Elevated immune activation levels linked to increased HIV seroconversion

BRUSSELS — High levels of immune activation were associated with an increased probability of HIV seroconversion, according to a presenter here at EACS 2013.

Yoav Keynan, MD, assistant professor in the department of internal medicine and medical microbiology at the University of Manitoba in Canada, and colleagues said genetic variation in the proinflammatory pathway signaling could trigger higher immune activation and increased susceptibility.

Prior studies have indicated variable susceptibility to HIV among commercial sex workers exposed to HIV, dependent upon higher levels of mucosal and systemic immune activation, which are associated with increased HIV acquisition risk.

To compare levels of immune activation among commercial sex workers in Nairobi, Kenya, the researchers studied an age-matched case-control of 15 cases of seroconversion and 15 controls.

The researchers performed flow cytometry using the T-cell subset typing and immune activation markers. Samples obtained before seroconversion and from the control cohort were compared with immune activation based on three surface markers, including CD69, CD38 and HLA-DR.

Using One Lambda SSP arrays, the researchers examined the genotypes of cytokine production among both cohorts to evaluate genetic diversity. Researchers evaluated tumor necrosis factor (TNF), transforming growth factor (TGF)-beta 1, interleukin (IL)-10, IL-6 and interferon (IFN)-delta and were able to assign high, intermediate and low expression phenotypes.

According to study results, women who acquired HIV infection were able to be identified before acquisition by means of elevated CD69 expression on both CD4 T cells and CD8 T cells. Additionally, researchers identified differences in IFN-delta high level production phenotype between the cohorts.

“Our study demonstrates that individuals with higher level immune activation and higher cytokine-chemokine signaling pathway activity prior to HIV acquisition have a higher likelihood of acquiring the infection,” Keynan said “In addition, we found that a higher expression of several biologically plausible chemokines/cytokines were associated with the predisposing activated phenotype.”

For more information:

Keynan Y.  #BPD 1/1. Presented at: 14th European AIDS Conference; Oct. 16-19, 2013; Brussels.