title: The impact of antiretroviral therapy on population-level virulence evolution of HIV-1.
abstract: 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.
authors.affiliation: Nuffield Department of Clinical Medicine, The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK hannah.roberts@ndm.ox.ac.uk.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Roberts
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.affiliation: The Institute for Emerging Infections, The Oxford Martin School, Oxford OX1 3BD, UK Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: Angela R
authors.initials: AR
authors.lastname: McLean
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D019143:Evolution, Molecular; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D019562:Viral Load; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D044966:Anti-Retroviral Agents; D037521:Virulence Factors
keywords: HIV-1; antiretroviral therapy; between-host modelling; set point viral load; virulence evolution