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. 2018 May 2;66(10):1540-1549.
doi: 10.1093/cid/cix1063.

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

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

Trevor A Crowell et al. Clin Infect Dis. .
Free PMC article

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.

Figures

Figure 1.
Figure 1.
Human immunodeficiency virus (HIV) viral loads in peripheral blood (A), colon (B), and cerebrospinal fluid (CSF) (C). HIV RNA measurements in various body compartments during acute HIV infection (AHI, week 0) and after up to 96 weeks of antiretroviral therapy are compared between participants with and without acute retroviral syndrome (ARS) during AHI. Statistically significant pairwise comparisons (P < .05) are identified.
Figure 2.
Figure 2.
Total and integrated human immunodeficiency virus (HIV) DNA in peripheral blood (A and C) and colon (B and D). Measurements during acute HIV infection (AHI, week 0) and after up to 96 weeks of antiretroviral therapy are compared between participants with and without acute retroviral syndrome (ARS) during AHI. Statistically significant pairwise comparisons (P < .05) are identified.
Figure 3.
Figure 3.
Absolute CD4 (A) and CD8 (B) cell count in peripheral blood, CD4/CD8 ratio in peripheral blood (C), and absolute CD8 count in colon (D). Measurements during acute human immunodeficiency virus (HIV) infection (AHI, week 0) and after up to 96 weeks of antiretroviral therapy are compared between participants with and without acute retroviral syndrome (ARS) during AHI. Statistically significant pairwise comparisons (P < .05) are identified.
Figure 4.
Figure 4.
CD4 and CD8 cell activation in peripheral blood (A and C) and colon (B and D). Measurements during acute human immunodeficiency virus (HIV) infection (AHI, week 0) and after up to 96 weeks of antiretroviral therapy are compared between participants with and without acute retroviral syndrome (ARS) during AHI. Statistically significant pairwise comparisons (P < .05) are identified. Abbreviation: HLA-DR, human leukocyte antigen–D related.
Figure 5.
Figure 5.
Peripheral inflammatory markers. Measurements of TNF-α (A), CRP (B), D-dimer (C), and IL-6 (D) in the peripheral blood during acute human immunodeficiency virus (HIV) infection (AHI, week 0) and after up to 96 weeks of antiretroviral therapy are compared between participants with and without acute retroviral syndrome (ARS) during AHI. Statistically significant pairwise comparisons (P < .05) are identified. Abbreviations: TNF-α, tumor necrosis factor alpha; CRP, C-reactive protein; IL-6, interleukin 6.

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