title: Improved survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy receiving early 5-drug combination antiretroviral therapy.
abstract: BACKGROUND
  Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery.
  
  
  RESULTS
  All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008).
  
  
  CONCLUSIONS
  The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00120367.
authors: Service de Médecine Interne et de Maladies Infectieuses, Hôpital Universitaire de Bicêtre-Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicêtre, France. jacques.gasnault@bct.aphp.fr
authors: Jacques
authors: J
authors: Gasnault
authors: Dominique
authors: D
authors: Costagliola
authors: Houria
authors: H
authors: Hendel-Chavez
authors: Anne
authors: A
authors: Dulioust
authors: Sophie
authors: S
authors: Pakianather
authors: Anne-Aurélie
authors: AA
authors: Mazet
authors: Marie-Ghislaine
authors: MG
authors: de Goer de Herve
authors: Rémi
authors: R
authors: Lancar
authors: Anne-Sophie
authors: AS
authors: Lascaux
authors: Lydie
authors: L
authors: Porte
authors: Jean-François
authors: JF
authors: Delfraissy
authors: Yassine
authors: Y
authors: Taoufik
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality* / Q000821:virology; D006801:Humans; D007577:JC Virus / Q000187:drug effects / Q000472:pathogenicity; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy* / Q000401:mortality* / Q000821:virology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use; D016133:Polymerase Chain Reaction
chemical_list: D044966:Anti-Retroviral Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide