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. 2021 Jun 9;11:12176. doi: 10.1038/s41598-021-88052-7

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Representative pathways indicative of neurodegeneration, impairments in bioenergetics, and neuroinflammation correlated with brain HIV RNA load in the frontal cortex. (A–C) The pathway analysis by GSEA demonstrated transcriptional changes that are indicative of neurodegeneration, including pathways representative of gene expression changes in AD, PD, and HD. (D) Gene expression changes indicated a reduction of neuronal signaling that is consistent with synaptodendritic injury, (E–H) impairments in mitochondrial function and energy metabolism, including reductions of TCA cycle, electron transport, and glycolytic genes, (I–L) impairments in RNA synthesis and processing, (M–P) proteostasis and protein synthesis, (Q, R) increased inflammation and cytokine signaling, (S) extracellular matrix, and (T) complement genes. HIV H, high brain HIV RNA load; HIV L, low brain HIV RNA load.