Intracellular HIV-1 rna and CD4+ t cell activation in patients starting antiretrovirals

Ramy El-Diwany, Florian P. Breitwieser, Mary Soliman, Alyza M. Skaist, Geetha Srikrishna, Joel N. Blankson, Stuart C. Ray, Sarah J. Wheelan, David L. Thomas, Ashwin Balagopal

Research output: Contribution to journalArticle

Abstract

OBJECTIVE:: To assess if the reduction in HIV-1 RNA in CD4+ T cells is correlated with the persistence of immune activation following early antiretroviral therapy (ART). DESIGN:: Clinical trial (NCT01285050). METHODS:: Next-generation sequencing was used to study total RNA from activated CD4+ T cells (CD38 and HLA-DR expressing) collected from 19 treatment-naïve HIV-1/HCV infected patients before and early after ART initiation (≥12 weeks after plasma HIV RNA < 50?c/ml). To validate comparisons, pre- and post-ART measures were adjusted for input RNA and overall read number. RESULTS:: As expected, ART use was associated with a median (IQR) 4.3 (2.2–8.3) reduction in the proportion of activated CD4+ T cells (P?=?0.0008). Whereas in those activated CD4+ T cells no consistent differences in overall gene expression were detected, interferon stimulated gene expression declined (P?<?2?×?10). Pre-ART, sorted activated CD4+ T cells contained a median (IQR) of 959 (252–1614) HIV-1?reads/10 reads compared to 72 (55–152) HIV-1?reads/10 reads after ≥12 weeks of suppressive ART (P?=?8?×?10). The decrease in HIV-1 reads in activated CD4+ T cells was associated with the change in plasma HIV-1 RNA levels (r?=?0.77, P?=?2?×?10) and the change in the proportion of activated CD4+ T cells (r?=?0.70, P?=?0.0016). CONCLUSIONS:: Months of ART led to a marked decrease in cell-associated HIV-1 RNA and ISG expression in activated CD4+ T cells that were strongly associated with the reduction in the proportion of activated CD4+ T cells.

Original languageEnglish (US)
JournalAIDS
DOIs
StateAccepted/In press - Mar 29 2017

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HIV-1
T-Lymphocytes
RNA
Gene Expression
HLA-DR Antigens
Secondary Prevention
Interferons
Clinical Trials
HIV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Intracellular HIV-1 rna and CD4+ t cell activation in patients starting antiretrovirals. / El-Diwany, Ramy; Breitwieser, Florian P.; Soliman, Mary; Skaist, Alyza M.; Srikrishna, Geetha; Blankson, Joel N.; Ray, Stuart C.; Wheelan, Sarah J.; Thomas, David L.; Balagopal, Ashwin.

In: AIDS, 29.03.2017.

Research output: Contribution to journalArticle

El-Diwany R, Breitwieser FP, Soliman M, Skaist AM, Srikrishna G, Blankson JN et al. Intracellular HIV-1 rna and CD4+ t cell activation in patients starting antiretrovirals. AIDS. 2017 Mar 29. Available from, DOI: 10.1097/QAD.0000000000001480

El-Diwany, Ramy; Breitwieser, Florian P.; Soliman, Mary; Skaist, Alyza M.; Srikrishna, Geetha; Blankson, Joel N.; Ray, Stuart C.; Wheelan, Sarah J.; Thomas, David L.; Balagopal, Ashwin / Intracellular HIV-1 rna and CD4+ t cell activation in patients starting antiretrovirals.

In: AIDS, 29.03.2017.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVE:: To assess if the reduction in HIV-1 RNA in CD4+ T cells is correlated with the persistence of immune activation following early antiretroviral therapy (ART). DESIGN:: Clinical trial (NCT01285050). METHODS:: Next-generation sequencing was used to study total RNA from activated CD4+ T cells (CD38 and HLA-DR expressing) collected from 19 treatment-naïve HIV-1/HCV infected patients before and early after ART initiation (≥12 weeks after plasma HIV RNA < 50?c/ml). To validate comparisons, pre- and post-ART measures were adjusted for input RNA and overall read number. RESULTS:: As expected, ART use was associated with a median (IQR) 4.3 (2.2–8.3) reduction in the proportion of activated CD4+ T cells (P?=?0.0008). Whereas in those activated CD4+ T cells no consistent differences in overall gene expression were detected, interferon stimulated gene expression declined (P?<?2?×?10). Pre-ART, sorted activated CD4+ T cells contained a median (IQR) of 959 (252–1614) HIV-1?reads/10 reads compared to 72 (55–152) HIV-1?reads/10 reads after ≥12 weeks of suppressive ART (P?=?8?×?10). The decrease in HIV-1 reads in activated CD4+ T cells was associated with the change in plasma HIV-1 RNA levels (r?=?0.77, P?=?2?×?10) and the change in the proportion of activated CD4+ T cells (r?=?0.70, P?=?0.0016). CONCLUSIONS:: Months of ART led to a marked decrease in cell-associated HIV-1 RNA and ISG expression in activated CD4+ T cells that were strongly associated with the reduction in the proportion of activated CD4+ T cells.",
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AU - El-Diwany,Ramy

AU - Breitwieser,Florian P.

AU - Soliman,Mary

AU - Skaist,Alyza M.

AU - Srikrishna,Geetha

AU - Blankson,Joel N.

AU - Ray,Stuart C.

AU - Wheelan,Sarah J.

AU - Thomas,David L.

AU - Balagopal,Ashwin

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N2 - OBJECTIVE:: To assess if the reduction in HIV-1 RNA in CD4+ T cells is correlated with the persistence of immune activation following early antiretroviral therapy (ART). DESIGN:: Clinical trial (NCT01285050). METHODS:: Next-generation sequencing was used to study total RNA from activated CD4+ T cells (CD38 and HLA-DR expressing) collected from 19 treatment-naïve HIV-1/HCV infected patients before and early after ART initiation (≥12 weeks after plasma HIV RNA < 50?c/ml). To validate comparisons, pre- and post-ART measures were adjusted for input RNA and overall read number. RESULTS:: As expected, ART use was associated with a median (IQR) 4.3 (2.2–8.3) reduction in the proportion of activated CD4+ T cells (P?=?0.0008). Whereas in those activated CD4+ T cells no consistent differences in overall gene expression were detected, interferon stimulated gene expression declined (P?<?2?×?10). Pre-ART, sorted activated CD4+ T cells contained a median (IQR) of 959 (252–1614) HIV-1?reads/10 reads compared to 72 (55–152) HIV-1?reads/10 reads after ≥12 weeks of suppressive ART (P?=?8?×?10). The decrease in HIV-1 reads in activated CD4+ T cells was associated with the change in plasma HIV-1 RNA levels (r?=?0.77, P?=?2?×?10) and the change in the proportion of activated CD4+ T cells (r?=?0.70, P?=?0.0016). CONCLUSIONS:: Months of ART led to a marked decrease in cell-associated HIV-1 RNA and ISG expression in activated CD4+ T cells that were strongly associated with the reduction in the proportion of activated CD4+ T cells.

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