title: Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection.
abstract: BACKGROUND
  The challenges of identifying acute HIV infection (AHI) have resulted in a lack of critical information on early AHI that constrains the development of therapeutics that are designed to eradicate HIV from the infected host.
  
  
  METHODS
  AHI participants were recruited from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand into the RV254/SEARCH010 protocol and categorised according to Fiebig stages as follows: Fiebig I (HIV-RNA+, p24 Ag-, HIV IgM-) and Fiebig II-IV (HIV-RNA+, p24 Ag + or -, HIV IgM- or +, Western blot- or indeterminate). Proviral and viral burden and immune activation levels were compared between Fiebig stage groups at the time of AHI. CD4 and CD4/CD8 ratio were also compared between groups before and up to 96 weeks of ART.
  
  
  RESULTS
  Median age was 27 years and 96% were male. Fiebig I individuals had lower median HIV-DNA in mononuclear cells from blood (3vs. 190 copies/106cells) and gut (0vs. 898 copies/106cells), and lower HIV-RNA in blood (4.2vs. 6.2 log10copies/mL), gut (1.7vs. 3.1 log10copies/mg) and cerebrospinal fluid (2.0vs. 3.8 log10copies/mL), when compared to Fiebig II-IV individuals (allP<0.01). Median plasma sCD14 level was lower (1.1vs. 1.6 μg/mL) in Fiebig I individuals as was the frequency of CD8+HLADR+CD38+ T cells in blood (7.6vs. 14.9%, bothP<0.05). The median plasma interleukin 6 levels were similar between stages (0.6 in Fiebig Ivs. 0.5 pg/mL in Fiebig II-IV,P>0.05). The frequencies of CD4+HLA-DR+CD38+ T cells were also similar between these stages (2.1vs. 2.6%,P>0.05). Median CD4 count and CD4/CD8 ratio were higher in Fiebig I: 508vs. 340 cells/mm3and 1.1vs. 0.7, respectively (bothP<0.001). After ART, CD4 cell count normalised by week 24 in Fiebig I and week 48 in Fiebig II-IV. However, CD4/CD8 ratio was lower in both groups after 96 weeks of ART compared to healthy Thais (P=0.02).
  
  
  CONCLUSIONS
  Compared to later AHI stages, Fiebig I was associated with lower HIV burden in blood and tissue compartments, lower immune activation and higher CD4 and CD4/CD8 ratio. ART in Fiebig I-IV resulted in normalisation of CD4 cell count within the first year, supporting the benefit of early ART. However, the CD4/CD8 ratio was not normalised after 2 years of ART in all AHI stages, suggesting some degree of persistent immunological dysfunction even when ART was instituted as early as Fiebig I.
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Carlo P
authors.initials: CP
authors.lastname: Sacdalan
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Suteeraporn
authors.initials: S
authors.lastname: Pinyakorn
authors.affiliation: Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Faculty of Medicine, and Centre de Recherche du CHUM, Montreal, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Mark
authors.initials: M
authors.lastname: de Souza
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Tassanee
authors.initials: T
authors.lastname: Luekasemsuk
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Armed Forces Research Institute of Medical Sciences, US Component, Bangkok, Thailand.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Shelly J
authors.initials: SJ
authors.lastname: Krebs
authors.affiliation: Leidos Biomedical Research Inc, Virus Isolation and Serology Laboratory, Frederick, MD, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Dewar
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Jagodzinski
authors.affiliation: HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Sasiwimol
authors.initials: S
authors.lastname: Ubolyam
authors.affiliation: Armed Forces Research Institute of Medical Sciences, US Component, Bangkok, Thailand.
authors.forename: Rapee
authors.initials: R
authors.lastname: Trichavaroj
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Sodsai
authors.initials: S
authors.lastname: Tovanabutra
authors.affiliation: Department of Neurology, Yale University, New Haven, CT, USA.
authors.forename: Serena
authors.initials: S
authors.lastname: Spudich
authors.affiliation: Department of Neurology, University of California, San Francisco, CA, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Michael
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Merlin
authors.initials: M
authors.lastname: Robb
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.affiliation: United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
keywords: CD4; CD4/CD8 ratio; Fiebig I; acute HIV infection; immune activation; reservoir