title: A high viral burden predicts the loss of CD8 T-cell responses specific for subdominant gag epitopes during chronic human immunodeficiency virus infection.
abstract: Human immunodeficiency virus (HIV)-specific CD8 T-cell responses targeting products encoded within the Gag open reading frame have frequently been associated with better viral control and disease outcome during the chronic phase of HIV infection. To further clarify this relationship, we have studied the dynamics of Gag-specific CD8 T-cell responses in relation to plasma viral load and time since infection in 33 chronically infected subjects over a 9-month period. High baseline viral loads were associated with a net loss of breadth (P < 0.001) and a decrease in the total magnitude of the Gag-specific T-cell response in general (P = 0.03). Most importantly, the baseline viral load predicted the subsequent change in the breadth of Gag recognition over time (P < 0.0001, r(2) = 0.41). Compared to maintained responses, lost responses were low in magnitude (P < 0.0001) and subdominant in the hierarchy of Gag-specific responses. The present study indicates that chronic exposure of the human immune system to high levels of HIV viremia is a determinant of virus-specific CD8 T-cell loss.
authors: Mbeya Medical Research Programme, Referral Hospital, Mbeya, Tanzania. geldmacherc@mail.nih.gov
authors: Christof
authors: C
authors: Geldmacher
authors: Clive
authors: C
authors: Gray
authors: Martha
authors: M
authors: Nason
authors: Jeffrey R
authors: JR
authors: Currier
authors: Antelmo
authors: A
authors: Haule
authors: Lilian
authors: L
authors: Njovu
authors: Steffen
authors: S
authors: Geis
authors: Oliver
authors: O
authors: Hoffmann
authors: Leonard
authors: L
authors: Maboko
authors: Andreas
authors: A
authors: Meyerhans
authors: Josephine
authors: J
authors: Cox
authors: Michael
authors: M
authors: Hoelscher
mesh_terms: D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D015331:Cohort Studies; D000939:Epitopes / Q000737:chemistry; D005260:Female; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014766:Viremia
chemical_list: D000939:Epitopes; D015683:Gene Products, gag; D012367:RNA, Viral