title: How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact.
abstract: BACKGROUND
  Randomized controlled trials reported that pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance.
  
  
  METHODS
  We surveyed expert virologists with questions about biological assumptions regarding drug resistance due to PrEP use. The influence of these assumptions on the prevalence of drug resistance and the fraction of HIV transmitted resistance was studied with a mathematical model. For comparability, 50% PrEP-coverage of and 90% per-act efficacy of PrEP in preventing HIV acquisition are assumed in all simulations.
  
  
  RESULTS
  Virologists disagreed on the following: the time until resistance emergence (range: 20-180 days) in infected PrEP users with breakthrough HIV infections; the efficacy of PrEP against drug-resistant HIV (25%-90%); and the likelihood of resistance acquisition upon transmission (10%-75%). These differences translate into projections of 0.6%- 1% and 3.5%-6% infected individuals with detectable resistance 10 years after introducing PrEP, assuming 100% and 50% adherence, respectively. The rate of resistance emergence following breakthrough HIV infection and the rate of resistance reversion after PrEP use is discontinued, were the factors identified as most influential on the expected resistance associated with PrEP. Importantly, 17-23% infected individuals could virologically fail treatment as a result of past PrEP use or transmitted resistance to PrEP with moderate adherence.
  
  
  CONCLUSIONS
  There is no broad consensus on quantification of key biological processes that underpin the emergence of PrEP-associated drug resistance. Despite this, the contribution of PrEP use to the prevalence of the detectable drug resistance is expected to be small. However, individuals who become infected despite the use of PrEP should be closely monitored due to higher risk of virological failure when initiating antiretroviral treatment in the future.
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|Department of Applied Mathematics, University of Washington, Seattle, Washington, United States of America.
authors.forename: Dobromir T
authors.initials: DT
authors.lastname: Dimitrov
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Boily
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Hallett
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Albert
authors.affiliation: Department of Virology, Erasmus Medical Centre, University Medical Centre Rotterdam, Rotterdam, Netherlands.
authors.forename: Charles
authors.initials: C
authors.lastname: Boucher
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.affiliation: Research Department of Infection, University College Medical School, London, United Kingdom.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.affiliation: Department of Virology, Erasmus Medical Centre, University Medical Centre Rotterdam, Rotterdam, Netherlands.
authors.forename: David A M C
authors.initials: DA
authors.lastname: van de Vijver
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008962:Models, Theoretical; D065129:Pre-Exposure Prophylaxis; D011634:Public Health; D016032:Randomized Controlled Trials as Topic; D014773:Virology
chemical_list: D019380:Anti-HIV Agents