Circulating levels of ATP is a biomarker of HIV cognitive impairment.

Abstract

In developed countries, Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART), but still at least half of the HIV infected population shown signs of cognitive impairment. Therefore, biomarkers of HIV cognitive decline are urgently needed. We analyze the opening of one of the larger channels expressed by humans, pannexin-1 (Panx-1) channels, in the uninfected and HIV infected population (n = 175). We determined channel opening and secretion of intracellular second messengers released through the channel such as PGE₂ and ATP. Also, we correlated the opening of Panx-1 channels with the circulating levels of PGE₂ and ATP as well as cogntive status of the individuals analyzed. Here, we demonstrate that Panx-1 channels on fresh PBMCs obtained from uninfected individuals are closed and no significant amounts of PGE₂ and ATP are detected in the circulation. In contrast, in all HIV-infected individuals analyzed, even the ones under effective ART, a spontaneous opening of Panx-1 channels and increased circulating levels of PGE₂ and ATP were detected. Circulating levels of ATP were correlated with cognitive decline in the HIV-infected population supporting that ATP is a biomarker of cognitive disease in the HIV-infected population. We propose that circulating levels of ATP could predict CNS compromise and lead to the breakthroughs necessary to detect and prevent brain compromise in the HIV-infected population.