Short communication: CD4 T cell declines occurring during suppressive antiretroviral therapy reflect continued production of Casp8p41

Nathan W Cummins, Jacqueline Neuhaus, Amy M Sainski, Michael A Strausbauch, Peter J Wettstein, Sharon Ruth Lewin, Montserrat Plana, Stacey A Rizza, Zelalem Temesgen, Giota Touloumi, Matthew S Freiberg, James D Neaton, Andrew D Badley

Research output: Contribution to journalArticleOtherpeer-review

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Abstract

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 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.
Original languageEnglish
Pages (from-to)476 - 479
Number of pages4
JournalAIDS Research and Human Retroviruses
Volume30
Issue number5
DOIs
Publication statusPublished - 2014

Cite this

Cummins, Nathan W ; Neuhaus, Jacqueline ; Sainski, Amy M ; Strausbauch, Michael A ; Wettstein, Peter J ; Lewin, Sharon Ruth ; Plana, Montserrat ; Rizza, Stacey A ; Temesgen, Zelalem ; Touloumi, Giota ; Freiberg, Matthew S ; Neaton, James D ; Badley, Andrew D. / Short communication: CD4 T cell declines occurring during suppressive antiretroviral therapy reflect continued production of Casp8p41. In: AIDS Research and Human Retroviruses. 2014 ; Vol. 30, No. 5. pp. 476 - 479.
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title = "Short communication: CD4 T cell declines occurring during suppressive antiretroviral therapy reflect continued production of Casp8p41",
abstract = "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 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.",
author = "Cummins, {Nathan W} and Jacqueline Neuhaus and Sainski, {Amy M} and Strausbauch, {Michael A} and Wettstein, {Peter J} and Lewin, {Sharon Ruth} and Montserrat Plana and Rizza, {Stacey A} and Zelalem Temesgen and Giota Touloumi and Freiberg, {Matthew S} and Neaton, {James D} and Badley, {Andrew D}",
year = "2014",
doi = "10.1089/aid.2013.0243",
language = "English",
volume = "30",
pages = "476 -- 479",
journal = "AIDS Research and Human Retroviruses",
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Cummins, NW, Neuhaus, J, Sainski, AM, Strausbauch, MA, Wettstein, PJ, Lewin, SR, Plana, M, Rizza, SA, Temesgen, Z, Touloumi, G, Freiberg, MS, Neaton, JD & Badley, AD 2014, 'Short communication: CD4 T cell declines occurring during suppressive antiretroviral therapy reflect continued production of Casp8p41', AIDS Research and Human Retroviruses, vol. 30, no. 5, pp. 476 - 479. https://doi.org/10.1089/aid.2013.0243

Short communication: CD4 T cell declines occurring during suppressive antiretroviral therapy reflect continued production of Casp8p41. / Cummins, Nathan W; Neuhaus, Jacqueline; Sainski, Amy M; Strausbauch, Michael A; Wettstein, Peter J; Lewin, Sharon Ruth; Plana, Montserrat; Rizza, Stacey A; Temesgen, Zelalem; Touloumi, Giota; Freiberg, Matthew S; Neaton, James D; Badley, Andrew D.

In: AIDS Research and Human Retroviruses, Vol. 30, No. 5, 2014, p. 476 - 479.

Research output: Contribution to journalArticleOtherpeer-review

TY - JOUR

T1 - 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

AU - Strausbauch, Michael A

AU - Wettstein, Peter J

AU - Lewin, Sharon Ruth

AU - Plana, Montserrat

AU - Rizza, Stacey A

AU - Temesgen, Zelalem

AU - Touloumi, Giota

AU - Freiberg, Matthew S

AU - Neaton, James D

AU - Badley, Andrew D

PY - 2014

Y1 - 2014

N2 - 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 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 - 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 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

VL - 30

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EP - 479

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

SN - 0889-2229

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