PMID- 30362282
OWN - NLM
STAT- MEDLINE
DCOM- 20200512
LR  - 20200512
IS  - 1468-1293 (Electronic)
IS  - 1464-2662 (Linking)
VI  - 20
IP  - 1
DP  - 2019 Jan
TI  - Shedding light on IRIS: from Pathophysiology to Treatment of Cryptococcal 
      Meningitis and Immune Reconstitution Inflammatory Syndrome in HIV-Infected 
      Individuals.
PG  - 1-10
LID - 10.1111/hiv.12676 [doi]
AB  - OBJECTIVES: The aim of this work was to review current treatment options and 
      propose alternatives for immune reconstitution inflammatory syndrome (IRIS) in 
      HIV-infected individuals with cryptococcal meningitis (CM) (termed 'HIV-CM 
      IRIS'). As a consequence of the immunocompromised state of these individuals, the 
      initial immune response to CM is predominantly type 2 T helper (Th2) /Th17 rather 
      than Th1, leading to inefficient fungal clearance at the time of antiretroviral 
      initiation, and a subsequent overexaggeration of the Th1 response and 
      life-threatening IRIS development. METHODS: An article-based and clinical 
      trial-based search was conducted to investigate HIV-CM IRIS pathophysiology and 
      current treatment practices. RESULTS: Guidelines for CM treatment, based on the 
      Cryptococcal Optimal Antiretroviral Timing (COAT) trial, recommend delayed 
      antiretroviral therapy (ART) following antifungal treatment. The approach aims to 
      decrease fungal burden and allow immune balance restoration prior to ART 
      initiation. If the initial immune balance is not restored, the fungal burden is 
      not sufficiently reduced and there is a risk of developing IRIS post-ART, 
      highlighted by a Th1 immune overcompensation, leading to increased mortality. The 
      mainstay treatment for Th1-biased IRIS is corticosteroids; however, this 
      treatment has been shown to correlate with increased mortality and significant 
      associated adverse events. We emphasize targeting a more specific Th1 mechanism 
      via the tumour necrosis factor (TNF)-alpha cytokine antagonist thalidomide, as it is 
      the only TNF-alpha antagonist currently approved for use in infectious disease 
      settings and has been shown to decrease Th1 overreaction, restoring immune 
      balance in HIV-CM IRIS. CONCLUSIONS: Although the side effects and limitations of 
      thalidomide must be considered, it is currently being successfully used in 
      infectious disease settings and warrants mainstream application as a therapeutic 
      option for treatment of IRIS in HIV-infected patients with CM.
CI  - (c) 2018 British HIV Association.
FAU - Balasko, A
AU  - Balasko A
AUID- ORCID: 0000-0001-8732-0485
AD  - Department of Medical Microbiology and Infectious Diseases, University of 
      Manitoba, Winnipeg, MB, Canada.
FAU - Keynan, Y
AU  - Keynan Y
AUID- ORCID: 0000-0003-4948-4707
AD  - Department of Medical Microbiology and Infectious Diseases, University of 
      Manitoba, Winnipeg, MB, Canada.
AD  - Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
AD  - Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, 
      Canada.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20181025
PL  - England
TA  - HIV Med
JT  - HIV medicine
JID - 100897392
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Anti-Retroviral Agents)
RN  - 4Z8R6ORS6L (Thalidomide)
SB  - IM
MH  - AIDS-Related Opportunistic Infections/drug therapy/*immunology
MH  - Adrenal Cortex Hormones/therapeutic use
MH  - Anti-Retroviral Agents/therapeutic use
MH  - Clinical Trials as Topic
MH  - HIV Infections/*drug therapy/immunology/microbiology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/drug therapy/*immunology
MH  - Meningitis, Cryptococcal/drug therapy/*immunology
MH  - Th1 Cells/metabolism
MH  - Th17 Cells/metabolism
MH  - Th2 Cells/metabolism
MH  - Thalidomide/therapeutic use
OTO - NOTNLM
OT  - COAT trial
OT  - HIV/AIDS
OT  - Th1/Th2 balance
OT  - cryptococcal meningitis
OT  - immune reconstitution inflammatory syndrome
OT  - immune restoration
OT  - thalidomide
OT  - tumour necrosis factor-alpha antagonist
EDAT- 2018/10/27 06:00
MHDA- 2020/05/13 06:00
CRDT- 2018/10/27 06:00
PHST- 2018/08/10 00:00 [accepted]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2020/05/13 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
AID - 10.1111/hiv.12676 [doi]
PST - ppublish
SO  - HIV Med. 2019 Jan;20(1):1-10. doi: 10.1111/hiv.12676. Epub 2018 Oct 25.