Chapter 13 - CNS immune reconstitution inflammatory syndrome
Section snippets
Introduction to IRIS
With the advent of combination antiretroviral therapy (cART) in 1996, reports of atypical presentations of well-described opportunistic infections following induction of antiretroviral therapy began to appear in the medical human immunodeficiency virus (HIV) literature. In 1997 and 1998, The Lancet published two case series of patients with absolute CD4 + T-cell counts below 50 cells/μL who responded to antiretroviral therapy with a two- to threefold increase in baseline CD4 T-cell levels. These
Animal models for IRIS
Several animal models have been created to attempt to identify the mechanisms underpinning IRIS pathophysiology, many supporting the role of dysregulated CD4 + and CD8 + T-cell cascades (Table 13.1). Newer mouse models have also looked at the role of checkpoint inhibitors, such as programmed cell death protein 1 (PD-1) in IRIS. PD-1 is expressed on both B and T cells, and is involved in establishing immune tolerance. In humans, it is upregulated in chronic viral infections, marking “immune
Opportunistic infections
Patterns of CNS IRIS are disease-specific – with each individual opportunistic infection in the setting of HIV and immune reconstitution there will often be a unique inflammatory pattern on imaging. Brain MRI is the imaging modality of choice in patients with suspected CNS IRIS and combination MRI sequences can be used as additional evidence of CNS IRIS. In a study of HIV-positive, post-cART population with CNS IRIS, four MRI characteristics were felt to be predictive: intrinsic T1
IRIS management
The mainstay of treatment is to control the inflammation since inflammation can cause bystander damage to the brain (Fig. 13.4). Since IRIS occurs in the context of an underlying infection, the flip side of controlling the inflammation is that the infection may become unchecked and thus cause harm. Hence several scenarios need to be considered before anti-inflammatory therapy is used.
- 1.
When an effective antimicrobial agent is available for treating the underlying infection: infections such as
Specific immune modulators
Ideally we need drugs that would preserve the immune responses directed against the microbial pathogen but downregulate the bystander effects on the surrounding brain tissue. This can only be accomplished if we develop a better understanding of the underlying pathophysiologic mechanisms that mediate these immune responses. However, for some infections such as cryptococcal infection we need to develop better mechanisms to clear the antigen from the CNS, since current fungicidal agents may kill
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Cited by (27)
Good Gone Bad: Complications of Chemotherapy, Immunotherapy, and Radiotherapy on the CNS
2024, Current Problems in Diagnostic RadiologyGuillain-Barré syndrome spectrum as manifestation of HIV-related immune reconstitution inflammatory syndrome: case report and literature review
2022, Brazilian Journal of Infectious DiseasesCitation Excerpt :All but one patient with available information received IVIG and only two patients had total recovery (Table 1). Corticosteroids are the mainstay of central nervous system IRIS therapy,18 but there is no information in IRIS-related SGB spectrum. IRIS-related overlapping GBS and BBE is a possible manifestation in HIV-infected patients.
Non-infectious mechanisms of neurological damage due to infection
2021, Journal of the Neurological SciencesCitation Excerpt :A persistent infection might activate chronically immune defense mechanisms in the host to control the infection but possibly this activation might persist even when the infectious agent is not present anymore. A typical example is immune reconstitution inflammatory syndrome (IRIS) in patients with human immune deficiency virus (HIV) infection or with progressive multifocal leukoencephalopathy (PML) due to John Cunningham (JC) virus infection [2,3]. The immune response is exceeding by far the necessary reaction to control the infectious agent and is capable by itself of causing damage to the brain only to be controlled with immune suppression like steroids [4,5].
Ongoing Healthcare Disparities in neuroHIV: Addressing Gaps in the Care Continuum
2023, Current HIV/AIDS Reports