Metabolic, glycomic plasma markers linked to HIV remission after ART interruption

Glycomic and metabolic markers in the plasma could help noninvasively determine the duration and probability of HIV remission after antiretroviral therapy (ART) is interrupted, a recent study has found.

The study included two independent cohorts of people living with HIV who had experienced ART interruption (ATI), both of which included several post-treatment controllers, who saw sustained virological suppression even after ART had been terminated.

Plasma analysis revealed that markers that correlated with the probability of viral rebound tended to also associate with the likelihood of viral remission. For example, levels of the anti-inflammatory markers L-glutamic acid, N-acetylglucosamine, and fucose prior to ATI were indicative of delayed rebound, as well as a higher likelihood of achieving viral remission.

On the other hand, pre-ATI plasma concentrations of highly sialylated glycan A3G3S3 correlated with faster rebound and lower chances of viral remission. Glycans containing N-acetylgalactosamine had a similar effect.

Some molecules broke this trend, however, including the digalactosylated G2 glycan on the immunoglobulin G (IgG) glycome. The pre-ATI levels of this biomarker correlated with a longer time to rebound but not with the probability of remission.

The diasialylated IgG glycan also emerged as an exception, with pre-ATI levels correlating only with the probability of remission, but not time to rebound.

“It is not surprising that a single marker cannot highly predict these complicated virological milestones (time to and probability of viral rebound). Therefore, we applied machine-learning algorithms to select the smallest number of variables that, when combined, maximizes the predictive utility of our signatures,” the researchers said.

When used in multivariate models, variables chosen by their algorithms “were able to predict time-to-viral rebound … with a C-index of 74 percent and probability of viral rebound using a logistic model with an area under the curve of 97.5 percent.”