title: Evaluation of progressive multifocal leukoencephalopathy treatments in a Spanish cohort of HIV-infected patients: do protease inhibitors improve survival regardless of central nervous system penetration-effectiveness (CPE) score?
abstract: OBJECTIVE
  The aim of the study was to investigate whether survival after progressive multifocal leukoencephalopathy (PML) diagnosis in HIV-1-infected patients was associated with central nervous system penetration-effectiveness (CPE) score and the presence or absence of protease inhibitors in the treatment regimen.
  
  
  METHODS
  In the absence of treatments demonstrated to be effective for PML in HIV-1-infected patients and in the light of the controversy surrounding the use of CPE scores to make decisions on treatment after diagnosis, we determined whether there were differences in survival at 1 year depending on the type and characteristics of treatment. A multicentre retrospective observational study including three Spanish hospitals was carried out for the period from 1 January 1994 to 31 December 2009. Patients with a PML diagnosis were included in the study if they were symptomatic and met at least two of the following three criteria: (1) compatible radiological findings; (2) a positive polymerase chain reaction for John Cunningham virus (JCV) in the cerebrospinal fluid (CSF); (3) an absence of findings suggesting another infection in the central nervous system, after general CSF cultures for virus, bacteria and mycobacteria.
  
  
  RESULTS
  A total of 98 patients were included in the study; 24.5% were diagnosed in the period 1994-1999, 39.8% in 2000-2004 and 35.7% in 2005-2009. The median follow-up time was 363 days (interquartile range 108-1946 days). The median CD4 count was 76 cells/uL (interquartile range 30-166 cells/uL) and 62% of patients had an HIV viral load >50 HIV-1 RNA copies/ml. Thirty-eight per cent of patients received high-penetrance treatment, and 58% received treatment that included protease inhibitors. In the analysis of survival at 1 year, a higher CPE score did not result in an improvement in survival, but the presence of protease inhibitors in the regimen was associated with a statistically significant (P = 0.03) reduction in mortality (hazard ratio 0.40; 95% confidence interval 0.18-0.91).
  
  
  CONCLUSIONS
  We consider that the lower mortality observed in the protease inhibitor group may be clinically relevant, and, if this is the case, a treatment based on protease inhibitors may be indicated for patients diagnosed with PML.
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Son Espases, Carretera de Valldemosa SN, Palma de Mallorca, Illes Balears, Spain. ffanjul@gmail.com
authors.forename: F
authors.initials: F
authors.lastname: Fanjul
authors.forename: M
authors.initials: M
authors.lastname: Riveiro-Barciela
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez
authors.forename: E
authors.initials: E
authors.lastname: Delgado
authors.forename: J
authors.initials: J
authors.lastname: Murillas
authors.forename: A
authors.initials: A
authors.lastname: Payeras Cifré
authors.forename: V
authors.initials: V
authors.lastname: Falcó
authors.forename: M
authors.initials: M
authors.lastname: Riera
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000328:Adult; D018791:CD4 Lymphocyte Count; D002490:Central Nervous System / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D011379:Prognosis; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D011480:Protease Inhibitors; D012367:RNA, Viral