title: Impact of circulating resistance-associated mutations on HIV pre-exposure prophylaxis (PrEP) efficacy: Modeling from antiretroviral resistance cohort analysis (ARCA) national database.
abstract: PrEP with FTC/TDF has shown great efficacy in preventing new HIV infections but issues remain (low adherence, high costs, toxicity and resistance development). No data are available about the impact of circulating Resistance-Associated Mutations (RAMs) on its efficacy.
  
  
  
  describe the prevalence of FTC and/or TDF-related RAMs in Italian HIV-infected population and their potential impact on PrEP efficacy.
  
  
  
  ARCA is a national database that collects data about RAMs and epidemiological correlates from sites throughout Italy; it was queried about the prevalence of these RAMs in the last decade. PrEP efficacy was adjusted for a dynamic score based on RAMs prevalence. Absolute and relative risk increases (ARI and RRI) and number needed to harm (NNH) were calculated after this score.
  
  
  
  the query retrieved 3579 HAART-naïve and 5781 experienced subjects. Resistance to TDF is low and more common among naïve MSM in the area of Milan (where it topped to 14.3%), without other significant differences. If good adherence is not attained, RRI for receptive anal sex increases by 16% (in naïve) and 93.4% (in experienced MSM). NNH is largely above 10000 except for having receptive anal sex with a HAART-experienced MSM on a failing treatment (970).
  
  
  
  according to this model, PrEP may be introduced in Italy without general concerns, but efficacy may be partly reduced in young MSM having sex in Rome and Milan.
authors: Infectious Diseases Department, ASST GOM "Niguarda", Milan, Italy. Electronic address: Roberto.rossotti@ospedaleniguarda.it.
authors: Roberto
authors: R
authors: Rossotti
authors: Infectious Diseases Clinics, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors: Vanni
authors: V
authors: Borghi
authors: Laboratory of Virology and Microbiology, AO Papa Giovanni XXIII Bergamo, Bergamo, Italy.
authors: Anna Paola
authors: AP
authors: Callegaro
authors: Clinical Microbiology, Virology and Bioemergency, Luigi Sacco Hospital, Milan, Italy.
authors: Valeria
authors: V
authors: Micheli
authors: Hygiene Unit, IRCSS A.O.U. San Martino-IST, Genoa, Italy.
authors: Bianca
authors: B
authors: Bruzzone
authors: Laboratory of Virology, Careggi Hospital, Florence, Italy.
authors: Grazia
authors: G
authors: Colao
authors: Clinical Microbiology, Virology and Bioemergency, Luigi Sacco Hospital, Milan, Italy.
authors: Maria Rita
authors: MR
authors: Gismondo
authors: Department of Medical Biotechnologies, University of Siena, Italy.
authors: Ilaria
authors: I
authors: Vicenti
authors: Infectious Diseases Department, Ente Ospedaliero Ospedali Galliera, Genoa, Italy.
authors: Giovanni
authors: G
authors: Penco
authors: Department of Medical Biotechnologies, University of Siena, Italy.
authors: Maurizio
authors: M
authors: Zazzi
authors: Clinic of Infectious Diseases, DIBIC Luigi Sacco, Milan, Italy.
authors: Stefano
authors: S
authors: Rusconi
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D000068679:Emtricitabine / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D065129:Pre-Exposure Prophylaxis / Q000706:statistics & numerical data*; D012306:Risk; D000068698:Tenofovir / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D044966:Anti-Retroviral Agents; D000068698:Tenofovir; D000068679:Emtricitabine
keywords: HIV; MSM; PrEP; Resistance-associated mutations