JAC
antiviral
Journal of Antimicrobial Chemotherapy (2006) 57, 167–170
doi:10.1093/jac/dki444
Advance Access publication 14 December 2005
Immune reconstitution inflammatory syndrome:
more answers, more questions
Samuel A. Shelburne1, Martin Montes1 and Richard J. Hamill1,2*
1
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, 1 Baylor Plaza,
Houston, TX 77030, USA; 2Department of Medicine, Section of Infectious Diseases (111G),
Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard,
Houston, TX 77030, USA
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
Downloaded from http://jac.oxfordjournals.org/ by guest on January 8, 2016
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.
Keywords: HIV, HAART, paradoxical reaction, restoration
Introduction Historical view of IRIS in HIV- and
non-HIV-infected patients
The development of highly active antiretroviral therapy (HAART)
has markedly improved the outlook for patients infected with HIV.1 While recognition of IRIS did not become widespread until after
While the receipt of HAART engenders protective immune the introduction of HAART in the mid-1990s, prior to this point
responses against a wide variety of pathogens, for some patients there was ample appreciation that improvement in immune func-
a profound, pathological inflammatory reaction ensues targeted at tion could result in pathological inflammation. The so-called para-
either subclinical or previously recognized microbes.2–4 The doxical responses were well described among non-HIV-infected
inflammatory response can result in a spectrum of presentations patients treated for Mycobacterium tuberculosis (MTB)
ranging from clinical worsening of a treated opportunistic infection infection.21 Clinical worsening in these patients following initi-
(OI), atypical appearance of an unrecognized OI to even autoim- ation of anti-MTB therapy had been attributed to a reversal of
mune disorders such as Graves’ disease.5–7 A multitude of names the immunosuppression that MTB infection induces and was
have been applied to these situations including immune restoration associated with conversion of MTB skin tests from negative to
disease and immune reconstitution inflammatory syndrome positive.21 Inflammatory reactions during treatment are also rou-
(IRIS).2–5 tine in patients infected with Mycobacterium leprae.22 Finally,
Most of the original descriptions of IRIS consisted of case recovery of immune cells following bone marrow transplantation
reports or case series of small numbers of patients.8–10 More or chemotherapy has been clearly associated with clinical deteri-
recently, numerous groups have published cohort studies regarding oration for some patients.23
incidence, risk factors and timing of onset of IRIS among patients That such inflammatory responses might occur among HIV
receiving HAART.11–20 These investigations have provided the patients was first recognized when zidovudine monotherapy res-
required information for clinicians treating HIV-infected patients, ulted in atypical, localized presentations of Mycobacterium avium
but much uncertainty remains. Moreover, the dearth of patholo- intracellulare (MAI) infection.24 The introduction of HAART
gical data means that our understanding of the mechanisms of IRIS was quickly followed by numerous reports of patients in whom
remains at a rudimentary level. recovery of immune responses led to clinical worsening.8,10,25
.............................................................................................................................................................................................................................................................................................................................................................................................................................
*Corresponding author. Tel: +713-794-7835; Fax: +713-794-7045; E-mail:
.............................................................................................................................................................................................................................................................................................................................................................................................................................
167
Published by Oxford University Press 2005
antiviral
Journal of Antimicrobial Chemotherapy (2006) 57, 167–170
doi:10.1093/jac/dki444
Advance Access publication 14 December 2005
Immune reconstitution inflammatory syndrome:
more answers, more questions
Samuel A. Shelburne1, Martin Montes1 and Richard J. Hamill1,2*
1
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, 1 Baylor Plaza,
Houston, TX 77030, USA; 2Department of Medicine, Section of Infectious Diseases (111G),
Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard,
Houston, TX 77030, USA
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
Downloaded from http://jac.oxfordjournals.org/ by guest on January 8, 2016
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.
Keywords: HIV, HAART, paradoxical reaction, restoration
Introduction Historical view of IRIS in HIV- and
non-HIV-infected patients
The development of highly active antiretroviral therapy (HAART)
has markedly improved the outlook for patients infected with HIV.1 While recognition of IRIS did not become widespread until after
While the receipt of HAART engenders protective immune the introduction of HAART in the mid-1990s, prior to this point
responses against a wide variety of pathogens, for some patients there was ample appreciation that improvement in immune func-
a profound, pathological inflammatory reaction ensues targeted at tion could result in pathological inflammation. The so-called para-
either subclinical or previously recognized microbes.2–4 The doxical responses were well described among non-HIV-infected
inflammatory response can result in a spectrum of presentations patients treated for Mycobacterium tuberculosis (MTB)
ranging from clinical worsening of a treated opportunistic infection infection.21 Clinical worsening in these patients following initi-
(OI), atypical appearance of an unrecognized OI to even autoim- ation of anti-MTB therapy had been attributed to a reversal of
mune disorders such as Graves’ disease.5–7 A multitude of names the immunosuppression that MTB infection induces and was
have been applied to these situations including immune restoration associated with conversion of MTB skin tests from negative to
disease and immune reconstitution inflammatory syndrome positive.21 Inflammatory reactions during treatment are also rou-
(IRIS).2–5 tine in patients infected with Mycobacterium leprae.22 Finally,
Most of the original descriptions of IRIS consisted of case recovery of immune cells following bone marrow transplantation
reports or case series of small numbers of patients.8–10 More or chemotherapy has been clearly associated with clinical deteri-
recently, numerous groups have published cohort studies regarding oration for some patients.23
incidence, risk factors and timing of onset of IRIS among patients That such inflammatory responses might occur among HIV
receiving HAART.11–20 These investigations have provided the patients was first recognized when zidovudine monotherapy res-
required information for clinicians treating HIV-infected patients, ulted in atypical, localized presentations of Mycobacterium avium
but much uncertainty remains. Moreover, the dearth of patholo- intracellulare (MAI) infection.24 The introduction of HAART
gical data means that our understanding of the mechanisms of IRIS was quickly followed by numerous reports of patients in whom
remains at a rudimentary level. recovery of immune responses led to clinical worsening.8,10,25
.............................................................................................................................................................................................................................................................................................................................................................................................................................
*Corresponding author. Tel: +713-794-7835; Fax: +713-794-7045; E-mail:
.............................................................................................................................................................................................................................................................................................................................................................................................................................
167
Published by Oxford University Press 2005
