title: Antiretroviral therapy interruptions result in loss of protective humoral immunity to neoantigens in HIV-infected individuals.
abstract: OBJECTIVE
  Sustained antiretroviral therapy (ART)-mediated viral suppression restores responses to vaccination in HIV-1-infected individuals. As ART interruption occur frequently in resource-constrained settings, we studied their effects on the ability to mount humoral immune responses against a neoantigen.
  
  
  METHODS
  Treatment-naive HIV-1-infected individuals were treated with stavudine, lamuvidine and lopinavir/ritonovir. Individuals who maintained viral load less than 50  copies/ml and CD4 T-cell counts more than 450  cells/μl for 6 months received three doses of rabies vaccine, and were randomized to 72 weeks of continuous ART (arm 1) or sequential 2, 4 and 8-week ART interruptions (arm 2). An additional vaccine dose was administered at study end.
  
  
  METHODS
  Neutralizing antibody titers to rabies virus were assessed in plasma with a rapid fluorescent focus-inhibiting test.
  
  
  RESULTS
  The proportion of participants achieving protective (>0.5 IU/ml) antibody titer after vaccination was similar (arm 1=92%; arm 2=91%), but over time the cumulative proportion of observations with protective titer was greater in arm 1 than arm 2 (P=0.0177). From week 26 after vaccination, antibody titers were lower in arm 2 than arm 1, and volunteers in arm 2 lost protective antibody titers at a greater rate (P=0.0029). After boosting, 100% of arm 1 and 95% arm 2 volunteers achieved protective antibody titer.
  
  
  CONCLUSIONS
  Our data indicate that individuals undergoing recurring ART interruption retain lower neutralizing antibody titers to a neoantigen, but maintain the ability to mount secondary responses upon boosting, suggesting that they might benefit from vaccine schedule intensification.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Livio
authors.initials: L
authors.lastname: Azzoni
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Foulkes
authors.forename: Cynthia
authors.initials: C
authors.lastname: Firnhaber
authors.forename: Xiangfan
authors.initials: X
authors.lastname: Yin
authors.forename: Zhi Q
authors.initials: ZQ
authors.lastname: Xiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
authors.forename: Robert
authors.initials: R
authors.lastname: Gross
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D000328:Adult; D017954:Africa South of the Sahara; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes; D004334:Drug Administration Schedule; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D061466:Lopinavir / Q000008:administration & dosage; D008213:Lymphocyte Activation; D008297:Male; D019438:Ritonavir / Q000008:administration & dosage; D018119:Stavudine / Q000008:administration & dosage; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D001324:Autoantigens; D061466:Lopinavir; D018119:Stavudine; D019438:Ritonavir