Other potential explanations are the lower levels of immune activation in HIV patients with prolonged viral suppression on ART and confounding effects of demographic and disease-related variables (e.g. age, race, gender, nadir CD4 counts, ART regimen, HCV co-infection, heavy smoking, alcohol and illicit drug abuse, etc.), which increase noise in the analytic pipeline and make it more challenging to identify relevant biomarkers. This evidence concerns the gene CD4 and coinfection.