title: Topical cidofovir to treat high-grade anal intraepithelial neoplasia in HIV-infected patients: a pilot clinical trial.
abstract: OBJECTIVE
  To evaluate the efficacy of 1% topical cidofovir cream for the treatment of anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals.
  
  
  METHODS
  Single-arm, open-label, pilot clinical trial.
  
  
  METHODS
  The study medication was applied intraanally three times per week for 4 weeks. Lesions were assessed with high-resolution anoscopy and biopsy at weeks 12 and 24. The primary endpoint was complete remission (CR) at week 12, defined as clinical and histological remission. We also evaluated partial remission defined as regression to low-grade squamous intraepithelial lesion.
  
  
  RESULTS
  We included 17 HIV-infected patients with intraanal HSIL. Median (interquartile range) age was 36 years (28-41), median (interquartile range) CD4 cell count was 545 cells/μl (358-630), and viral load was less than 50  copies/ml in 93.7%. Two patients were lost to follow-up, one of them did not apply treatment. At 12 weeks, in the intention-to-treat population, 10 out of 16 patients [62.5%; 95% confidence interval (CI), 38.2-85.7%] had achieved CR. At 24 weeks, seven of the 10 patients (70%; 95% CI, 47-93%) remained in CR, but two out of 10 patients (20%; 95% CI, 0-40%) presented HSIL. One patient did not attend the visit at 24 weeks. Three patients with persistent HSIL at 12 weeks improved at 24 weeks (partial response in one and CR in two). The mean number of human papillomavirus genotypes decreased from 5.2 to 2.7 at 12 weeks (P = 0.002). Local adverse effects were frequent (81%), although there were no discontinuations because of adverse events.
  
  
  CONCLUSIONS
  One percent topical cidofovir could be an appropriate alternative therapy in HIV-infected patients with anal HSIL.
  
  
  BACKGROUND
  gov unique identifier: NCT01946009.
authors.affiliation: aDepartment of DermatologybDepartment of Internal Medicine, Hospital Universitario La Paz-IdiPazcDepartment of ColoproctologydDepartment of Pathology, Hospital Universitario La PazeDepartment of Infectious Diseases, Hospital Universitario Ramon y Cajal, IRYCISfFundación SEIMC-GESIDAgBiostatistics Unit, Hospital Universitario La Paz-IdiPaz, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Sendagorta
authors.forename: Jose I
authors.initials: JI
authors.lastname: Bernardino
authors.forename: Mario
authors.initials: M
authors.lastname: Álvarez-Gallego
authors.forename: Marta
authors.initials: M
authors.lastname: Feíto
authors.forename: Rosa
authors.initials: R
authors.lastname: Feltes
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Beato
authors.forename: Jose A
authors.initials: JA
authors.lastname: Pérez-Molina
authors.forename: Maria
authors.initials: M
authors.lastname: Yllescas
authors.forename: Mariana
authors.initials: M
authors.lastname: Díaz-Almirón
authors.forename: Jose R
authors.initials: JR
authors.lastname: Arribas
authors.forename: Juan
authors.initials: J
authors.lastname: González-García
authors.forename: Pedro
authors.initials: P
authors.lastname: Herranz
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D001005:Anus Neoplasms / Q000188:drug therapy*; D001706:Biopsy; D002278:Carcinoma in Situ / Q000188:drug therapy*; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage*; D030361:Papillomavirus Infections / Q000150:complications* / Q000188:drug therapy*; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir