--- - |2+ Abstract Since the success of combined antiretroviral therapy, HIV‐1‐infected individuals are now living much longer. This increased life expectancy is accompanied by a higher prevalence of HIV‐1 associated neurocognitive disorders. Rising too is the incidence in these patients of pathological hallmarks of Alzheimer's disease such as increased deposition of amyloid beta protein (Aβ). Although neurons are major sources of Aβ in the brain, astrocytes are the most numerous glial cells, therefore, even a small level of astrocytic Aβ metabolism could make a significant contribution to brain pathology. Neprilysin (NEP) is a decisive/crucial regulator of Aβ levels. We evaluated the effects of HIV‐1 on Aβ deposition and the expression and activity of NEP in primary human astrocytes. Specifically, no differences in intracellular amyloid deposits were found between infected and control cells. However, primary cultures of infected astrocytes showed more extracellular Aβ levels compared to controls. This was accompanied by reduced expression of NEP and to a significant decrease on its activity. These results indicate that the presence of HIV‐1 in the brain could contribute to the increase of the total burden of cerebral Aβ. This article is protected by copyright. All rights reserved - 'Journal of Cellular Physiology, Volume 0, Issue ja, -Not available-. '