Why do HIV patients develop dementia?

Life expectancy for patients with HIV has increased thanks to combination anti-retroviral therapy, but long-term maladies, including dementia, are becoming more prevalent. Almost one-in-two HIV patients are affected by the neurocognitive disorder but how they occur is not fully understood. Researchers in Germany have successfully identified mechanisms detailing how infected cells are able activate brain-specific immune cells which display harmful behaviour and destroy neurons. Their findings – published in Experimental Neurology – could help develop biomarkers to identify risk patients and produce therapeutic strategies against HIV-associated neurocognitive disorders (HAND). “Scientists assume that HIV is harmful to cells directly and that it also triggers indirect mechanisms that lead to nerve cell damage,” explains Dr Simon Faissner from Ruhr Universität Bochum. The HIV virus overcomes the blood-brain barrier by  infecting immune cells such as  monocytes and T cells. Researchers tested the hypothesis that HIV-infected monocytes activate specific immune cells in the brain – microglial cells – by developing a cell culture system to examine the effect of HIV-infected monocytes on these cells. Usually these cells respond by releasing harmful substances, such as cytokines and the researchers simulated the individual steps of HIV infection and measured the concentration of the cytokines released at each stage. Results demonstrated that releasing the viral RNA in the monocytes was a sufficient trigger for maximal microglial activation. Next researchers analysed nerve cells from rat brains to determine if the substances released by the microglial cells could lead to cell death, finding that, compared with the control group, cell death occurred twice as often. “Thanks to our research, we have gained a better understanding of the mechanisms of HIV-associated neurodegeneration,” said Professor Andrew Chan. “These results are likely to contribute to HAND biomarkers becoming established. In the long term, these data may be used to develop therapeutic strategies aiming at retarding HAND progression in HIV-infected patients.” Cytoplasmic HIV-RNA in monocytes determines microglial activation and neuronal cell death in HIV-associated neurodegeneration