Reduced Immune Activation Predicts Response to Anti-HIV Salvage Therapy

NEW YORK (Reuters Health) Jul 09 - Early decreases in T-cell activation predict a favorable response to antiretroviral salvage therapy in HIV infection, according to a report in the June 1st Journal of Acquired Immune Deficiency Syndromes.

“The results of our study further highlight the relation between HIV disease progression, immune dysfunction, and T-cell activation, because we show that persistent immune activation predicts ongoing viral replication and progressive dysfunction of the CD4+ T-cell population,” Dr. Brett D. Shepard from the Mayo Clinic, Rochester, Minnesota told Reuters Health.

Dr. Shepard, Dr. Andrew Badley and colleagues assessed immune activation and T-cell subsets before and during salvage therapy to identify immunological markers that predict within the first few weeks the subsequent restoration of virologic control in 34 HIV patients.

Higher baseline expression of CD38 on CD4 and CD8 T-cells and lower baseline expression of CD28 on CD4 T-cells were associated with a decreased likelihood of virologic suppression, the researchers report, as were continued high expression of CD38 on CD8 and CD4 T-cells and CD95 on CD4 T-cells.

Patients who showed decreased expression of CD95 and CD38 on CD4 T cells during the first 2 weeks of antiretroviral salvage therapy were significantly more likely to have subsequent virologic suppression, the team found.

In a multivariate model, decreases in expression of CD38 and CD95 between baseline and week 2 of salvage therapy were independently associated with an increased likelihood of subsequent virologic suppression.

The study is the first to show that early decreased immune activation is associated with subsequent virologic suppression, Dr. Shepard said. “These changes in activation occurred independent of viral suppression, because at week 2, when measures of immune activation were improved, 64% of patients still had detectable viral replication.”

“The prognostic value of early measures of CD38 and CD95 expression by CD4+ T cells may provide a distinct advantage to the treating physician, by allowing earlier assessment of the response to changes in salvage therapy,” Dr. Shepard said.

“Moreover, since these measures are based on flow cytometry, incorporating these measures is technically feasible and relatively easy, given that flow cytometry is already being used by the laboratory to measure the CD4+ T-cell count,” he added.

“Further research is needed to find a diagnostic marker that predicts response to antiretroviral therapy that can (1) predict response to therapy within a few days or weeks (as opposed to viral load assays which require a month or more), (2) are less expensive, and (3) are amenable to use in resource-poor settings,” Dr. Shepard concluded. “Our study suggests that measurement of immune activation may represent such a marker, and therefore we encourage other groups to evaluate the prognostic significance of immune activation measurement on the outcome of antiretroviral therapy.”

Source:

1. Reduced Immune Activation Predicts Response to Anti-HIV Salvage Therapy