The greater the calming effect of antiretroviral (ARV) therapy on the immune system during the first few weeks of treatment, the better the chance of maintaining an undetectable viral load over time, according to a new study published in the June 1 issue of the Journal of Acquired Immune Deficiency Syndromes.

There is mounting evidence that much of the immune system damage caused by HIV—including the very high rate of HIV replication in the body—is due to an overactive immune response to the virus. High levels of certain types of T cells, dubbed CD38+ and CD95+ cells, are considered to be markers of an overactive immune response in people living with HIV.

Brett Shepard, MD, PhD, from the Mayo Clinic in Rochester, Minnesota, and his colleagues theorized that early changes in these activated immune system cells in response to treatment might help predict the effects of therapy on viral load and CD4 cell counts. Because ARV therapy may take several months to reduce viral load to undetectable levels, finding reliable markers other than viral load could help predict whether a drug regimen is likely to achieve undetectable virus levels, especially for those with HIV resistant to multiple ARVs.

Shepard’s group enrolled 34 heavily treatment-experienced HIV-positive patients in a study to examine the impact of early changes to CD38+ and CD95+ T cell levels. The majority of the patients were white males, and nearly all were in their early 40s. Most had been using ARV treatments for 10 or more years. Extensive analysis of the patients’ viruses and immune cells were carried out before and after starting a new ARV regimen.

The investigators found that the patients whose CD38+ and CD95+ T cells dropped significantly within two weeks after starting treatment were much more likely to ultimately achieve and maintain an undetectable viral load.

Though previous studies have shown that reducing immune activation predicts CD4 cell gains in people who are new to ARV treatment, this is the first study to show that changes in immune activation predict viral load response rates in people who are heavily treatment experienced. The authors are recommending that further studies be conducted to validate these results.