Skip to main content
Top
Published in: AIDS Research and Therapy 1/2017

Open Access 01-12-2017 | Research

Hospital days attributable to immune reconstitution inflammatory syndrome in persons living with HIV before and after the 2012 DHHS HIV guidelines

Authors: Peter Liu, Rebecca Dillingham, Kathleen A. McManus

Published in: AIDS Research and Therapy | Issue 1/2017

Login to get access

Abstract

Background

Immune reconstitution inflammatory syndrome (IRIS) can manifest with initiation or reintroduction of antiretroviral therapy (ART) in persons living with HIV (PLWH). In 2012, updated United States treatment guidelines recommended initiation of ART for all PLWH regardless of CD4 count. The objectives of this study were to quantify hospital usage attributable to IRIS and assess the reasons for hospitalization in PLWH before and after the guideline update.

Methods

Subjects were PLWH between 18–89 years of age who were hospitalized between November 1, 2009 and July 31, 2014. Equivalent time periods before and after updated treatment guidelines were considered, and designated as Time Period 1 and Time Period 2, respectively. IRIS-attributable hospitalizations were identified by ICD9 codes and electronic medical record searches with subsequent review and confirmation. For hospitalizations that were not confirmed as being IRIS-attributable, primary discharge diagnoses were reviewed.

Results

A total of 278 PLWH were hospitalized 521 times throughout the study period. Time Period 1 had 9 PLWH with 12 IRIS-attributable hospitalizations while Time Period 2 had 6 PLWH with 9 IRIS-attributable hospitalizations. A larger proportion of IRIS-attributable hospital days was observed in Time Period 1 compared to Time Period 2 (7.5 vs 4.2%; p < 0.001). Median length of stay for IRIS-attributable hospitalizations was longer than for other diagnoses, particularly during Time Period 1 (12.0 vs 4.0; p = 0.05). The most common causes for hospitalizations in PLWH were non AIDS-defining infection, AIDS-defining malignancy, and gastrointestinal. PLWH who had HIV viral suppression (<200 copies/mL) accounted for 34 and 24% of hospitalizations in Time Periods 1 and 2 respectively.

Conclusions

Hospitalizations for PLWH continue at high rates and IRIS is a significant contributing factor. In our single-center study, there was a lower number of IRIS-attributable hospitalizations and IRIS-attributable hospital days in Time Period 2 compared with Time Period 1. The hospital burden of IRIS may decrease over time as more PLWH are started on ART earlier in the course of infection. This study highlights the continued importance of early diagnosis and linkage to care of those infected with HIV, so that morbidity and costs associated with IRIS continue to decline.
Literature
1.
go back to reference Shelburne S, Hamill R, Rodriguez-Barradas M. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine. 2002;81(3):213–27.CrossRefPubMed Shelburne S, Hamill R, Rodriguez-Barradas M. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine. 2002;81(3):213–27.CrossRefPubMed
2.
go back to reference May M, Gompels M, Delpech V. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS. 2014;28:1193–202.CrossRefPubMedPubMedCentral May M, Gompels M, Delpech V. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS. 2014;28:1193–202.CrossRefPubMedPubMedCentral
3.
go back to reference Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Curr Opin HIV AIDS. 2016;11(5):492–500 [Epub ahead of print].CrossRefPubMed Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Curr Opin HIV AIDS. 2016;11(5):492–500 [Epub ahead of print].CrossRefPubMed
4.
go back to reference Teeraananchai S, Kerr S, Ruxrungtham K. Life expectancy of HIV-positive people after starting combination antiretroviral therapy: a meta-analysis. HIV Med [Epub ahead of print]. Teeraananchai S, Kerr S, Ruxrungtham K. Life expectancy of HIV-positive people after starting combination antiretroviral therapy: a meta-analysis. HIV Med [Epub ahead of print].
6.
go back to reference Serrano-Villar S, Perez-Elias M, Dronda F. Increased Risk of Serious Non-AIDS-Related Events in HIV-Infected Subjects on Antiretroviral Therapy Associated with a Low CD4/CD8 Ratio. PLoS One. 2013;9(1):e85798. doi:10.1371/journal.pone.0085798.CrossRef Serrano-Villar S, Perez-Elias M, Dronda F. Increased Risk of Serious Non-AIDS-Related Events in HIV-Infected Subjects on Antiretroviral Therapy Associated with a Low CD4/CD8 Ratio. PLoS One. 2013;9(1):e85798. doi:10.​1371/​journal.​pone.​0085798.CrossRef
7.
go back to reference Muller M, Wandel S, Colebunders R. Incidence and lethality of immune reconstitution disease in HIV-infected patients starting antiretroviral therapy: systematic review and meta-analysis. Lancet Infect Dis. 2010;10(4):251–61.CrossRefPubMedPubMedCentral Muller M, Wandel S, Colebunders R. Incidence and lethality of immune reconstitution disease in HIV-infected patients starting antiretroviral therapy: systematic review and meta-analysis. Lancet Infect Dis. 2010;10(4):251–61.CrossRefPubMedPubMedCentral
8.
go back to reference French M, Price P, Stone S. Immune restoration disease after antiretroviral therapy. AIDS. 2004;18(12):1615–27.CrossRefPubMed French M, Price P, Stone S. Immune restoration disease after antiretroviral therapy. AIDS. 2004;18(12):1615–27.CrossRefPubMed
9.
go back to reference DeSimone J, Pomerantz R, Babinchak T. Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy. Ann Intern Med. 2000;133(6):447–54.CrossRefPubMed DeSimone J, Pomerantz R, Babinchak T. Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy. Ann Intern Med. 2000;133(6):447–54.CrossRefPubMed
10.
go back to reference French M, Lenzo N, John M. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med. 2001;1(2):107–15.CrossRef French M, Lenzo N, John M. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med. 2001;1(2):107–15.CrossRef
11.
go back to reference Jevtovic D, Salemovic D, Ranin J. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Med. 2005;6(2):140–3.CrossRefPubMed Jevtovic D, Salemovic D, Ranin J. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Med. 2005;6(2):140–3.CrossRefPubMed
12.
go back to reference Ratnam I, Chiu C, Kandala N. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1–Infected cohort. Clin Infect Dis. 2006;42(3):418–27.CrossRefPubMed Ratnam I, Chiu C, Kandala N. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1–Infected cohort. Clin Infect Dis. 2006;42(3):418–27.CrossRefPubMed
13.
go back to reference Park WB, Choe PG, Jo JH. Tuberculosis manifested by immune reconstitution inflammatory syndrome during HAART. AIDS. 2007;21(7):875–7.CrossRefPubMed Park WB, Choe PG, Jo JH. Tuberculosis manifested by immune reconstitution inflammatory syndrome during HAART. AIDS. 2007;21(7):875–7.CrossRefPubMed
14.
go back to reference Jenny-Avital E, Abadi M. Immune reconstitution cryptococcosis after initiation of successful highly active antiretroviral therapy. Clin Infect Dis. 2002;35(12):128–33.CrossRef Jenny-Avital E, Abadi M. Immune reconstitution cryptococcosis after initiation of successful highly active antiretroviral therapy. Clin Infect Dis. 2002;35(12):128–33.CrossRef
15.
go back to reference Davies M, Meintjes G. Assessing the contribution of the immune reconstitution inflammatory syndrome to mortality in developing country antiretroviral therapy programs. Clin Infect Dis. 2009;49(6):973–5.CrossRefPubMedPubMedCentral Davies M, Meintjes G. Assessing the contribution of the immune reconstitution inflammatory syndrome to mortality in developing country antiretroviral therapy programs. Clin Infect Dis. 2009;49(6):973–5.CrossRefPubMedPubMedCentral
16.
go back to reference Seydi M, Manga N, Dieng A. Immune reconstitution syndrome during antiretroviral therapy in senegal. Infect Dis Med. 2009;39(5):350–1. Seydi M, Manga N, Dieng A. Immune reconstitution syndrome during antiretroviral therapy in senegal. Infect Dis Med. 2009;39(5):350–1.
17.
go back to reference Mayer K, French M. Immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis. 2009;48(1):101–7.CrossRef Mayer K, French M. Immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis. 2009;48(1):101–7.CrossRef
18.
go back to reference Mahnke Y, Greenwald J, DerSimonian R. Selective expansion of polyfunctional pathogen-specific CD4+ T cells in HIV-1-infected patients with immune reconstitution inflammatory syndrome. Blood. 2012;119(13):3105–12.CrossRefPubMedPubMedCentral Mahnke Y, Greenwald J, DerSimonian R. Selective expansion of polyfunctional pathogen-specific CD4+ T cells in HIV-1-infected patients with immune reconstitution inflammatory syndrome. Blood. 2012;119(13):3105–12.CrossRefPubMedPubMedCentral
19.
go back to reference Kestens L, Seddiki N, Bohjanen P. Immunopathogenesis of immune reconstitution disease in HIV patients responding to antiretroviral therapy. Curr Opin HIV AIDS. 2008;3(4):419–24.CrossRefPubMedPubMedCentral Kestens L, Seddiki N, Bohjanen P. Immunopathogenesis of immune reconstitution disease in HIV patients responding to antiretroviral therapy. Curr Opin HIV AIDS. 2008;3(4):419–24.CrossRefPubMedPubMedCentral
20.
go back to reference Tadokera R, Meintjes G, Skolimowska K. Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome. Eur Respir J. 2011;37(5):1248–59.CrossRefPubMed Tadokera R, Meintjes G, Skolimowska K. Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome. Eur Respir J. 2011;37(5):1248–59.CrossRefPubMed
21.
go back to reference Boulware D, Meya D, Bergemann T. Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study. PLOS Med. 2010;7(12):e1000384.CrossRefPubMedPubMedCentral Boulware D, Meya D, Bergemann T. Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study. PLOS Med. 2010;7(12):e1000384.CrossRefPubMedPubMedCentral
22.
go back to reference Shelburne S, Darcourt J, White C. The role of immune reconstitution inflammatory syndrome in AIDS-related cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis. 2005;40(7):1049–52.CrossRefPubMed Shelburne S, Darcourt J, White C. The role of immune reconstitution inflammatory syndrome in AIDS-related cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis. 2005;40(7):1049–52.CrossRefPubMed
23.
go back to reference Sharma S, Soneja M. HIV & immune reconstitution inflammatory syndrome (IRIS). Indian J Med. 2011;134:866–77.CrossRef Sharma S, Soneja M. HIV & immune reconstitution inflammatory syndrome (IRIS). Indian J Med. 2011;134:866–77.CrossRef
24.
go back to reference Piliero P, Fish D, Preston S. Guillain-barré syndrome associated with immune reconstitution. Clin Infect Dis. 2003;36(9):111–1114.CrossRef Piliero P, Fish D, Preston S. Guillain-barré syndrome associated with immune reconstitution. Clin Infect Dis. 2003;36(9):111–1114.CrossRef
25.
go back to reference Seddiki N, Sasson S, Santner-Nanan B. Proliferation of weakly suppressive regulatory CD4+ T cells is associated with over-active CD4+ T-cell responses in HIV-positive patients with mycobacterial immune restoration disease. Eur J Immunol. 2009;39(2):391–403.CrossRefPubMed Seddiki N, Sasson S, Santner-Nanan B. Proliferation of weakly suppressive regulatory CD4+ T cells is associated with over-active CD4+ T-cell responses in HIV-positive patients with mycobacterial immune restoration disease. Eur J Immunol. 2009;39(2):391–403.CrossRefPubMed
26.
go back to reference Walker N, Scriven J, Meintjes G. Immune reconstitution inflammatory syndrome in HIV-infected patients. HIV AIDS Res Palliat Care. 2015;7:49–64. Walker N, Scriven J, Meintjes G. Immune reconstitution inflammatory syndrome in HIV-infected patients. HIV AIDS Res Palliat Care. 2015;7:49–64.
27.
go back to reference Barber D, Andrade B, Sereti I. Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none. Nat Rev Microbiol. 2012;10(2):150–6.PubMedPubMedCentral Barber D, Andrade B, Sereti I. Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none. Nat Rev Microbiol. 2012;10(2):150–6.PubMedPubMedCentral
28.
29.
go back to reference Marais S, Meintjes G, Pepper D. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome. Clin Infect Dis. 2013;56(3):450–60.CrossRefPubMed Marais S, Meintjes G, Pepper D. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome. Clin Infect Dis. 2013;56(3):450–60.CrossRefPubMed
33.
go back to reference Lortholary O, Arnuad F, Mamain N. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS. 2005;19(10):1043–9.CrossRefPubMed Lortholary O, Arnuad F, Mamain N. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS. 2005;19(10):1043–9.CrossRefPubMed
34.
go back to reference Breton G, Duval X, Estellat C. Determinants of immune reconstitution inflammatory syndrome in HIV Type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Clin Infect Dis. 2004;39(11):1709–12.CrossRefPubMed Breton G, Duval X, Estellat C. Determinants of immune reconstitution inflammatory syndrome in HIV Type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Clin Infect Dis. 2004;39(11):1709–12.CrossRefPubMed
36.
go back to reference Turner B, Cunningham W, Duan N. Delayed medical care after diagnosis in a US national probability sample of persons infected with human immunodeficiency virus. Arch Intern Med. 2000;160:2614–22.CrossRefPubMed Turner B, Cunningham W, Duan N. Delayed medical care after diagnosis in a US national probability sample of persons infected with human immunodeficiency virus. Arch Intern Med. 2000;160:2614–22.CrossRefPubMed
37.
go back to reference Gebo K, Fleishman J, Conviser R. Racial and Gender Disparities in Receipt of Highly Active Antiretroviral Therapy Persist in a Multistate Sample of HIV Patients in 2001. J Acquir Immune Defic Syndr. 2005;38(1):96–103.CrossRefPubMed Gebo K, Fleishman J, Conviser R. Racial and Gender Disparities in Receipt of Highly Active Antiretroviral Therapy Persist in a Multistate Sample of HIV Patients in 2001. J Acquir Immune Defic Syndr. 2005;38(1):96–103.CrossRefPubMed
39.
40.
go back to reference Losina E, Schackman B, Sadownik S. Racial and gender disparities in life expectancy losses among HIV-infected persons in the United States: impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy. Clin Infect Dis. 2009;49(10):1570–8.CrossRefPubMedPubMedCentral Losina E, Schackman B, Sadownik S. Racial and gender disparities in life expectancy losses among HIV-infected persons in the United States: impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy. Clin Infect Dis. 2009;49(10):1570–8.CrossRefPubMedPubMedCentral
41.
go back to reference Haines C, Fleishman J, Yehia B. Closing the gap in antiretroviral initiation and viral suppression: time trends and racial disparities. J Acquir Immune Defic Syndr. 2016;73(3):340–7.CrossRefPubMed Haines C, Fleishman J, Yehia B. Closing the gap in antiretroviral initiation and viral suppression: time trends and racial disparities. J Acquir Immune Defic Syndr. 2016;73(3):340–7.CrossRefPubMed
42.
go back to reference McManus K, Rhodes A, Bailey S. Affordable care act qualified health plan coverage: association with improved HIV viral suppression for AIDS drug assistance program clients in a medicaid nonexpansion state. CID. 2016;63(3):396–403.CrossRef McManus K, Rhodes A, Bailey S. Affordable care act qualified health plan coverage: association with improved HIV viral suppression for AIDS drug assistance program clients in a medicaid nonexpansion state. CID. 2016;63(3):396–403.CrossRef
43.
go back to reference Hoyo-Ulloa I, Belaunzarán-Zamudio PF, Crabtree-Ramirez B, Galindo-Fraga A, Pérez-Aguinaga ME, Sierra-Madero JG. Impact of the immune reconstitution inflammatory syndrome (IRIS) on mortality and morbidity in HIV-infected patients in Mexico. Int J Infect Dis. 2011;15(6):e408–14.CrossRefPubMedPubMedCentral Hoyo-Ulloa I, Belaunzarán-Zamudio PF, Crabtree-Ramirez B, Galindo-Fraga A, Pérez-Aguinaga ME, Sierra-Madero JG. Impact of the immune reconstitution inflammatory syndrome (IRIS) on mortality and morbidity in HIV-infected patients in Mexico. Int J Infect Dis. 2011;15(6):e408–14.CrossRefPubMedPubMedCentral
44.
go back to reference Bicanic T, Meintjes G, Rebe K. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr. 2009;51(2):130–4.CrossRefPubMed Bicanic T, Meintjes G, Rebe K. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr. 2009;51(2):130–4.CrossRefPubMed
45.
go back to reference Kambugu A, Meya DB, Rhein J. Outcomes of cryptococcal meningitis in Uganda before and after the availability of high active antiretroviral therapy. CID. 2008;46(11):1694–701.CrossRef Kambugu A, Meya DB, Rhein J. Outcomes of cryptococcal meningitis in Uganda before and after the availability of high active antiretroviral therapy. CID. 2008;46(11):1694–701.CrossRef
46.
go back to reference Crum-Cianfone N, Grandits G, Echols S. Trends and causes of hospitalizations among HIV-infected persons during the late HAART Era: what is the impact of CD4 Counts and HAART use? J Acquir Immune Defic Syndr. 2010;54(3):248–57.CrossRef Crum-Cianfone N, Grandits G, Echols S. Trends and causes of hospitalizations among HIV-infected persons during the late HAART Era: what is the impact of CD4 Counts and HAART use? J Acquir Immune Defic Syndr. 2010;54(3):248–57.CrossRef
47.
go back to reference Crowell T, Gebo K, Blankson J. Hospitalization rates and reasons among HIV elite controllers and persons with medically controlled HIV infection. J Infect Dis. 2015;211(11):1692–702.CrossRefPubMed Crowell T, Gebo K, Blankson J. Hospitalization rates and reasons among HIV elite controllers and persons with medically controlled HIV infection. J Infect Dis. 2015;211(11):1692–702.CrossRefPubMed
50.
go back to reference Bachhuber M, Southern W. Hospitalization rates of people living with HIV in the United States, 2009. Public Health Rep. 2014;129(2):178–86.PubMedPubMedCentral Bachhuber M, Southern W. Hospitalization rates of people living with HIV in the United States, 2009. Public Health Rep. 2014;129(2):178–86.PubMedPubMedCentral
Metadata
Title
Hospital days attributable to immune reconstitution inflammatory syndrome in persons living with HIV before and after the 2012 DHHS HIV guidelines
Authors
Peter Liu
Rebecca Dillingham
Kathleen A. McManus
Publication date
01-12-2017
Publisher
BioMed Central
Published in
AIDS Research and Therapy / Issue 1/2017
Electronic ISSN: 1742-6405
DOI
https://doi.org/10.1186/s12981-017-0152-0

Other articles of this Issue 1/2017

AIDS Research and Therapy 1/2017 Go to the issue