Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom; Department of Paediatrics, University of Oxford, Oxford, United Kingdom; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; Institute for Emerging Infections, Oxford Martin School, Oxford, United Kingdom; Department of Zoology, University of Oxford, Oxford, United Kingdom
Roberts, H.E., Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom; Goulder, P.J.R., Department of Paediatrics, University of Oxford, Oxford, United Kingdom, HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; McLean, A.R., Institute for Emerging Infections, Oxford Martin School, Oxford, United Kingdom, Department of Zoology, University of Oxford, Oxford, United Kingdom
In HIV-infected patients, an individual's set point viral load (SPVL) strongly predicts disease progression. Some think that SPVL is evolving, indicating that the virulence of the virus may be changing, but the data are not consistent. In addition, the widespread use of antiretroviral therapy (ART) has the potential to drive virulence evolution. We develop a simple deterministic model designed to answer the following questions: what are the expected patterns of virulence change in the initial decades of an epidemic? Could administration of ART drive changes in virulence evolution and, what is the potential size and direction of this effect? We find that even without ART we would not expect monotonic changes in average virulence. Transient decreases in virulence following the peak of an epidemic are not necessarily indicative of eventual evolution to avirulence. In the short term, we would expect widespread ART to cause limited downward pressure on virulence. In the long term, the direction of the effect is determined by a threshold condition, which we define. We conclude that, given the surpassing benefits of ART to the individual and in reducing onward transmission, virulence evolution considerations need have little bearing on how we treat. © 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Digital storage; Viruses; Antiretrovirals; Deterministic modeling; Disease progression; Downward pressure; HIV-1; Threshold condition; Viral load; Virulence evolution; Diseases; anti human immunodeficiency virus agent; antiviral therapy; Article; epidemic; human; Human immunodeficiency virus 1 infection; Human immunodeficiency virus infected patient; meta analysis; model; therapy effect; virus virulence