Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection.
BACKGROUND
Rare human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell-mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown.


METHODS
We measured CD8+ T-cell-mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1-seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline.


RESULTS
There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4+ T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = -0.68 and P = .002).


CONCLUSIONS
The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation.
Oxford NIHR Biomedical Research Centre, United Kingdom.
Hongbing
H
Yang
Hao
H
Wu
Gemma
G
Hancock
Genevieve
G
Clutton
Nellia
N
Sande
Xiaoning
X
Xu
Huiping
H
Yan
Xiaojie
X
Huang
Brian
B
Angus
Kristin
K
Kuldanek
Sarah
S
Fidler
Thomas N
TN
Denny
Jacqueline
J
Birks
Andrew
A
McMichael
Lucy
L
Dorrell
D000328:Adult; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis
D015415:Biomarkers