TY - JOUR
TI - Short Communication: CD4 T Cell Declines Occurring During Suppressive
Antiretroviral Therapy Reflect Continued Production of Casp8p41
AU - Cummins, Nathan W.
AU - Neuhaus, Jacqueline
AU - Sainski, Amy M. and
AU - Strausbauch, Michael A.
AU - Wettstein, Peter J.
AU - Lewin, Sharon R. and
AU - Plana, Montserrat
AU - Rizza, Stacey A.
AU - Temesgen, Zelalem and
AU - Touloumi, Giota
AU - Freiberg, Matthew
AU - Neaton, James
AU - Badley,
AU - Andrew D.
AU - INSIGHT SMART Study Grp
JO - AIDS Research and Human Retroviruses
PY - 2014
VL - 30
TODO - 5
SP - 476-479
PB - MARY ANN LIEBERT INC PUBL
SN - 0889-2229, 1931-8405
TODO - 10.1089/aid.2013.0243
TODO - null
TODO - Most patients on suppressive antiretroviral therapy (ART) experience
improvements in CD4 T cell count. However, some patients with
undetectable viral load continue to lose CD4 T cells for unknown
reasons. Casp8p41 is a host-derived protein fragment that is present
only in productively infected cells and that causes the death of
HIV-infected cells. We questioned whether ongoing CD4(+) T cell losses
while on suppressive ART were associated with subclinical HIV
replication causing production of Casp8p41. We analyzed the association
of Casp8p41 content with subsequent CD4 losses in patients on continuous
suppressive ART and in patients who discontinued ART after Casp8p41
content was determined, adjusting for age, baseline CD4(+) T cell count,
and baseline HIV RNA level. Casp8p41 expression in memory CD4(+) T cells
was measured by intracellular flow cytometry and was correlated with
viral load and CD4(+) T cell change over time. In patients who stopped
therapy after Casp8p41 content was determined, baseline Casp8p41 content
did not predict CD4(+) T cell change. However, in patients on continuous
ART, higher baseline Casp8p41 content was associated with a greater odds
of a CD4(+) T cell decline at 6 months (p=0.01). Therefore, patients on
suppressive ART, who have ongoing production of Casp8p41, have an
increased risk of CD4 T cell losses, suggesting that subclinical HIV
replication is driving both Casp8p41, which in turn causes a CD4(+) T
cell decline.
ER -