TY - JOUR
T1 - Short communication
T2 - 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.
AU - Strausbauch, Michael A.
AU - Wettstein, Peter J.
AU - Lewin, Sharon R.
AU - Plana, Montserrat
AU - Rizza, Stacey A.
AU - Temesgen, Zelalem
AU - Touloumi, Giota
AU - Freiberg, Matthew
AU - Neaton, James
AU - Badley, Andrew D.
PY - 2014/5/30
Y1 - 2014/5/30
N2 - 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.
AB - 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.
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U2 - 10.1089/aid.2013.0243
DO - 10.1089/aid.2013.0243
M3 - Article
C2 - 24344953
AN - SCOPUS:84899848259
SN - 0889-2229
VL - 30
SP - 476
EP - 479
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
IS - 5
ER -