Author:
|
Pastor, Lucia; Parker, Erica; Carrillo, Jorge; Urrea, Victor; Fuente Soro, Laura; Respeito, Durval; Jairoce, Chenjerai; Mandomando, Inacio; Blanco, Julià; Naniche, Denise
|
Abstract:
|
BACKGROUND: During acute HIV infection (AHI) HIV actively
replicates but seroconversion has not yet occurred. Primary HIV
infection (PHI) is characterized by a transient non-specific
febrile illness, a massive inflammatory response and the
progressive appearance of anti-HIV specific antibodies. In this
study we have identified patterns of inflammatory biomarkers
associated with the innate immunological reaction prior to
completion of a full humoral response. METHODS: A symptom-based
screening was used to identify AHI in the Manhica District
Hospital in Mozambique. Plasma levels of biomarkers were
determined by luminex and ELISA. Anti-HIV antibodies were
analysed by flow-cytometry and Western blot. Statistical
analyses used Random Forest and logistic regression models.
RESULTS: Of 3116 rapid test seronegative or indeterminate
individuals, 85 (2.7%) had positive plasma HIV viral load and
were enrolled as PHI, of which n=45 (52.9%), n=8 (9.4%), n=12
(14.1%) and n=20 (23.5%) were classified as Fiebig I-III, IV, V
and VI stages, respectively by Western-blot. Comparison of
individuals at early (Fiebig I-IV) and late (Fiebig V-VI) immune
stages identified significant differences in the expression
level of plasma BAFF, MCP-1, sCD163 and MIG. This cytokine
signature classified patients in the pre-seroconversion phase
with a sensitivity of 92.5% and a specificity of 81.2%
CONCLUSIONS:: Identification of a cytokine signature specific
for the pre-seroconversion stage of PHI may help to understand
the earliest HIV pathogenic events and identify new potential
targets for immunotherapy aimed at modulating the cytokine
response to HIV infection.This is an open-access article
distributed under the terms of the Creative Commons
Attribution-Non Commercial-No Derivatives License 4.0
(CCBY-NC-ND), where it is permissible to download and share the
work provided it is properly cited. The work cannot be changed
in any way or used commercially without permission from the
journal. |