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

doi:10.1097/QAD.0000000000001480

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Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals

Journal article

Peer reviewed

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 and Ashwin Balagopal

AIDS (London), Vol.31(10), pp.1405-1414

06/19/2017

DOI: 10.1097/QAD.0000000000001480

PMCID: PMC5572749

PMID: 28358734

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Abstract

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). Clinical trial (NCT01285050). Next-generation sequencing was used to study total RNA from activated CD4 T cells (CD38 and human leukocyte antigen - antigen D related (HLA-DR) expressing) collected from 19 treatment-naïve HIV-1/hepatitis C virus-infected patients before and early after ART initiation (≥12 weeks after plasma HIV-1 RNA <50 copies/ml). To validate comparisons, pre and post-ART measures were adjusted for input RNA and overall read number. As expected, ART use was associated with a median [interquartile range (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 with 72 (55-152) HIV-1 reads/10 reads after at least 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). Months of ART led to a marked decrease in cell-associated HIV-1 RNA and interferon-stimulated genes expression in activated CD4 T cells that were strongly associated with the reduction in the proportion of activated CD4 T cells.

Adult

Anti-Retroviral Agents - therapeutic use

CD4-Positive T-Lymphocytes - immunology

CD4-Positive T-Lymphocytes - virology

Female

High-Throughput Nucleotide Sequencing

HIV Infections - drug therapy

HIV Infections - immunology

HIV Infections - virology

HIV-1 - genetics

HIV-1 - immunology

Humans

Lymphocyte Activation

Male

Middle Aged

Prospective Studies

RNA, Viral - analysis

Young Adult

Details

Title: Subtitle: Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals
Creators: Ramy El-Diwany - Johns Hopkins University School of Medicine
Florian P Breitwieser
Mary Soliman
Alyza M Skaist
Geetha Srikrishna
Joel N Blankson
Stuart C Ray
Sarah J Wheelan
David L Thomas
Ashwin Balagopal
Resource Type: Journal article
Publication Details: AIDS (London), Vol.31(10), pp.1405-1414
DOI: 10.1097/QAD.0000000000001480
PMID: 28358734
PMCID: PMC5572749
NLM abbreviation: AIDS
ISSN: 0269-9370
eISSN: 1473-5571
Grant note: P30 CA006973 / NCI NIH HHS R01 DA016078 / NIDA NIH HHS UL1 TR000424 / NCATS NIH HHS T32 GM008752 / NIGMS NIH HHS UM1 AI068613 / NIAID NIH HHS R37 DA013806 / NIDA NIH HHS P30 AI094189 / NIAID NIH HHS R01 DA013806 / NIDA NIH HHS T32 GM007309 / NIGMS NIH HHS
Language: English
Date published: 06/19/2017
Academic Unit: Surgery
Record Identifier: 9984966749502771

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