title: Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir.
abstract: OBJECTIVE
  Therapeutic HIV vaccinations may alter the size of the resting memory CD4 T-cell latent HIV reservoir as HIV establishes latency when memory responses are formed, including those toward HIV. Alternatively, latently infected CD4 T cells maybe killed, while exiting the reservoir upon activation.
  
  
  METHODS
  The effect of therapeutic immunization with modified vaccinia Ankara and Fowlpox-based HIV vaccines on the latent reservoir was examined in 19 young adults who were receiving effective antiretroviral therapy. Correlations between size of the reservoir [measured in infectious units per million (IUPM)] resting CD4 T cells and HIV-specific immune responses, including immune activation were examined. Decay of the reservoir was assessed using random-effects model.
  
  
  RESULTS
  A modest transient decrease in the size of the reservoir was observed at week 40 [mean -0.31 log(10) IUPM (95% confidence interval: -0.60 to -0.03; P = 0.03] following HIV vaccinations. The estimated half-life (T1/2) of the reservoir during the 40 weeks following vaccination was 9.8 months and statistically different from zero (P = 0.02), but 35.3 months and not different from zero (P = 0.21) over 72 weeks of study. Latent reservoir size at baseline was not correlated with HIV-specific CD4, CD8 responses or immune activation, but became correlated with CD4 IFNγ (r = 0.54, P = 0.02) and IL-2 responses at 6 weeks after immunization (r = 0.48, P = 0.04).
  
  
  CONCLUSIONS
  Therapeutic HIV vaccinations led to a transient increase in decay of latently infected CD4 T cells. Further studies of therapeutic HIV vaccines may provide important insights into facilitating decay of the latent reservoir.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. dpers@jhmi.edu
authors.forename: Deborah
authors.initials: D
authors.lastname: Persaud
authors.forename: Katherine
authors.initials: K
authors.lastname: Luzuriaga
authors.forename: Carrie
authors.initials: C
authors.lastname: Ziemniak
authors.forename: Petronella
authors.initials: P
authors.lastname: Muresan
authors.forename: Thomas
authors.initials: T
authors.lastname: Greenough
authors.forename: Terry
authors.initials: T
authors.lastname: Fenton
authors.forename: Amanda
authors.initials: A
authors.lastname: Blackford
authors.forename: Kimberly
authors.initials: K
authors.lastname: Ferguson
authors.forename: Natalie
authors.initials: N
authors.lastname: Neu
authors.forename: Coleen K
authors.initials: CK
authors.lastname: Cunningham
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016896:Treatment Outcome; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D014614:Vaccines, Synthetic