title: Factors associated with viral rebound in HIV-1-infected individuals enrolled in a therapeutic HIV-1 gag vaccine trial.
abstract: BACKGROUND
  Human immunodeficiency virus type 1 (HIV-1) vaccines directed to the cell-mediated immune system could have a role in lowering the plasma HIV-1 RNA set point, which may reduce infectivity and delay disease progression.
  
  
  METHODS
  Randomized, placebo-controlled trial involving HIV-1-infected participants who received a recombinant adenovirus serotype 5 (rAd5) HIV-1 gag vaccine or placebo. Sequence-based HLA typing was performed for all 110 participants who initiated analytic treatment interruption (ATI) to assess the role of HLA types previously associated with HIV prognosis. Plasma HIV-1 gag and pol RNA sequences were obtained during the ATI. Virologic endpoints and HLA groups were compared between treatment arms using the 2-sample rank sum test. A linear regression model was fitted to derive independent correlates of ATI week 16 plasma viral load (w16 PVL).
  
  
  RESULTS
  Vaccinated participants with neutral HLA alleles had lower median w16 PVLs than did vaccinated participants with protective HLA alleles (P = .01) or placebo participants with neutral HLA alleles (P = .02). Factors independently associated with lower w16 PVL included lower pre-antiretroviral therapy PVL, greater Gag sequence divergence from the vaccine sequence, decreased proportion of HLA-associated polymorphisms in Gag, and randomization to the vaccine arm.
  
  
  CONCLUSIONS
  Therapeutic vaccination with a rAd5-HIV gag vaccine was associated with lower ATI week 16 PVL even after controlling for viral and host genetic factors.
  
  
  BACKGROUND
  NCT00080106.
authors.affiliation: Section of Retroviral Therapeutics, Brigham and Women's Hospital, Boston, Massachusetts 02139, USA.
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Li
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.forename: Hongying
authors.initials: H
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Spritzler
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000256:Adenoviridae / Q000235:genetics; D004337:Drug Carriers / Q000008:administration & dosage; D005822:Genetic Vectors; D015658:HIV Infections / Q000628:therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D006680:HLA Antigens; D010919:Placebos; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus