Neurological complications of immune reconstitution in HIV‐infected populations

Abstract

The introduction of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection has transformed this disease from a fatal infection to a chronic yet manageable condition by restoring immune function. All the same, this restoration of immune response in some may be associated with deterioration in clinical status, which has been termed immune reconstitution inflammatory syndrome (IRIS). This syndrome often occurs in the context of an underlying opportunistic infection and develops after an interval of weeks to months after the initiation of HAART. Occasionally, IRIS may occur in the brain without any opportunistic infection, which presents as a T cell-mediated encephalitis. This paradoxical infiltration of previously immune suppressed patients with T cells represents a diagnostic challenge and a treatment dilemma. Nonetheless, CNS-IRIS with or without an opportunistic infection can range in severity. Severe cases can be fatal and hence require intervention with steroid treatment. This review discusses the diagnosis, clinical manifestations, risk factors, pathophysiology, and potential treatment strategies of the various forms of IRIS that involve the nervous system.

CNS–Immune Reconstitution Inflammatory Syndrome in the Setting of HIV Infection, Part 1: Overview and Discussion of Progressive Multifocal Leukoencephalopathy–Immune Reconstitution Inflammatory Syndrome and Cryptococcal–Immune Reconstitution Inflammatory Syndrome

“…While this robust inflammatory response is usually self-limiting and often associated with mild symptoms and eventual immune restoration, it can be fulminating, with death ensuing a short time after symptom onset. 1 Furthermore, because IRIS has been reported by many investigators to have an overall incidence at least as high as 25%-35%, increasing to 45% in those with underlying OIs, 2,9,10,16 it significantly negatively impacts the HIV-infected population on HAART by increasing the number of procedures, number of hospitalizations, and the overall morbidity in this patient cohort. 2 Morbidity and mortality rates are even more exaggerated in developing countries, indicating a global health concern.…”

“…12 A biphasic immune reconstitution occurs with the first stage characterized by the prompt release of memory T-cells into the circulation and the second stage typified by a gradual rise in naïve T-cell production. 1 More specifically within the first 2 weeks of HAART, during the first stage of immune restoration, there is a rapid decrease in the HIV viral load. 1 The circulating CD8ϩ T-cells also rapidly increase.…”

“…Pathologically, T-cell infiltration confirms the diagnosis. 1 Conversely, a factor that does not seem to alter the development of IRIS includes the specific type of HAART. 2 For example, patients on protease-containing regimens had a similar risk of the development of IRIS as those HIV-infected individuals on non-protease-containing regimens.…”

“…2 Morbidity and mortality rates are even more exaggerated in developing countries, indicating a global health concern. 1 It is evident, then, that strategies for promptly recognizing and treating patients with IRIS are critical to the ongoing fight against HIV infection in the post-HAART era so that further strides in improving quality of life can be ensured. Also critical is the realization that IRIS might be averted if steps are taken to prevent CD4 counts from dropping below 50 cells per microliter and OI is prevented.…”

“…RIS, first described in 1992, occurs most commonly in the setting of HIV immunosuppression, 1 the focus of this article. When IRIS occurs in HIV-infected individuals, it develops within weeks, months, or, rarely, years after the initiation of HAART and represents an exuberant inflammatory response to an antigen that is either to a dead or dying organism resulting from an OI or a viable pathogen from a persistent infection, or to self-antigens.…”