Short Communication: CD4 T Cell Declines Occurring During Suppressive Antiretroviral Therapy Reflect Continued Production of Casp8p41

Abstract 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 C...