Antiretroviral dynamics determines HIV evolution and predicts therapy outcome

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Antiretroviral dynamics determines HIV evolution and predicts therapy outcome

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Title: Antiretroviral dynamics determines HIV evolution and predicts therapy outcome
Author: Rosenbloom, Daniel Scholes; Hill, Alison Lynn; Rabi, S. Alireza; Siliciano, Robert F.; Nowak, Martin A.

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Citation: Rosenbloom, 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.
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Abstract: Despite 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.
Published Version: doi:10.1038/nm.2892
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490032/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10861169
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