Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid

Direct infection of the central nervous system by human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, was not appreciated in the early years of the AIDS epidemic. Neurological complications associated with AIDS were largely attributed to opportunistic infections that arose as a result of the immunocompromised state of the patient and to depression. In 1985, several groups succeeded in isolating HIV-1 directly from brain tissue. Also that year, the viral genome was completely sequenced, and HIV-1 was found to belong to a neurotropic subfamily of retrovirus known as the Lentivirinae. These findings clearly indicated that direct HIV-1 infection of the central nervous system played a role in the development of AIDS-related neurological disease. This review summarizes the clinical manifestations of HIV-1 infection of the central nervous system and the related neuropathology, the tropism of HIV-1 for specific cell types both within and outside of the nervous system, the possible mechanisms by which HIV-1 damages the nervous system, and the current strategies for diagnosis and treatment of HIV-1-associated neuropathology.

Download Full-text

Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells

Clinical Infectious Diseases ◽

10.1093/cid/ciy1066 ◽

2018 ◽

Vol 69 (8) ◽

pp. 1345-1352 ◽

Cited By ~ 15

Author(s):

Sarah B Joseph ◽

Laura P Kincer ◽

Natalie M Bowman ◽

Chris Evans ◽

Michael J Vinikoor ◽

...

Keyword(s):

Central Nervous System ◽

Human Immunodeficiency Virus ◽

Nervous System ◽

Antiretroviral Therapy ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Csf Escape

Abstract Background Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs. Methods We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points. Results For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was ≥0.5 log copies/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity. Conclusions Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs.

Download Full-text