Neurological opportunistic infections and neurological immune reconstitution syndrome: impact of one decade of highly active antiretroviral treatment in a tertiary hospital

Riveiro‐Barciela, Mar; Falcó, Vicenç; Burgos, Joaquín; Curran, Adrían; Eynde, Eva Van den; Navarro, Jordi; Saz, Sara Villar del; Ocaña, I; Ribera, Esteban; Crespo, Manel; Pahissa, Albert

doi:10.1111/j.1468-1293.2012.01033.x

Cited by 20 publications

(24 citation statements)

References 47 publications

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“…We do not think that our results can be explained by the occurrence of PML-IRIS, even though about 19 % of the PML cases reported in the HAART era are cases of PML-IRIS [32,33]; the radiological findings of the lesions in our cases and their clinical course and onset are not consistent with a diagnosis of PML-IRIS [22,34].…”

Section: Discussioncontrasting

confidence: 78%

Neurological complications of HIV infection in pre-HAART and HAART era: a retrospective study

et al. 2015

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The introduction of highly active anti-retroviral therapy (HAART) led to a radical change in the natural history of HIV infection and of the associated neurological opportunistic infections. However, the mortality of central nervous system (CNS) complications and opportunistic infections is still high in untreated HIV-infected individuals or in patients unaware of their HIV infection. We describe the outcome of HIV-infected patients followed at a single center for AIDS-related neurological syndromes in the 16 years following the introduction of HAART, and compare the findings with those in patients admitted up to 1996. We have conducted a retrospective study of patients with HIV infection or AIDS (based on WHO criteria and classified according to the 1993 CDC criteria) admitted during 20 years (January 1992 to March 2012) to the Infectious Diseases Unit of the University of Verona for the presence of focal or widespread CNS lesion on neuroimaging. Clinical history, CD4 cell count, HIV-RNA level, neurological examination, imaging, cerebrospinal fluid examination and eventual cerebral biopsy results were reviewed as well as the final neurological diagnosis and the treatment. The survival time from the clinical onset of the neurologic syndrome to death was calculated for each patient who died. A statistical analysis was performed comparing data collected up to and after 1996, i.e., before and after HAART introduction. Among 1043 patients with HIV infection or AIDS admitted to the Infectious Diseases Unit of the University of Verona between January 1992 and March 2012, 114 had a CNS lesion. The following diseases were observed: neurotoxoplasmosis (NT), progressive multifocal leukoencephalopathy), primary central nervous system lymphoma (PCNSL), the severe form of HIV-associated neurocognitive disorder, cryptococcal encephalitis (CE) and lesions of undetermined origin. The follow-up period was 4 weeks to 72 months both in the pre-HAART and HAART era. Cerebral lesions were detected in 53/243 patients (21.8%) in the pre-HAART era and in 61/801 patients (7.6%) in the HAART era (p < 0.001). Most patients who developed a neurological complication in the HAART period (40/59, 67.8%) were untreated or did not know to be HIV-infected; in particular, 27.9% of patients with a CNS lesion in the HAART era were unaware of their HIV infection vs 13.2% in the pre-HAART era (p < 0.05). Some patients were not virologically suppressed (14/59, 23.7%) or were immunological non-responders (undetectable viral load, with CD4 count <200 cells/μL; 4/59, 6.8%). Other statistically significant data were the mean age at the onset of neurological complications (32.6 ± 5.4 years in the pre-HAART, 40.3 ± 9.5 in the HAART group, p < 0.001) and the mean CD4 cell count at the onset of illness (median of 38 cells/µL (2-215) in the pre-HAART, 77 cells/µL (2-752) in the HAART group; p < 0.001). In the HAART era a reduction of PCNSL and NT was observed. Our results, while confirming a decrease in the incidence of opportunistic infections of the CNS in the ...

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Section: Discussioncontrasting

confidence: 78%

Neurological complications of HIV infection in pre-HAART and HAART era: a retrospective study

et al. 2015

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“…However, similar to IRIS, CNS-IRIS often occurs within the context of an OI and therefore the incidence of CNS-IRIS is frequently assessed in populations with a particular OI. Thus the incidence of CNS-IRIS is highly variable, averaging 15-25% and ranging upwards of 40% in high-risk individuals (25-29**). A study of 110 consecutive patients with HIV and a diagnosed CNS OI demonstrated the occurrence of CNS-IRIS to be 16.4% (29**).…”

Section: Incidence Of Iris and Cns-irismentioning

confidence: 99%

“…Thus the incidence of CNS-IRIS is highly variable, averaging 15-25% and ranging upwards of 40% in high-risk individuals (25-29**). A study of 110 consecutive patients with HIV and a diagnosed CNS OI demonstrated the occurrence of CNS-IRIS to be 16.4% (29**). Similarly, a study of 620 patients admitted to hospital with new or worsening neurological disease and HIV demonstrated an overall CNS-IRIS incidence of 11.8% (26); however 40% of patients with CNS tuberculosis in this cohort developed CNS-IRIS.…”

Section: Incidence Of Iris and Cns-irismentioning

confidence: 99%

“…Similar trends in mortality were found in another adult (23) and a pediatric cohort (30*). While CNS-IRIS is a smaller proportion of all IRIS cases, it represents the most debilitating form of IRIS and is associated with death or permanent neurological deficit in an estimated 16-50% of cases (27, 29**, 31, 32). The CD4 nadir, an indicator of the degree of immune suppression, and the presence of an OI at the time of initiation of ART are the greatest risk factors for the development of IRIS (3, 22, 33).…”

Section: Iris: Mortality and Risk Factorsmentioning

confidence: 99%

“…Many factors may drive the immune response during IRIS; however the majority of CNS-IRIS cases are associated with an OI. Although ART has contributed to a reduced incidence of CNS OI (29**), OI within the CNS are potent immune stimulators for the restoring immune system and the limited physical space of the brain predisposes it to damage from edema during inflammatory events. Several pathogens are associated with the development of CNS-IRIS but Mycobacterium tuberculosis (25, 34**, 35), Cryptococcus neoformans (34**, 36, 37) and JC virus (38-40) account for the majority of CNS-IRIS incidents.…”

Section: Cns-iris In Association With Opportunistic Infectionmentioning

confidence: 99%

See 2 more Smart Citations

New insights into immune reconstitution inflammatory syndrome of the central nervous system

Johnson

Nath

2014

Current Opinion in HIV and AIDS

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Purpose of review To highlight the importance of immune reconstitution inflammatory syndrome (IRIS) affecting the brain in HIV-infected individuals in the absence of opportunistic infections. To describe the varied clinical manifestations, unifying pathophysiological features and discuss the principles of management of this syndrome. Recent Findings IRIS within the brain is commonly seen in patients with HIV infection upon initiation of antiretroviral drugs. The fulminant forms occur in the face of opportunistic infections or uncontrolled viral replication within the brain. In this case the enhanced immune response is targeted against the microbial agent, and the brain suffers bystander damage. Treatment requires the combination of the antimicrobial agent, continued antiretrovirals and in some cases corticosteroids. It is increasingly being recognized that despite adequate control of viral replication in the brain some patients develop a chronic form of T cell encephalitis which appears to be driven by continued production of HIV-Tat protein. In others the immune response may be targeted against the host antigens in the brain. Summary In patients with CNS-IRIS the use of corticosteroids and strategies that prevent T cell migration into the brain may be needed. Extreme caution is necessary if viral eradication strategies are to employed that involve activation of viral reservoirs, since these patients may be at risk for developing CNS-IRIS.

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Central Nervous System Immune Reconstitution Inflammatory Syndrome

Bahr

Boulware

Marais

et al. 2013

Curr Infect Dis Rep

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Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %–47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %–75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years.

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Neurological opportunistic infections and neurological immune reconstitution syndrome: impact of one decade of highly active antiretroviral treatment in a tertiary hospital

Cited by 20 publications

References 47 publications

Neurological complications of HIV infection in pre-HAART and HAART era: a retrospective study

Neurological complications of HIV infection in pre-HAART and HAART era: a retrospective study

New insights into immune reconstitution inflammatory syndrome of the central nervous system

Central Nervous System Immune Reconstitution Inflammatory Syndrome

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