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Iris More Answers More QST
Iris More Answers More QST
antiviral
Journal of Antimicrobial Chemotherapy (2006) 57, 167–170
doi:10.1093/jac/dki444
Advance Access publication 14 December 2005
The institution of highly active antiretroviral therapy (HAART) in HIV-infected patients restores protective
immune responses against a wide variety of pathogens and dramatically decreases mortality. In a subset of
patients receiving HAART, immune reconstitution is associated with a pathological inflammatory response
leading to substantial short-term morbidity and even mortality. The past several years have seen marked
advances in our clinical understanding of the immune reconstitution inflammatory syndrome (IRIS), but
many questions remain. This article summarizes recent data on clinical risk factors for the development of
IRIS. A consistent finding from multiple groups is that IRIS develops in a substantial percentage of HIV-
infected patients who have an underlying opportunistic infection and receive HAART. As the use of HAART
stands to markedly increase over the next several years, optimal care of patients receiving HAART will need
to incorporate monitoring for and treating complications of IRIS.
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Published by Oxford University Press 2005
Leading article
Initially, the induction of immunity engendered by HAART was majority of IRIS cases have been associated with underlying viral
most clearly demonstrated in the case of hepatitis B virus infection infections (cytomegalovirus, herpes simplex virus, varicella-zoster
where serial antibody measurements could be correlated with virus, and hepatitis C virus) and mycobacteria (either MAI or
the clinical course.10 The measurement of pathogen-specific res- M. tuberculosis).12,14,18 Given that the prevalence of specific
ponses using delayed hypersensitivity testing or more advanced AIDS-related OIs is quite distinct based on locale, it is likely
T-cell techniques demonstrated that IRIS often occurred in the that similar geographical variance will be observed in IRIS cases.
setting of a measurable increase in immune response to an When systematic investigations of IRIS are examined, the per-
underlying OI.20,26 centage of patients developing IRIS and the timing of IRIS onset
following HAART initiation have been surprisingly similar. For
patients with an underlying OI, between 15 and 45% of patients
Movement to define IRIS developed IRIS with the majority of cases presenting within
A major obstacle to quality research on IRIS has been the difficulty 60 days of initiating antiretroviral therapy.13,15,16,19,20 When all
in establishing a definition. The problems in developing a clinically patients receiving HAART were analysed, between 15 and 25%
useful definition included the wide variety of underlying OIs asso- of patients developed IRIS, with most cases again occurring in the
first 3 months of therapy.12,14,18 The reproducibility of the results
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Leading article JAC
antiviral
This finding suggests that clinicians suspicious of IRIS shortly several years on many aspects of IRIS, important questions remain.
after the initiation of HAART should be more attentive to the Further systematic investigations, especially in the areas of patho-
change in HIV-1 RNA levels rather than CD4+ counts when genesis and treatment, are required to optimally care for IRIS
using response to therapy as a criterion for diagnosing IRIS. patients.
Taken together, the data generated by many independent invest-
igators is beginning to clarify our clinical picture of IRIS. Patients
at highest risk for developing IRIS after starting HAART are those
Acknowledgements
with low baseline CD4+ counts or with an underlying OI, two Support for this work was provided by a National Institutes of Health
scenarios that are directly related. Most cases of IRIS can be expec- Mentored Clinical Investigator Award (K12 RR17665) to S. A. S
ted to occur within the first few months of initiating therapy. A and in part by the Department of Veterans Affairs.
brisk immune recovery, in terms of rising CD4+ counts, seems to be
associated with IRIS development, although the CD4+ rise may not
occur until well after a dramatic fall in HIV-1 RNA levels. Import- Transparency declarations
antly, we still lack a definitive answer on whether initiating anti-
None to declare.
169
Leading article
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170