Acute Retroviral Syndrome Is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments

Trevor A. Crowell; Donn J. Colby; Suteeraporn Pinyakorn; James L.K. Fletcher; Eugène Kroon; Alexandra Schuetz; Shelly J. Krebs; Bonnie M. Slike; Louise Leyre; Nicolas Chomont; Linda L. Jagodzinski; Irini Sereti; Netanya S. Utay; Robin Dewar; Rungsun Rerknimitr; Nitiya Chomchey; Rapee Trichavaroj; Victor G. Valcour; Serena Spudich; Nelson L. Michael; Merlin L. Robb; Nittaya Phanuphak; Jintanat Ananworanich; Nipat Teeratakulpisarn; Carlo Sacdalan; Duanghathai Sutthichom; Somprartthana Rattanamanee; Peeriya Prueksakaew; Sasiwimol Ubolyam; Pacharin Eamyoung; Suwanna Puttamaswin; Somporn Tipsuk; Putthachard Karnsomlap; Wiriyaporn Ridtitid; Robert J. O'Connell; Siriwat Akapirat; Yuwadee Phuang-Ngern; Suchada Sukhumvittaya; Chayada Sajjaweerawan; Surat Jongrakthaitae; Putita Saetun; Nipattra Tragonlugsana; Bessara Nuntapinit; Nantana Tantibul; Hathairat Savadsuk; Sodsai Tovanabutr

doi:10.1093/cid/cix1063

Acute Retroviral Syndrome Is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments

Trevor A. Crowell^*, Donn J. Colby, Suteeraporn Pinyakorn, James L.K. Fletcher, Eugène Kroon, Alexandra Schuetz, Shelly J. Krebs, Bonnie M. Slike, Louise Leyre, Nicolas Chomont, Linda L. Jagodzinski, Irini Sereti, Netanya S. Utay, Robin Dewar, Rungsun Rerknimitr, Nitiya Chomchey, Rapee Trichavaroj, Victor G. Valcour, Serena Spudich, Nelson L. MichaelMerlin L. Robb, Nittaya Phanuphak, Jintanat Ananworanich, Nipat Teeratakulpisarn, Carlo Sacdalan, Duanghathai Sutthichom, Somprartthana Rattanamanee, Peeriya Prueksakaew, Sasiwimol Ubolyam, Pacharin Eamyoung, Suwanna Puttamaswin, Somporn Tipsuk, Putthachard Karnsomlap, Wiriyaporn Ridtitid, Robert J. O'Connell, Siriwat Akapirat, Yuwadee Phuang-Ngern, Suchada Sukhumvittaya, Chayada Sajjaweerawan, Surat Jongrakthaitae, Putita Saetun, Nipattra Tragonlugsana, Bessara Nuntapinit, Nantana Tantibul, Hathairat Savadsuk, Sodsai Tovanabutr

^*Corresponding author for this work

Infectious Disease Clinical Research Program (IDCRP)

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

Background Many individuals with acute human immunodeficiency virus infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes. Methods Participants presenting for voluntary human immunodeficiency virus (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers were stratified by ARS diagnosis at enrollment and after up to 96 weeks of antiretroviral therapy (ART). Results From 212382 samples screened, 430 participants were enrolled during AHI, including 335 (78%) with ARS. Median age was 26 years and 416 (97%) were men. Sixty (14%) underwent sigmoid biopsy and 105 (24%) underwent lumbar puncture during AHI. Common symptoms included fever (93%), fatigue (79%), pharyngitis (67%), and headache (64%). Compared to those without ARS, participants with ARS were in later Fiebig stages with higher HIV RNA in blood, colon, and cerebrospinal fluid; higher total HIV DNA in blood; CD4 depletion in blood and colon; and elevated plasma tumor necrosis factor alpha (TNF-α), C-reactive protein, and D-dimer (all P <.05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNF-α and interleukin 6 were elevated in the ARS group (P <.05) but other biomarkers equilibrated. Conclusions ARS was associated with high viral burden, CD4 depletion, and immune activation across multiple body compartments during AHI and prior to ART. Persistent inflammation despite suppressive ART could contribute to increased morbidity in individuals who experience ARS.

Original language	English
Pages (from-to)	1540-1549
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	66
Issue number	10
DOIs	https://doi.org/10.1093/cid/cix1063
State	Published - 2 May 2018

Keywords

CD4 lymphocyte count
HIV
acute retroviral syndrome
highly active antiretroviral therapy
inflammation

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10.1093/cid/cix1063

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Crowell, T. A., Colby, D. J., Pinyakorn, S., Fletcher, J. L. K., Kroon, E., Schuetz, A., Krebs, S. J., Slike, B. M., Leyre, L., Chomont, N., Jagodzinski, L. L., Sereti, I., Utay, N. S., Dewar, R., Rerknimitr, R., Chomchey, N., Trichavaroj, R., Valcour, V. G., Spudich, S., ... Tovanabutr, S. (2018). Acute Retroviral Syndrome Is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments. Clinical Infectious Diseases, 66(10), 1540-1549. https://doi.org/10.1093/cid/cix1063

@article{fc6a2466ba5049509ff60dd59332dd83,

title = "Acute Retroviral Syndrome Is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments",

abstract = "Background Many individuals with acute human immunodeficiency virus infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes. Methods Participants presenting for voluntary human immunodeficiency virus (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers were stratified by ARS diagnosis at enrollment and after up to 96 weeks of antiretroviral therapy (ART). Results From 212382 samples screened, 430 participants were enrolled during AHI, including 335 (78%) with ARS. Median age was 26 years and 416 (97%) were men. Sixty (14%) underwent sigmoid biopsy and 105 (24%) underwent lumbar puncture during AHI. Common symptoms included fever (93%), fatigue (79%), pharyngitis (67%), and headache (64%). Compared to those without ARS, participants with ARS were in later Fiebig stages with higher HIV RNA in blood, colon, and cerebrospinal fluid; higher total HIV DNA in blood; CD4 depletion in blood and colon; and elevated plasma tumor necrosis factor alpha (TNF-α), C-reactive protein, and D-dimer (all P <.05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNF-α and interleukin 6 were elevated in the ARS group (P <.05) but other biomarkers equilibrated. Conclusions ARS was associated with high viral burden, CD4 depletion, and immune activation across multiple body compartments during AHI and prior to ART. Persistent inflammation despite suppressive ART could contribute to increased morbidity in individuals who experience ARS.",

keywords = "CD4 lymphocyte count, HIV, acute retroviral syndrome, highly active antiretroviral therapy, inflammation",

author = "Crowell, {Trevor A.} and Colby, {Donn J.} and Suteeraporn Pinyakorn and Fletcher, {James L.K.} and Eug{\`e}ne Kroon and Alexandra Schuetz and Krebs, {Shelly J.} and Slike, {Bonnie M.} and Louise Leyre and Nicolas Chomont and Jagodzinski, {Linda L.} and Irini Sereti and Utay, {Netanya S.} and Robin Dewar and Rungsun Rerknimitr and Nitiya Chomchey and Rapee Trichavaroj and Valcour, {Victor G.} and Serena Spudich and Michael, {Nelson L.} and Robb, {Merlin L.} and Nittaya Phanuphak and Jintanat Ananworanich and Nipat Teeratakulpisarn and Carlo Sacdalan and Duanghathai Sutthichom and Somprartthana Rattanamanee and Peeriya Prueksakaew and Sasiwimol Ubolyam and Pacharin Eamyoung and Suwanna Puttamaswin and Somporn Tipsuk and Putthachard Karnsomlap and Wiriyaporn Ridtitid and O'Connell, {Robert J.} and Siriwat Akapirat and Yuwadee Phuang-Ngern and Suchada Sukhumvittaya and Chayada Sajjaweerawan and Surat Jongrakthaitae and Putita Saetun and Nipattra Tragonlugsana and Bessara Nuntapinit and Nantana Tantibul and Hathairat Savadsuk and Sodsai Tovanabutr",

note = "Publisher Copyright: {\textcopyright}.",

year = "2018",

month = may,

day = "2",

doi = "10.1093/cid/cix1063",

language = "English",

volume = "66",

pages = "1540--1549",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "10",

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Crowell, TA, Colby, DJ, Pinyakorn, S, Fletcher, JLK, Kroon, E, Schuetz, A, Krebs, SJ, Slike, BM, Leyre, L, Chomont, N, Jagodzinski, LL, Sereti, I, Utay, NS, Dewar, R, Rerknimitr, R, Chomchey, N, Trichavaroj, R, Valcour, VG, Spudich, S, Michael, NL, Robb, ML, Phanuphak, N, Ananworanich, J, Teeratakulpisarn, N, Sacdalan, C, Sutthichom, D, Rattanamanee, S, Prueksakaew, P, Ubolyam, S, Eamyoung, P, Puttamaswin, S, Tipsuk, S, Karnsomlap, P, Ridtitid, W, O'Connell, RJ, Akapirat, S, Phuang-Ngern, Y, Sukhumvittaya, S, Sajjaweerawan, C, Jongrakthaitae, S, Saetun, P, Tragonlugsana, N, Nuntapinit, B, Tantibul, N, Savadsuk, H & Tovanabutr, S 2018, 'Acute Retroviral Syndrome Is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments', Clinical Infectious Diseases, vol. 66, no. 10, pp. 1540-1549. https://doi.org/10.1093/cid/cix1063

TY - JOUR

T1 - Acute Retroviral Syndrome Is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments

AU - Crowell, Trevor A.

AU - Colby, Donn J.

AU - Pinyakorn, Suteeraporn

AU - Fletcher, James L.K.

AU - Kroon, Eugène

AU - Schuetz, Alexandra

AU - Krebs, Shelly J.

AU - Slike, Bonnie M.

AU - Leyre, Louise

AU - Chomont, Nicolas

AU - Jagodzinski, Linda L.

AU - Sereti, Irini

AU - Utay, Netanya S.

AU - Dewar, Robin

AU - Rerknimitr, Rungsun

AU - Chomchey, Nitiya

AU - Trichavaroj, Rapee

AU - Valcour, Victor G.

AU - Spudich, Serena

AU - Michael, Nelson L.

AU - Robb, Merlin L.

AU - Phanuphak, Nittaya

AU - Ananworanich, Jintanat

AU - Teeratakulpisarn, Nipat

AU - Sacdalan, Carlo

AU - Sutthichom, Duanghathai

AU - Rattanamanee, Somprartthana

AU - Prueksakaew, Peeriya

AU - Ubolyam, Sasiwimol

AU - Eamyoung, Pacharin

AU - Puttamaswin, Suwanna

AU - Tipsuk, Somporn

AU - Karnsomlap, Putthachard

AU - Ridtitid, Wiriyaporn

AU - O'Connell, Robert J.

AU - Akapirat, Siriwat

AU - Phuang-Ngern, Yuwadee

AU - Sukhumvittaya, Suchada

AU - Sajjaweerawan, Chayada

AU - Jongrakthaitae, Surat

AU - Saetun, Putita

AU - Tragonlugsana, Nipattra

AU - Nuntapinit, Bessara

AU - Tantibul, Nantana

AU - Savadsuk, Hathairat

AU - Tovanabutr, Sodsai

PY - 2018/5/2

Y1 - 2018/5/2

N2 - Background Many individuals with acute human immunodeficiency virus infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes. Methods Participants presenting for voluntary human immunodeficiency virus (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers were stratified by ARS diagnosis at enrollment and after up to 96 weeks of antiretroviral therapy (ART). Results From 212382 samples screened, 430 participants were enrolled during AHI, including 335 (78%) with ARS. Median age was 26 years and 416 (97%) were men. Sixty (14%) underwent sigmoid biopsy and 105 (24%) underwent lumbar puncture during AHI. Common symptoms included fever (93%), fatigue (79%), pharyngitis (67%), and headache (64%). Compared to those without ARS, participants with ARS were in later Fiebig stages with higher HIV RNA in blood, colon, and cerebrospinal fluid; higher total HIV DNA in blood; CD4 depletion in blood and colon; and elevated plasma tumor necrosis factor alpha (TNF-α), C-reactive protein, and D-dimer (all P <.05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNF-α and interleukin 6 were elevated in the ARS group (P <.05) but other biomarkers equilibrated. Conclusions ARS was associated with high viral burden, CD4 depletion, and immune activation across multiple body compartments during AHI and prior to ART. Persistent inflammation despite suppressive ART could contribute to increased morbidity in individuals who experience ARS.

AB - Background Many individuals with acute human immunodeficiency virus infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes. Methods Participants presenting for voluntary human immunodeficiency virus (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers were stratified by ARS diagnosis at enrollment and after up to 96 weeks of antiretroviral therapy (ART). Results From 212382 samples screened, 430 participants were enrolled during AHI, including 335 (78%) with ARS. Median age was 26 years and 416 (97%) were men. Sixty (14%) underwent sigmoid biopsy and 105 (24%) underwent lumbar puncture during AHI. Common symptoms included fever (93%), fatigue (79%), pharyngitis (67%), and headache (64%). Compared to those without ARS, participants with ARS were in later Fiebig stages with higher HIV RNA in blood, colon, and cerebrospinal fluid; higher total HIV DNA in blood; CD4 depletion in blood and colon; and elevated plasma tumor necrosis factor alpha (TNF-α), C-reactive protein, and D-dimer (all P <.05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNF-α and interleukin 6 were elevated in the ARS group (P <.05) but other biomarkers equilibrated. Conclusions ARS was associated with high viral burden, CD4 depletion, and immune activation across multiple body compartments during AHI and prior to ART. Persistent inflammation despite suppressive ART could contribute to increased morbidity in individuals who experience ARS.

KW - CD4 lymphocyte count

KW - HIV

KW - acute retroviral syndrome

KW - highly active antiretroviral therapy

KW - inflammation

UR - http://www.scopus.com/inward/record.url?scp=85047085039&partnerID=8YFLogxK

U2 - 10.1093/cid/cix1063

DO - 10.1093/cid/cix1063

M3 - Article

C2 - 29228130

AN - SCOPUS:85047085039

SN - 1058-4838

VL - 66

SP - 1540

EP - 1549

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 10

ER -

Acute Retroviral Syndrome Is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments

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