title: Antiviral effect of raltegravir on HTLV-1 carriers.
abstract: BACKGROUND
  In vitro studies support that integrase inhibitors, such as raltegravir, may inhibit human T cell lymphotropic virus type 1 (HTLV-1) replication. However, this hypothesis has not been tested in vivo.
  
  
  METHODS
  HTLV-1-infected individuals were invited to participate in a pilot, open study that examined whether 400 mg of raltegravir twice daily could exhibit any recognizable virological effect over 12 months. Proviral DNA was measured by a real-time PCR targeting the pol region. HTLV-1 integrase sequences were obtained from peripheral blood mononuclear cells (PBMCs) at baseline and during follow-up.
  
  
  RESULTS
  A total of five HTLV-1-infected individuals entered the study. All were infected with HTLV-1 subtype a. Two patients had HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the rest being asymptomatic. The HTLV-1 proviral load was high in all cases (median 758 HTLV-1 DNA copies/10(4) PBMCs). Following the initiation of raltegravir therapy and for up to 6 months, both of the HAM/TSP patients experienced a transient decline in the HTLV-1 proviral load (2248 to 519 and 1033 to 861 copies/10(4) PBMCs, respectively), returning to baseline levels on subsequent determinations. No significant changes in the HTLV-1 proviral load were noticed in the three asymptomatic individuals (median proviral load of 755 copies/10(4) PBMCs over time). A total of 20 integrase sequences could be obtained from the five patients, and no genotypic substitutions were recognized comparing baseline and follow-up specimens under raltegravir.
  
  
  CONCLUSIONS
  Treatment with raltegravir in HTLV-1-infected individuals does not result in a significant reduction of proviral load beyond 6 months of therapy. The lack of continuous viral replication cycles in chronic HTLV-1 carriers most likely explains our findings.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain. ana.trevino.rc@gmail.com
authors.forename: Ana
authors.initials: A
authors.lastname: Treviño
authors.forename: Patricia
authors.initials: P
authors.lastname: Parra
authors.forename: Tamara
authors.initials: T
authors.lastname: Bar-Magen
authors.forename: Carolina
authors.initials: C
authors.lastname: Garrido
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D002353:Carrier State / Q000188:drug therapy*; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D015490:HTLV-I Infections / Q000188:drug therapy*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011533:Proviruses / Q000302:isolation & purification; D011760:Pyrrolidinones / Q000008:administration & dosage*; D000068898:Raltegravir Potassium; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium