Trevor A Crowell1,2, Donn J Colby3, Suteeraporn Pinyakorn1,2, James L K Fletcher3, Eugène Kroon3, Alexandra Schuetz1,2,4, Shelly J Krebs1,2, Bonnie M Slike1,2, Louise Leyre5, Nicolas Chomont5, Linda L Jagodzinski1,2, Irini Sereti6, Netanya S Utay7, Robin Dewar8, Rungsun Rerknimitr9, Nitiya Chomchey3, Rapee Trichavaroj4, Victor G Valcour10, Serena Spudich11, Nelson L Michael1, Merlin L Robb1,2, Nittaya Phanuphak3, Jintanat Ananworanich1,2,3,12. 1. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring. 2. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland. 3. SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 4. Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. 5. Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Quebec, Canada. 6. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 7. Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Maryland. 8. Virus Isolation and Serological Laboratory, National Cancer Institute at Frederick, Maryland. 9. Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 10. Memory and Aging Center, Department of Neurology, University of California, San Francisco School of Medicine, New Haven, Connecticut. 11. Department of Neurology, Yale University School of Medicine, New Haven, Connecticut. 12. Department of Global Health, University of Amsterdam, The Netherlands.
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.
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 tumornecrosis 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.
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