anti-HIV drugs, many patients fail treatment, often with emergence of drug-resistant virus. Clinical observations show that the relationship between adherence and likelihood of resistance differs dramatically across drug class. We developed a mathematical model that explains these observations and makes novel predictions. Our model incorporates drug properties, fitness differences between susceptible and resistant strains, mutation, and adherence. We show that antiviral activity falls quickly for drugs with sharp dose-response curves and short half-lives, such as boosted protease inhibitors, limiting the time when resistance can be selected. We find that poor adherence to such drugs causes failure via growth of susceptible virus, explaining puzzling clinical observations. Furthermore, our model predicts that certain single-pill combination therapies can prevent resistance regardless of patient adherence. Our approach represents a first step for simulating clinical trials and may help select novel drug regimens for investigation.en_US
dc.description.sponsorshipMathematicsen_US
dc.description.sponsorshipPhysicsen_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/nm.2892en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490032/pdf/en_US
dash.licenseLAA
dc.titleAntiretroviral dynamics determines HIV evolution and predicts therapy outcomeen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalNature Medicineen_US
dash.depositing.authorNowak, Martin A.
dc.date.available2013-07-09T17:08:32Z
dc.identifier.doi10.1038/nm.2892*
dash.contributor.affiliatedRosenbloom, Daniel Scholes
dash.contributor.affiliatedHill, Alison
dash.contributor.affiliatedNowak, Martin


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