Kevin Robertson, PhD, Investigator, University of North Carolina, Chapel Hill Clinical Research Site

A5303 was entitled “Systemic Inflammatory and Immune Biomarkers in Neurocognitive Changes with Initial ART” and was the largest randomized clinical trial studying neurocognitive outcomes ever conducted in the United States with over 200 treatment naïve participants who were followed after ART initiation for 48 weeks. Within the HIV research community, considerable interest in neurocognitive impairment in HIV as well as the desire to better understand the underlying pathogenesis of HIV-associated neurocognitive disorder (HAND). Biomarkers are an important way of looking at that pathogenesis to try to understand how HAND develops, and why it continues in some on effective antiretroviral therapy.

A5303 researchers found correlations between activated T cells and neurocognitive performance at baseline when viral loads are high, but these correlations were not there after the virus was suppressed with treatment. However, after the virus was suppressed, there were correlations between monocytes and neurocognitive impairment, not there at baseline. This finding fits some theories of which cells (monocytes) are driving HAND. These findings suggest that the driving mechanism behind HAND before ART and on ART may be different. In large part, A5303 confirmed that biomarkers in the periphery, (the blood) provided only weak correlations with neurocognitive impairment, and are likely too distant from the brain to be predictive. Biomarkers from Cerebrospinal Fluid (CSF) are likely more reflective of processes in the brain and central nervous system. 

A5303 established that only a few biomarkers sampled in the blood were related to neurocognitive impairment. There is still a need to better understand the pathogenesis underlying continued neurocognitive impairment, and to continue looking for the causes to be able to better treat and prevent HAND. 

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