Introduction: Immunological damage in acute HIV infection (AHI) may predispose to detrimental clinical sequela.
However, studies on the earliest HIV-induced immunological changes are limited, particularly in sub-Saharan Africa.
We assessed the plasma cytokines kinetics, and their associations with virological and immunological parameters, in
a well-characterized AHI cohort where participants were diagnosed before peak viremia.
Methods: Blood cytokine levels were measured using Luminex and ELISA assays pre-infection, during the
hyperacute infection phase (before or at peak viremia, 1–11 days after the first detection of viremia), after peak
viremia (24–32 days), and during the early chronic phase (77–263 days). Gag-protease-driven replicative capacities of
the transmitted/founder viruses were determined using a green fluorescent reporter T cell assay. Complete blood
counts were determined before and immediately following AHI detection before ART initiation.
Results: Untreated AHI was associated with a cytokine storm of 12 out of the 33 cytokines analyzed. Initiation of
ART during Fiebig stages I–II abrogated the cytokine storm. In untreated AHI, virus replicative capacity correlated
positively with IP-10 (rho = 0.84, P < 0.001) and IFN-alpha (rho = 0.59, P = 0.045) and inversely with nadir CD4+ T cell
counts (rho = − 0.58, P = 0.048). Hyperacute HIV infection before the initiation of ART was associated with a transient
increase in monocytes (P < 0.001), decreased lymphocytes (P = 0.011) and eosinophils (P = 0.003) at Fiebig stages I–II,
and decreased eosinophils (P < 0.001) and basophils (P = 0.007) at Fiebig stages III–V. Levels of CXCL13 during the
untreated hyperacute phase correlated inversely with blood eosinophils (rho = − 0.89, P < 0.001), basophils (rho = −
0.87, P = 0.001) and lymphocytes (rho = − 0.81, P = 0.005), suggesting their trafficking into tissues. In early treated
individuals, time to viral load suppression correlated positively with plasma CXCL13 at the early chronic phase
(rho = 0.83, P = 0.042).
Conclusion: While commencement of ART during Fiebig stages I–II of AHI abrogated the HIV-induced cytokine
storm, significant depletions of eosinophils, basophils, and lymphocytes, as well as transient expansions of
monocytes, were still observed in these individuals in the hyperacute phase before the initiation of ART, suggesting
that even ART initiated during the onset of viremia does not abrogate all HIV-induced immune changes