Plasma IP-10 Highly Activated During Acute HIV and Associated With Acute Retroviral Syndrome

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Researchers sought to determine if strong innate immune responses are associated with acute HIV symptoms.

A stronger innate immune response, particularly highly activated plasma IP-10, during acute HIV was found to be associated with acute retroviral syndrome (ARS), according to study results published in Clinical Infectious Diseases.

Researchers obtained data from 55 adults (93% men) with acute HIV from Kenya, Rwanda, Uganda, Zambia, and Sweden to determine if strong innate immune responses are associated with acute HIV symptoms. Patients were grouped based on 11 acute HIV symptoms and other unobserved linkages and were grouped into those with or without ARS. A principal component analysis was used to explore the associations between analytes suggestive of an association with any of the 11 acute HIV symptoms and ARS.

Of the 55 patients, 62% had missing HIV-1 RNA data. There were no baseline differences between those with HIV-1 RNA and those who were missing data; thus, HIV-1 RNA was excluded from the analysis. There were 31 participants with ARS and 24 without ARS (median symptoms per volunteer, 6 and 0.5, respectively). Myalgia was strongly associated with ARS. Although fever was the most frequently reported symptom that occurred in 67% of participants, it was common in participants with and without ARS and thus not a good indicator of ARS.

There were 16 analytes that were significantly elevated during acute HIV when compared with a matched preinfection sample from 31 participants, with plasma IP-10 showing a 14-fold increase (median, 2400 [interquartile range] (IQR), 251-2400] vs 168 [IQR, 86-204] pg/mL). Plasma concentrations of IP-10 were significantly higher across 7 of the 11 acute HIV symptoms. Furthermore, IP-10 was independently associated with ARS (adjusted coefficient, 4.7; 95% CI, 0.8-8.6; P =.002) after adjusting for HIV-1 subtype, age, and risk group.

Principal component analysis identified 36 participants with stronger immune responses, with increased odds of ARS independent of  HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1; 95% CI, 1.7-28.8; P =.003). “IP-10 at threshold [greater than] 466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI, 60.4-96.6) and specificity of 100.0% (95% CI, 90.3-100.0),” the authors reported. In addition, a sensitivity analysis restricted to Fiebig stage II (n=42) samples yielded similar results.

Key limitations included small sample size, missing HIV-1 RNA data, and a predominantly male population.

In the absence of a gold standard, plasma IP-10 may be “…a candidate marker in the differentiation of stronger innate immune responses,” the study authors proposed. “Our findings provide further insights into early immune responses during [acute HIV], their role in the regulation of ARS, and may have implications for the design of vaccine candidates that harness innate immunity for virus neutralization or replication control,” they concluded.


Hassan AS, Hare J, Gounder K, et al. A stronger innate immune response during hyperacute HIV-1 infection is associated with ACUTE retroviral syndrome. Clin Infect Dis. Published online February 15, 2021. doi:10.1093/cid/ciab139