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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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 languageEnglish
Pages (from-to)1540-1549
Number of pages10
JournalClinical Infectious Diseases
Issue number10
StatePublished - 2 May 2018


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


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