title: Evaluating the extent of potential resistance to pre-exposure prophylaxis within the UK HIV-1-infectious population of men who have sex with men.
abstract: OBJECTIVE
  Recent studies have shown that pre-exposure prophylaxis (PrEP) can substantially reduce the chance of acquiring HIV infection. However, PrEP efficacy has been found to be compromised in macaque studies if the challenge virus is antiretroviral therapy (ART)-resistant. Our objective was to evaluate the likelihood that a UK man who has sex with men (MSM) would be exposed to PrEP-resistant HIV in a homosexual encounter with an HIV-infectious partner.
  
  
  METHODS
  Data from the UK Collaborative HIV Cohort (UK CHIC) study were linked to the UK HIV Drug Resistance Database for HIV-1-positive MSM patients seen between 2005 and 2008. Patients were categorized as undiagnosed; diagnosed but ART-naïve; ART-experienced and on treatment; and ART-experienced and on a treatment interruption. Considering current PrEP regimens, resistance to (a) tenofovir (TDF) alone, (b) TDF and emtricitabine (FTC), and (c) TDF or FTC was estimated. Patients without resistance tests had PrEP resistance imputed using bootstrapping and logistic regression models.
  
  
  RESULTS
  The population-level prevalence of PrEP resistance in HIV-infectious individuals in 2008 was estimated to be 1.6, 0.9 and 4.1% for PrEP resistance definitions a, b and c, respectively. Prevalence in ART-experienced patients was highest, with negligible circulating resistance amongst ART-naïve individuals. The levels of resistance declined over the period of study.
  
  
  CONCLUSIONS
  Our analysis indicates low levels of resistance to proposed PrEP drugs. The estimated PrEP resistance prevalence in UK HIV-infected MSM is towards the lower range of values used in simulation studies which have suggested that circulating PrEP drug resistance will have a negligible impact on PrEP efficacy at the population level.
authors.affiliation: HIV and Infections Group,MRC Clinical Trials Unit, London, UK. did@ctu.mrc.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Dolling
authors.forename: A N
authors.initials: AN
authors.lastname: Phillips
authors.forename: V
authors.initials: V
authors.lastname: Delpech
authors.forename: D
authors.initials: D
authors.lastname: Pillay
authors.forename: P A
authors.initials: PA
authors.lastname: Cane
authors.forename: A M
authors.initials: AM
authors.lastname: Crook
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: E
authors.initials: E
authors.lastname: Fearnhill
authors.forename: T
authors.initials: T
authors.lastname: Hill
authors.forename: D
authors.initials: D
authors.lastname: Dunn
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000187:drug effects*; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D018451:Homosexuality, Male; D006801:Humans; D016015:Logistic Models; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D015995:Prevalence; D000068698:Tenofovir; D006113:United Kingdom / Q000453:epidemiology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine