title: Impact of Pill Sharing on Drug Resistance Due to a Wide-Scale Oral Prep Intervention in Generalized Epidemics.
abstract: BACKGROUND
  The first antiretroviral drug (Truvada) to be used as a pre-exposure prophylaxis (PrEP) in preventing HIV transmission is about to be approved. Behavioral studies suggest that a portion of users may share anti-retroviral drugs with sex partners, family, or friends. Pill sharing will decrease PrEP efficacy and adherence level, and potentially create an environment favorable for the development of drug resistance. We aim to evaluate the potential impact of pill sharing on the PrEP effectiveness and on the rates of drug-resistance development in heterosexual populations.
  
  
  METHODS
  A transmission dynamic model was used to assess the population-level impact of oral PrEP. The fractions of new HIV infections prevented (CPF), drug resistance prevalence and the proportion of new infections in which drug-resistant HIV is transmitted (TDR) are evaluated over fixed time periods. The influence of different factors on CPF and TDR is studied through simulations, using epidemic parameters representative of the countries in Sub-Saharan Africa.
  
  
  RESULTS
  Without pill sharing, a 70% efficacious PrEP used consistently by 60% of uninfected individuals prevents 52.8% (95% CI 49.4%-56.4%) of all new HIV infections over ten years with drug-resistant HIV transmitted in 2.2% of the new infections. Absolute CPF may vary by 9% if up to 20% of the users share PrEP while the level of TDR and total resistance prevalence may increase by up to 6-fold due to pill sharing in some intervention scenarios.
  
  
  CONCLUSIONS
  Pill sharing may increase the PrEP coverage level achieved in the population but it also affects the PrEP efficacy for the users who do not follow the prescribed schedule. More importantly, it creates a pool of untracked users who remain unreached by the effort to avoid sub-optimal PrEP usage by infected people. This increases substantially the potential risk of drug resistance in the population.
authors.affiliation: Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, USA.
authors.forename: Dobromir
authors.initials: D
authors.lastname: Dimitrov
authors.affiliation: Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Boily
authors.affiliation: CHU Sainte-Justine Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Benoît R
authors.initials: BR
authors.lastname: Mâsse
authors.affiliation: Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Brown
keywords: HIV; Pill sharing; Pre-exposure prophylaxis