The neuropathogenesis of AIDS

  title={The neuropathogenesis of AIDS},
  author={Francisco González-Scarano and Julio Mart{\'i}n-Garc{\'i}a},
  journal={Nature Reviews Immunology},
HIV-associated dementia (HAD) is an important complication of the central nervous system in patients who are infected with HIV-1. Although the incidence of HAD has markedly decreased since it has become possible to effectively control viral replication in the blood by administering highly active antiretroviral therapy, a less severe form of HAD, comprising a milder cognitive and motor disorder, is now potentially a serious problem. Brain macrophages and microglia are the key cell types that are… 

Evolving paradigms in the pathogenesis of HIV-1-associated dementia

Mechanisms for neuronal injury and apoptosis, including the role of virus, viral and host proteins, oxidative stress and products of infected or uninfected activated microglia and astrocytes, are explored.

HIV-1 associated dementia: symptoms and causes

HIV-associated cognitive impairment correlates with the increased presence in the CNS of activated, though not necessarily HIV-1-infected, microglia and CNS macrophages, suggesting that indirect mechanisms of neuronal injury and loss/death occur in HIV/AIDS as a basis for dementia since neurons are not themselves productively infected by HIV- 1.

The Role of HIV Infection in Neurologic Injury

This review is aimed at highlighting the virological aspects associated with the onset of neurocognitive disorders and at addressing the novel therapeutic approaches to stop HIV-1 replication in this critical sanctuary.

Neuroimmunology and the pathogenesis of HIV-1 encephalitis in the HAART era: implications for neuroprotective treatment.

Although the advent of highly active antiretroviral therapies (HAART) has made great strides in extending life for AIDS patients, this longer life span may present increasing opportunity for HIV dementia (or HAD) to develop.

Molecular Pathology of Neuro-AIDS (CNS-HIV)

Taken together, the GSK3β and CDK5 signaling pathways are important regulators of neurotoxicity in HIV, and modulation of these factors might have therapeutic potential in the treatment of patients suffering from HIVE.


The results of this study strongly support the role of Vpr in the neuropathogenesis seen during HIVE, and could lead to the development of effective therapeutic treatments necessary to reduce, and possibly prevent, this public health epidemic.

HIV-Associated Neurocognitive Disorders

Treatments that can perturb the viral reservoirs and decrease chronic inflammatory response, in addition to continuing cART, may give the clinician additional tools to prevent HAND.

Roles of MCP-1 in development of HIV-dementia.

This review has attempted to identify mechanisms that induce expression of MCP-1 in the brain and the role that it plays in recruitment of mononuclear cells from blood to brain and in the activation processes of inflammatory and neural cells that lead to development of degenerative changes in the neuronal population.

The shifting patterns of HIV encephalitis neuropathology

More detailed characterization of these proposed variants of HIVE is important in order to better understand the pathogenesis of HIV-associated neurological damage and to design more effective treatments to protect the nervous system.

HIV-associated neurocognitive disorders: a changing pattern

The current clinical trials on neuroprotective agents, and the management of patients with neurocognitive disorders will be discussed.



Correlation between neurological progression and astrocyte apoptosis in HIV‐associated dementia

The data suggest that there is an increased rate of astrocyte loss in the subjects with rapidly progressive dementia, in association with an increased number of HIV DNA–positiveAstrocytes.

Neuronal apoptosis in HIV infection in adults

Neuronal apoptosis was more severe in atrophic brains, and did not directly correlate with productive HIV infection, suggesting an indirect mechanism of neuronal damage is most likely.

Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis.

The pathogenesis of neurological dysfunction associated with human immunodeficiency (HIV)-1 infection is uncertain. However, the presence of macrophage infiltrates in the central nervous system is a

HIV antigen in the brains of patients with the AIDS dementia complex

Human immunodeficiency virus infection was identified immunohistochemically in the brains of 8 patients with acquired immune deficiency syndrome dementia complex. Using a monoclonal antibody against

Immunocytochemical quantitation of human immunodeficiency virus in the brain: Correlations with dementia

It is concluded that the presence of macrophages and microglia is a better correlate with HIV‐associated dementia than is the presence and amount of HIV‐infected cells in the brain.

Rate and Severity of HIV-Associated Dementia (HAD): Correlations with Gp41 and iNOS

It is demonstrated that the severity and rate of progression of HAD correlates significantly with levels of the HIV-1 coat protein, gp41, iNOS, and HAM56, a marker of microglial/macrophage activation.

Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS.

In the final phases of HIV or SIV infection, this chronic, widespread, and dramatic level of macrophage/monocyte/microglial activation constitutes a self-sustaining state of Macrophage dysregulation, which results in pathological alterations and the emergence of various neurological problems.

Caspase Cascades in Human Immunodeficiency Virus-Associated Neurodegeneration

It is demonstrated that HAD is associated with active caspase-3-like immunoreactivity that is localized to the soma and dendrites of neurons in affected regions of the human brain, and suggest that pharmacologic interventions aimed at the casp enzyme pathways may be beneficial for the prevention or treatment of HAD.

Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals.

Astrocytes and endothelial cells are already infected at an early (asymptomatic) stage of the infection and it is suggested that they might contribute to the damage of the CNS.

Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients.

The brains of 12 AIDS patients were studied using in situ hybridization to identify human immunodeficiency virus nucleic acid sequences and immunocytochemistry to identify viral and cellular proteins, suggesting that CNS dysfunction is due to indirect effects rather than neuronal or glial infection.