692
CD8+ T-cell Activation in Pediatric HIV
Norma Pérez*, G Del Bianco, G Heresi, and J Murphy
Univ of Texas Med Sch, Houston, US
Background: Clinical trials demonstrate that measurements
of CD38 and DR on CD8+ cells can distinguish patients with better or
worse HIV infection status and may provide an additional or better level of
discrimination to measurements of CD4 and viral load. In the setting of a
pediatric HIV clinic providing routine care, we evaluated CD8 T cells for CD38,
DR, or CD38+DR expression to determine if these markers associated
with outcomes that might aid in patient management.
Methods: This is an ongoing prospective pediatric
cohort study of 14 months duration.
Results: Patients were stratified by ART status (table
1). Percentage of CD8+CD38+
cells was lowest for patients with the best HIV disease status, but independent
of viral load or CD4 or CD8 percentage. Notably, patients who maintained good
CD4 percentage and reasonable control of viral load in the absence of ART had
high rates of CD8+CD38+ cells. To determine changes over
the period of observation, paired first and last measurements for all outcomes
within each of the ART groups were compared (table 2). All ART groups were
stable on all outcomes over the observation period except the NC→C group,
in which viral load and all measured markers of CD8+ cell activation
declined significantly over the study. Activation markers demonstrated marked
improvement where neither CD4 nor CD8 percentage change reached significance.
Conclusions: Measurements of activation markers on CD8+
cells in a pediatric HIV clinic providing routine care, discriminated groups
with differing clinical status with respect to HIV disease. In NC→C
patients, clinical improvement paralleled decline of all activation markers and
activation was a marker of ART compliance. In contrast, ART-naive individuals
with reasonable control of viral load (average <8000 RNA copies/mL) and good
CD4 percentage (35%) had markedly elevated levels of CD8+
activation. If reduced CD8+ activation is accepted as a clinical
goal, management of these should be changed.
|
Table 1
|
ART Status
|
|
|
Naive
|
Off
|
Compliant
|
Non-compliant
|
NC→C
|
|
Number
|
6 (21)
|
7 (27)
|
17 (63)
|
9 (34)
|
10 (47)
|
|
log RNA
copies/mL
|
3.86
|
4.25
|
2.74
|
3.26
|
4.22
|
|
CD4%
|
34.59
|
34.56
|
33.58
|
22.83
|
23.33
|
|
CD8%
|
37.09
|
43.03
|
33.22
|
43.37
|
46.42
|
|
CD8+CD38+%
|
55.61
|
49.22
|
44.88
|
46.51
|
58.46
|
|
CD8+DR+%
|
17.28
|
17.01
|
11.02
|
6.58
|
13.65
|
|
CD8+CD38+DR+%
|
12.22
|
10.58
|
7.39
|
4.52
|
9.28
|
NC→C = non-compliant to compliant. Number = patients (observations). Significant
differences are boldface;
ANOVA or t-test.
|
Table 2
|
Determination
|
|
Outcome
|
First
|
Last
|
|
log RNA
copies/mL
|
4.25
|
2.71
|
|
CD4%
|
17.7
|
26.7
|
|
CD8%
|
48.6
|
39.8
|
|
CD8+CD38+%
|
72.2
|
22.5
|
|
CD8+DR+%
|
7.8
|
2.3
|
|
CD8+CD38+DR+%
|
6.3
|
1.2
|
|
