title: Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure: a pilot randomised trial.
abstract: BACKGROUND
  In HIV-1-infected patients harbouring the M184V mutation (M184V), lamivudine monotherapy leads to a smaller decrease in CD4 percentages (CD4%) than treatment interruption, possibly due to the reduced fitness of the mutated virus.
  
  
  OBJECTIVE
  We assessed whether a minimal dose of a cytidine analogue that is theoretically sufficient to maintain M184V (one emtricitabine tablet once-weekly) may be as effective.
  
  
  METHODS
  In a proof-of-concept, randomised clinical trial, HIV-1-infected patients with CD4 cells >400/mm(3), failing on lamivudine- or emtricitabine-containing combination antiretroviral therapy (cART), received emtricitabine once-a-week (A), or emtricitabine once-a-day (B), or lamivudine once-a-day (C). The primary endpoint was the proportion of subjects without a 12-week loss in CD4%. The patients resumed cART after 24 weeks or in the case of CD4 cells <350/mm(3).
  
  
  RESULTS
  The 38 enrolled patients had similar baseline characteristics across groups. The primary endpoint was reached by 5/13 patients (38.5%) in arm A, 3/13 (23.1%) in arm B, and 3/12 (25%) in arm C (P=0.644), and respectively 4/13 (30.8%), 4/13 (30.8%) and 5/12 (41.7%) had to resume cART within 24 weeks (P=0.805). The immunological changes over 24 weeks were similar in the three groups, but there was a higher median viral rebound in once-weekly treatment recipients (A) than in once-daily (B+C): 0.97 versus 0.52log(10)copies/ml (P=0.033). M184V was maintained in all the participants.
  
  
  CONCLUSIONS
  Once-weekly emtricitabine led to a higher viral rebound than once-daily monotherapy, but similar immunological changes, thus suggesting a role of M184V in slowing the decrease in CD4% in treatment failing subjects.
authors.affiliation: Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy. a.soria@hsgerardo.org
authors.forename: Alessandro
authors.initials: A
authors.lastname: Soria
authors.forename: Anna
authors.initials: A
authors.lastname: Danise
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.forename: Simon
authors.initials: S
authors.lastname: Tiberi
authors.forename: Elena
authors.initials: E
authors.lastname: Seminari
authors.forename: Francesca
authors.initials: F
authors.lastname: Cossarini
authors.forename: Alba
authors.initials: A
authors.lastname: Bigoloni
authors.forename: Simone
authors.initials: S
authors.lastname: Marcotullio
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016879:Salvage Therapy / Q000379:methods*; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D003841:Deoxycytidine; D000068679:Emtricitabine