title: Standard vaccines increase HIV-1 transcription during antiretroviral therapy.
abstract: Curative strategies using agents to perturb the HIV reservoir have demonstrated only modest activity, whereas increases in viremia after standard vaccination have been described. We investigated whether vaccination against non-HIV pathogens can induce HIV transcription and thereby play a role in future eradication strategies.
  
  
  
  A randomized controlled trial (NCT00329251) was performed to compare the effects of clinical vaccines with placebo on HIV transcription and immune activation.
  
  
  
  Twenty-six HIV-infected individuals on suppressive antiretroviral therapy were randomized to receive a vaccination schedule (n = 13) or placebo (n = 13). Cell-associated RNA and DNA were extracted from peripheral blood mononuclear cells, and HIV was quantified by droplet digital PCR using primers for gag and 2-LTR (for HIV DNA), unspliced gag RNA (gag usRNA), multispliced tat-rev RNA (tat-rev msRNA) and polyA mRNA.
  
  
  
  Significant increases in gag usRNA after influenza/hepatitis B vaccination (P = 0.02) and in gag usRNA (P = 0.04) and polyA mRNA (P = 0.04) after pneumococcus/hepatitis B vaccination were seen in vaccinees but not controls. HIV DNA and plasma HIV RNA did not change in either group. Increases in CD4 and CD8 T-cell activation markers (P = 0.08 and P < 0.001, respectively) and HIV-specific CD8 responses (P = 0.04 for p24 gag, P = 0.01 for p17 gag and P = 0.04 for total gag) were seen in vaccinees but not controls.
  
  
  
  In this study, vaccination was associated with increases in HIV cell-associated RNA and HIV-specific responses during antiretroviral therapy. Using standard vaccines to stimulate HIV transcription may therefore be a useful component of future eradication strategies.
authors.affiliation: aUniversity of California San Diego, La Jolla, California, USA bInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) cMedical Intensive Care Unit dDepartment of Infectious Diseases, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain eVeterans Affairs Healthcare System, San Diego, California, USA. *Present address: Christina Yek, University of Texas Southwestern Medical Center, Dallas, Texas, USA. †Present address: Konrad Scheffler, Illumina, San Diego, California, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Yek
authors.forename: Sara
authors.initials: S
authors.lastname: Gianella
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Pedro
authors.initials: P
authors.lastname: Castro
authors.forename: Konrad
authors.initials: K
authors.lastname: Scheffler
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D014158:Transcription, Genetic; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D044966:Anti-Retroviral Agents; D001428:Bacterial Vaccines; D010919:Placebos; D014765:Viral Vaccines