Combination
antiretroviral therapy (ART) typically lowers HIV viral
load to an undetectable level within a few months of starting
treatment. Then -- with little or no new replicating virus
to infect them -- CD4 cells begin to recover, often reaching
near-normal levels.
But
some individuals -- especially those who start treatment later
with more advanced disease -- experience full viral suppression
without significant CD4 cell recovery, a phenomenon known
as discordant response.
HIV
experts do not yet full understand why discordant response
occurs or what are its clinical
consequences. But researchers in Austria recently identified
a marker that may help predict which patients will experience
poor immune recovery despite viral load suppression.
Katharina
Grabmeier-Pfistershammer from Medical University Vienna and
colleagues analyzed PD-1 expression on CD4 and CD8 T-cells
of HIV patients with poor immune recovery despite virologically
successful ART.
PD-1 expression on T-cells correlates with cell exhaustion
and disease progression in people with HIV, the study authors
noted as background. Previous research has shown that viral
suppression on ART usually results in immune restoration and
reduced PD-1 expression, but this does not always occur.
In this laboratory analysis, investigators looked at expression
of surface markers on T-cells from patients experiencing discordant
virological/immunological response.
Results
 |
T-cells
from people with discordant response expressed significantly
higher levels of PD-1 than those from people with normal
CD4 cell recovery after starting ART. |
|
PD-1
expression was inversely correlated with CD4 cell count. |
|
Poor
immune recovery was not, however, associated with increased
expression of markers of T-cell activation in general. |
|
T-cells
expressing PD-1 were more prone to inhibition of cell
proliferation mediated by programmed death ligand. |
The finding that discordant responders showed increased PD-1
expression but not increased T-cell activation overall suggests
that "PD-1 is a unique marker for failing immune reconstitution
despite viral suppression," the researchers wrote.
Furthermore, they found that T-cells from HIV patients with
poor immune recovery differed from those of elderly people,
again showing that stepped-up PD-1 expression is distinct
from the overall immune system exhaustion that comes with
age, known as immunosenescence.
In conclusion, the study authors wrote, these findings indicate
that "PD-1-mediated T-cell suppression may have a role
in impaired immune reconstitution in HIV patients."
Investigator affiliations: Department of Dermatology, Division
of Immunology, Allergy and Infectious Diseases, Medical University
Vienna, Vienna, Austria; Institute of Immunology, Center of
Physiology, Pathophysiology and Immunology, Medical University
Vienna, Vienna, Austria; aDepartment of Dermatology, Wilhelminenspital,
Vienna, Austria.
1/21/11
Reference
K
Grabmeier-Pfistershammer, P Steinberger, A Rieger, and others.
Identification of PD-1 as a Unique Marker for Failing Immune
Reconstitution in HIV-1-Infected Patients on Treatment. Journal
of Acquired Immune Deficiency Syndromes 56(2): 118-124
(Abstract).
February 1, 2011.
