Abstract
The chronic infection established by the human immunodeficiency virus 1 (HIV-1) produces serious CD4+ T cell immunodeficiency despite the decrease in HIV-1 ribonucleic acid (RNA) levels and the raised life expectancy of people living with HIV-1 (PLWH) through treatment with combined antiretroviral therapies (cART). HIV-1 enters the central nervous system (CNS), where perivascular macrophages and microglia are infected. Serious neurodegenerative symptoms related to HIV-associated neurocognitive disorders (HAND) are produced by infection of the CNS. Despite advances in the treatment of this infection, HAND significantly contribute to morbidity and mortality globally. The pathogenesis and the role of inflammation in HAND are still incompletely understood. Principally, growing evidence shows that the CNS is an anatomical reservoir for viral infection and replication, and that its compartmentalization can trigger the evolution of neurological damage and thus make virus eradication more difficult. In this review, important concepts for understanding HAND and neuropathogenesis as well as the viral proteins involved in the CNS as an anatomical reservoir for HIV infection are discussed. In addition, an overview of the recent advancements towards therapeutic strategies for the treatment of HAND is presented. Further neurological research is needed to address neurodegenerative difficulties in people living with HIV, specifically regarding CNS viral reservoirs and their effects on eradication.
Highlights
Infection provoked by human immunodeficiency virus 1 (HIV-1) is marked by an accelerated reduction in CD4+ T cells,T cell dysfunction, thymic dysfunction, lymphoid destruction, and pan-cellular defects attributed to stem cell dysfunction
To obtain a reliable diagnosis, we need to follow some crucial and standard criteria: the Frascati criteria [36]. These are described according to different levels of severity of the disease, such as asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD), which is the level with the highest severity in HIV-associated neurocognitive disorders (HAND) [7]
Darunavir is an FDA-approved protease inhibitor, widely used in the treatment of people living with HIV-1 (PLWH), with a significantly greater virological response and immunological benefits compared to the standard of care
Summary
Infection provoked by HIV-1 is marked by an accelerated reduction in CD4+ T cells,. T cell dysfunction, thymic dysfunction, lymphoid destruction, and pan-cellular defects attributed to stem cell dysfunction. The possibility to have powerful and affordable virological and immunological parameters can be useful in addressing these problems by providing data about the burden of HIV-1 reservoirs produced by viral replication in diverse anatomical compartments, as well as on permanent inflammation, immune activation, and senescence in spite of favorable virological clearance [26]. For all these reasons, it is important to provide new insights into the assessment and examination of the disease from a virological, immunological, and clinical point of view [26]. The role of different parameters (total HIV-1 DNA, residual viremia, immunological biomarkers) has been the focus of optimized therapies, enhanced pharmacological adherence, and individual examination [26]
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