IP-10 Levels as an Accurate Screening Tool to Detect Acute HIV Infection in Resource-Limited Settings

Abstract

Acute HIV infection (AHI) is the period prior to seroconversion characterized by high viral replication, hyper-transmission potential and commonly, non-specific febrile illness. AHI detection requires HIV-RNA viral load (VL) determination, which has very limited access in low-income countries due to restrictive costs and implementation constraints. We sought to identify a biomarker that could enable AHI diagnosis in scarce-resource settings, and to evaluate the feasibility of its implementation. HIV-seronegative adults presenting at the Manhiça District Hospital, Mozambique, with reported-fever were tested for VL. Plasma levels of 49 inflammatory biomarkers from AHI (n = 61) and non-HIV infected outpatients (n = 65) were determined by Luminex and ELISA. IP-10 demonstrated the best predictive power for AHI detection (AUC = 0.88 [95%CI 0.80–0.96]). A cut-off value of IP-10 ≥ 161.6 pg/mL provided a sensitivity of 95.5% (95%CI 85.5–99.5) and a specificity of 76.5% (95%CI 62.5–87.2). The implementation of an IP-10 screening test could avert from 21 to 84 new infections and save from US$176,609 to US$533,467 to the health system per 1,000 tested patients. We conclude that IP-10 is an accurate biomarker to screen febrile HIV-seronegative individuals for subsequent AHI diagnosis with VL. Such an algorithm is a cost-effective strategy to prevent disease progression and a substantial number of further HIV infections.

Dynamics of CD4 and CD8 T-Cell Subsets and Inflammatory Biomarkers during Early and Chronic HIV Infection in Mozambican Adults

“…As described in Section “ Materials and Methods ,” the kinetics of 13 soluble biomarkers with expression levels most significantly different between febrile PHI and HIV-uninfected individuals ( 38 ) were characterized in detail during the first year after infection (Figures 5 A,B; Figure S4 in Supplementary Material). Levels of IP-10, MCP-1, BAFF, soluble (s)CD14, tumor necrosis factor receptor-2 (TNFR2), and TRAIL were highly overexpressed at the first month of infection (M1) and underwent a prompt decrease in the subsequent months.…”

“…Multiplex biomarker profiling was performed for a total of 61 immune response biomarkers in plasma samples. Determinations were performed by ELISA commercial assays or Luminex technology as previously described ( 34 – 38 ). From the resulting 49 quantifiable biomarkers, the difference in the median levels between PHI and non-HIV-infected individuals with reported fever was highly significant for 13 soluble biomarkers ( P < 0.001) ( 38 ).…”

“…Determinations were performed by ELISA commercial assays or Luminex technology as previously described ( 34 – 38 ). From the resulting 49 quantifiable biomarkers, the difference in the median levels between PHI and non-HIV-infected individuals with reported fever was highly significant for 13 soluble biomarkers ( P < 0.001) ( 38 ). In order to represent the dynamics along the first year of infection, these 13 soluble biomarkers were grouped into two main pathways depending on their main function: (1) lymphocyte and monocyte function and (2) inflammation, intestinal damage, cell death, and proliferation.…”

Association between the cytokine storm, immune cell dynamics, and viral replicative capacity in hyperacute HIV infection

“…HIV infection is associated with immune activation which manifests in the elevation of numerous plasma cytokines and chemokines [1][2][3][4][5][6][7]. Notably, the elevation of some plasma cytokines occurs very early after infection, with acute HIV infection (AHI) being characterized by the onset of a cytokine storm in the period leading up to peak viremia [1,2,4,6]. The resolution of the cytokine storm following peak viremia is partial, with some cytokines remaining elevated above pre-infection physiologic levels which persist into the chronic phase in untreated infection.…”

HIV and Human Coronavirus Coinfections: A Historical Perspective

“…In the majority of cases, HIV infection triggers an inflammatory response that presents as acute retroviral syndrome. While this syndrome is normally self-limiting, primary HIV infection can at times lead to a sudden and severe inflammatory process similar to cytokine storm syndrome [40,41]. Whereas this increase in certain plasma cytokines and chemokines occurs very early after infection, cytokine storm is associated with acute HIV infection in the period leading up to peak viremia [41][42][43].…”