Smith RJ, Okano JT, Kahn JS, Bodine EN, Blower S. Evolutionary dynamics of complex networks of HIV drug-resistant strains: the case of San Francisco

Center for Biomedical Modeling, Semel Institute of Neuroscience & Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA.
Science (Impact Factor: 33.61). 02/2010; 327(5966):697-701. DOI: 10.1126/science.1180556
Source: PubMed


Over the past two decades, HIV resistance to antiretroviral drugs (ARVs) has risen to high levels in the wealthier countries of the world, which are able to afford widespread treatment. We have gained insights into the evolution and transmission dynamics of ARV resistance by designing a biologically complex multistrain network model. With this model, we traced the evolutionary history of ARV resistance in San Francisco and predict its future dynamics. By using classification and regression trees, we identified the key immunologic, virologic, and treatment factors that increase ARV resistance. Our modeling shows that 60% of the currently circulating ARV-resistant strains in San Francisco are capable of causing self-sustaining epidemics, because each individual infected with one of these strains can cause, on average, more than one new resistant infection. It is possible that a new wave of ARV-resistant strains that pose a substantial threat to global public health is emerging.

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Available from: Sally Blower, Feb 28, 2014
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    • "Failure to properly adhere to such medication is responsible for the development of drug resistance, which can render ARVs less effective [8]. Furthermore, resistant strains can subsequently be transmitted to newly infected individuals, who will not respond to treatment [9]. A variety of mathematical models are in agreement that the prevalence of drug resistance will increase in resource-constrained countries as a result of preexposure prophylaxis [10] [11] [12], although other studies have suggested that the development of resistance may be offset by the number of infections averted in the first place [13]. "
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    • "The introduction of highly active antiretroviral therapy (HAART) has significantly decreased morbidity and mortality among HIV-1-infected patients with access to these drugs. However, the development of drug resistance and issues related to drug tolerability and compliance often pose a considerable challenge to current therapies [4-8]. These concerns, together with recent reports of failure in clinical trials of HIV vaccines and several microbicides, reinforce the critical need to identify new targets for the development of novel classes of anti-HIV-1 drugs. "
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    • "Fourth, an analysis of RC does not account for the emergence and transmission of drug-resistant strains. When resistance emerges, multiple Rc's need to be evaluated in order to determine if elimination is (theoretically) possible [12], [13], [17] In addition, it needs to be understood the conditions that reduce RC to below one (e.g., the degree of viral suppression that reduces infectivity to 96%) would need to be continuously maintained until all of the treated individuals have died. Incidence would increase if the necessary conditions were not continuously maintained. "
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