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Therapy Insight: CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome

Abstract

The introduction of combination antiretroviral therapy for HIV infection has prolonged the lives of patients with AIDS. It is increasingly being recognized, however, that following initiation of this therapy some patients can develop a paradoxical neurological deterioration, despite dramatic improvements in HIV viral load and CD4+ T-cell counts. This immune reconstitution inflammatory syndrome (IRIS) in the CNS is emerging as an important neurological complication, particularly as antiretroviral therapy is now becoming readily available worldwide. Currently, there are no guidelines for prevention, diagnosis or treatment of the CNS manifestations of IRIS. Even in patients with an acute presentation, the diagnosis can be challenging. Furthermore, it is possible that more-chronic forms of the syndrome exist but remain unrecognized. Here, we review the various clinical presentations of CNS IRIS, and discuss options for their management.

Key Points

  • Immune reconstitution inflammatory syndrome (IRIS) is a worsening of an HIV patient's clinical condition that is paradoxically attributable to recovery of the immune system after initiation of highly active antiretroviral therapy (HAART)

  • IRIS is set to emerge as an important neurological complication of HIV and HAART, and is likely to have a serious impact on the ability of clinicians to treat large populations with HAART

  • The clinician must be most vigilant for IRIS during the first few months after initiation of HAART

  • A diagnosis of IRIS should be considered even in cases of new occurrence of fever, if the fever occurs soon after starting HAART

  • Histopathology shows a preponderance of CD8+ T cells in IRIS lesions

  • Stopping HAART is not recommended, and the use of systemic corticosteroids is controversial; however, when the inflammatory response from IRIS is causing (or is likely to cause) life-threatening symptoms, systemic corticosteroids may be used

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Figure 1: MRI changes in immune reconstitution inflammatory syndrome (IRIS) associated with cryptococcal meningitis in an HIV-infected patient.
Figure 2: Brain biopsy tissue showing inflammatory infiltrate in immune reconstitution inflammatory syndrome (IRIS)-associated HIV dementia.

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Acknowledgements

The authors' work is supported in part by NIH grants P01MH70056, P01MH070306, R01NS039253 and K08DA016160.

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Correspondence to Avindra Nath.

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Riedel, D., Pardo, C., McArthur, J. et al. Therapy Insight: CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome. Nat Rev Neurol 2, 557–565 (2006). https://doi.org/10.1038/ncpneuro0303

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