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

Many individuals with acute HIV infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes. We characterized clinical, virologic, and immunologic features of ARS and described the impact of early antiretroviral therapy (ART) initiation. Participants presenting for voluntary 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 ART. From 212,382 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 TNFα, C-reactive protein, and D-dimer (all p-values <0.05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNFα and IL-6 were elevated in the ARS group (p-values <0.05) but other biomarkers equilibrated. 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