title: CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.
abstract: HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population.
  
  
  
  We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.
  
  
  
  12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.
  
  
  
  HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.|Department of Medicine, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Avelino-Silva
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Karina T
authors.initials: KT
authors.lastname: Miyaji
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, School of Pharmacy, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Marisol
authors.initials: M
authors.lastname: Simoes
authors.affiliation: Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Sheila B
authors.initials: SB
authors.lastname: Lima
authors.affiliation: Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Marcos S
authors.initials: MS
authors.lastname: Freire
authors.affiliation: Instituto Adolfo Lutz, São Paulo, Brazil.|Laboratory of Medical Investigation LIM-3, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Helio H
authors.initials: HH
authors.lastname: Caiaffa-Filho
authors.affiliation: Instituto Adolfo Lutz, São Paulo, Brazil.|Division of Clinical Immunology and Allergy, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Marisa A
authors.initials: MA
authors.lastname: Hong
authors.affiliation: Division of Clinical Immunology and Allergy, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Dayane Alves
authors.initials: DA
authors.lastname: Costa
authors.affiliation: Division of Clinical Immunology and Allergy, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Juliana Zanatta C
authors.initials: JZ
authors.lastname: Dias
authors.affiliation: Division of Clinical Immunology and Allergy, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Natalia B
authors.initials: NB
authors.lastname: Cerqueira
authors.affiliation: Fundação Pro-Sangue Hemocentro de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Anna Shoko
authors.initials: AS
authors.lastname: Nishiya
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.|Fundação Pro-Sangue Hemocentro de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ester Cerdeira
authors.initials: EC
authors.lastname: Sabino
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sartori
authors.affiliation: Department of Infectious and Parasitic Diseases, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.|Division of Clinical Immunology and Allergy, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D016516:CD4-CD8 Ratio; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D000071497:Immunogenicity, Vaccine; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007737:Kynurenine / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014364:Tryptophan / Q000097:blood*; D014766:Viremia; D015004:Yellow Fever / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022341:Yellow Fever Vaccine / Q000009:adverse effects / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D022341:Yellow Fever Vaccine; D007737:Kynurenine; D014364:Tryptophan