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.
Highlights
As viraemia increases during Acute HIV infection (AHI), there is a striking cascade response of inflammatory cytokines[2]
There were no significant differences in age, gender or malaria status by study group (p > 0.1)
We have demonstrated that among 49 inflammatory biomarkers assessed, the IP-10 cytokine has the highest accuracy in identifying individuals with AHI in a cohort of febrile HIV-seronegative individuals
Summary
As viraemia increases during AHI, there is a striking cascade response of inflammatory cytokines[2]. Significant efforts have been made to characterise host and viral proteins present during AHI aiming to identify biomarkers www.nature.com/scientificreports/. Of progression or key pathological pathways that could be targeted to minimize HIV-induced immune damage over the course of infection[2, 16,17,18,19]. In the present study we sought to determine whether a single or a combination of biomarkers could differentiate individuals in AHI from non-HIV infected individuals within a population of patients reporting febrile symptoms at a rural hospital in Southern Mozambique. Once plasma level of IP-10 was identified as candidate biomarker, we assessed the cost-effectiveness of implementing it for AHI diagnosis in low-income settings
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