Epidemiology of HIV-Related Immune Reconstitution Inflammatory Syndrome in sub-Saharan Africa

Lead Research Organisation: University College London
Department Name: Infection and Population Health

Abstract

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Technical Summary

Between 10% and 40% of patients who start highly active antiretroviral therapy (HAART) experience a syndrome of an excessive inflammatory response and a paradoxical deterioration in clinical status. This phenomenon is thought to be due to a HAART-associated recovery of pathogen-specific immune responses to pre-existing or latent infections, and has been termed immune reconstitution inflammatory syndrome (IRIS). The clinical spectrum is diverse and cases of IRIS associated with more than 20 different pathogens have been described. IRIS represents a major diagnostic challenge in patients who have recently started HAART, and severe IRIS may result in organ failure, hospitalization or death.
There have been few systematic studies on the frequency, risk factors and clinical course of IRIS, and none to date undertaken in sub-Saharan Africa. It is anticipated that the problem of IRIS will be even more significant with HAART roll-out programmes in less developed countries where the underlying prevalence of infections such as Mycobacterium tuberculosis, Cryptococcus neoformans and hepatitis B is high, and patients initiating HAART are more likely to have advanced immunodeficiency. A greater understanding of the epidemiology, diagnostic criteria, clinical outcome and pathogenesis of IRIS in a sub-Saharan African setting is urgently needed to develop more effective strategies to diagnose, manage and prevent IRIS. The IRIS Collaborative Research Group represents a collaboration between the department of HIV/GUM at King‘s College, London, and the Nelson R Mandela School of Medicine, aiming to complete the first comprehensive prospective study of IRIS in Africa.
The principal aim of this study is to characterize the epidemiology of IRIS in patients starting HAART in KwaZulu-Natal. Specific objectives: (i) to determine the incidence, clinical spectrum and clinical features of IRIS, and the baseline seroprevalence of the main HIV-related infectious pathogens in patients initiang HAART; (ii) to refine the diagnostic criteria for IRIS, and identify overall and pathogen-risk factors for IRIS; (iii) to determine the clinical outcome of IRIS, particularly the contribution to early mortality after HAART initiation.
1000 HIV-1 infected adult antiretroviral-naove patients initiating HAART at three ARV roll-out clinics in the Durban area will be enrolled over six months into a prospective observational cohort study. Patients will be monitored closely for six months for the development of IRIS events. Clinical data and sample collection will coincide with the routine schedule of baseline and monthly follow-up visits. Samples will be stored for serological batch testing to identify pathogen-related risk factors for IRIS. Univariate and multivariate logistic regression analyses will be used to identify independent demographic, clinical and laboratory risk factors for IRIS.

Publications

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Haddow LJ (2009) Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

 
Description British Society for Antimicrobial Chemotherapy Research Grant
Amount £30,000 (GBP)
Organisation British Society for Antimicrobial Chemotherapy 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2007 
End 12/2008
 
Title Durban Collaborative IRIS Research Group 
Description The collaboration and set-up of the current cohort study have led to further immunopathological studies between Durban and Australia 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact As above 
 
Title Generic case definition of Immune Reconstitution Disease 
Description Two proposed case definitions for use in future epidemiological and immunopathological studies of IRIS, and in clinical trials 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2008 
Provided To Others? Yes  
Impact Publication in Clinical Infectious Diseases 
 
Description Durban IRIS Collaborative research group 
Organisation Government of South Africa
Department Department of Health
Country South Africa 
Sector Public 
PI Contribution Working in partnership with Professor Yunus Moosa, head of department of Infectious Diseases in University of KwaZulu-Natal. Dr Haddow (the primary grant holder) was based in Durban at UKZN for 2 years, with Prof Moosa as supervisor
Collaborator Contribution This is the lead department for this research groupProvided laboratory support for the HIV cohort studyProvided clinical sites for conducting cohort studiesCollaborated on a substudy of cytokine responses in cases and controls within the clinical cohortThe Network is itself a collaborative group, of which we are a part. The Network aims to foster collaboration in clinical and laboratory research on all aspects of IRIS. We have had a specific collaboration in the development of case definitions of the syndrome
Impact All publications to date are a product of combined work with the dept of ID in UKZN and some or all of the other collaborators
Start Year 2006
 
Description Durban IRIS Collaborative research group 
Organisation University of KwaZulu-Natal
Department Department of Infectious Diseases
Country South Africa 
Sector Academic/University 
PI Contribution Working in partnership with Professor Yunus Moosa, head of department of Infectious Diseases in University of KwaZulu-Natal. Dr Haddow (the primary grant holder) was based in Durban at UKZN for 2 years, with Prof Moosa as supervisor
Collaborator Contribution This is the lead department for this research groupProvided laboratory support for the HIV cohort studyProvided clinical sites for conducting cohort studiesCollaborated on a substudy of cytokine responses in cases and controls within the clinical cohortThe Network is itself a collaborative group, of which we are a part. The Network aims to foster collaboration in clinical and laboratory research on all aspects of IRIS. We have had a specific collaboration in the development of case definitions of the syndrome
Impact All publications to date are a product of combined work with the dept of ID in UKZN and some or all of the other collaborators
Start Year 2006
 
Description Durban IRIS Collaborative research group 
Organisation University of KwaZulu-Natal
Department Department of Virology
Country South Africa 
Sector Academic/University 
PI Contribution Working in partnership with Professor Yunus Moosa, head of department of Infectious Diseases in University of KwaZulu-Natal. Dr Haddow (the primary grant holder) was based in Durban at UKZN for 2 years, with Prof Moosa as supervisor
Collaborator Contribution This is the lead department for this research groupProvided laboratory support for the HIV cohort studyProvided clinical sites for conducting cohort studiesCollaborated on a substudy of cytokine responses in cases and controls within the clinical cohortThe Network is itself a collaborative group, of which we are a part. The Network aims to foster collaboration in clinical and laboratory research on all aspects of IRIS. We have had a specific collaboration in the development of case definitions of the syndrome
Impact All publications to date are a product of combined work with the dept of ID in UKZN and some or all of the other collaborators
Start Year 2006
 
Description Durban IRIS Collaborative research group 
Organisation University of Minnesota
Department International Network for the Study of HIV-Associated IRIS (INSHI)
Country United States 
Sector Academic/University 
PI Contribution Working in partnership with Professor Yunus Moosa, head of department of Infectious Diseases in University of KwaZulu-Natal. Dr Haddow (the primary grant holder) was based in Durban at UKZN for 2 years, with Prof Moosa as supervisor
Collaborator Contribution This is the lead department for this research groupProvided laboratory support for the HIV cohort studyProvided clinical sites for conducting cohort studiesCollaborated on a substudy of cytokine responses in cases and controls within the clinical cohortThe Network is itself a collaborative group, of which we are a part. The Network aims to foster collaboration in clinical and laboratory research on all aspects of IRIS. We have had a specific collaboration in the development of case definitions of the syndrome
Impact All publications to date are a product of combined work with the dept of ID in UKZN and some or all of the other collaborators
Start Year 2006
 
Description Durban IRIS Collaborative research group 
Organisation University of Oxford
Department Jenner Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Working in partnership with Professor Yunus Moosa, head of department of Infectious Diseases in University of KwaZulu-Natal. Dr Haddow (the primary grant holder) was based in Durban at UKZN for 2 years, with Prof Moosa as supervisor
Collaborator Contribution This is the lead department for this research groupProvided laboratory support for the HIV cohort studyProvided clinical sites for conducting cohort studiesCollaborated on a substudy of cytokine responses in cases and controls within the clinical cohortThe Network is itself a collaborative group, of which we are a part. The Network aims to foster collaboration in clinical and laboratory research on all aspects of IRIS. We have had a specific collaboration in the development of case definitions of the syndrome
Impact All publications to date are a product of combined work with the dept of ID in UKZN and some or all of the other collaborators
Start Year 2006
 
Description Vitamin D and TB-associated IRIS 
Organisation LRS Institute of Tuberculosis and Respiratory Diseases
Country India 
Sector Academic/University 
PI Contribution One of 3 sites contributing clinical and laboratory data. All sites participated in analysis of results and dissemination of findings.
Collaborator Contribution Developing an understanding of immunogenetics and nutritional aspects of IRIS in TB/HIV co-infected patients.See above.See above.
Impact The collaboration involves immunology, genetics and epidemiology expertise. Abstract presented at Australasian HIV/AIDS Conference 2011. (Paper submitted for publication.)
Start Year 2008
 
Description Vitamin D and TB-associated IRIS 
Organisation University of Malaya
Department Centre of Excellence for Research in AIDS (CERiA)
Country Malaysia 
Sector Academic/University 
PI Contribution One of 3 sites contributing clinical and laboratory data. All sites participated in analysis of results and dissemination of findings.
Collaborator Contribution Developing an understanding of immunogenetics and nutritional aspects of IRIS in TB/HIV co-infected patients.See above.See above.
Impact The collaboration involves immunology, genetics and epidemiology expertise. Abstract presented at Australasian HIV/AIDS Conference 2011. (Paper submitted for publication.)
Start Year 2008
 
Description Vitamin D and TB-associated IRIS 
Organisation University of Western Australia
Department School of Pathology and Laboratory Medicine
Country Australia 
Sector Academic/University 
PI Contribution One of 3 sites contributing clinical and laboratory data. All sites participated in analysis of results and dissemination of findings.
Collaborator Contribution Developing an understanding of immunogenetics and nutritional aspects of IRIS in TB/HIV co-infected patients.See above.See above.
Impact The collaboration involves immunology, genetics and epidemiology expertise. Abstract presented at Australasian HIV/AIDS Conference 2011. (Paper submitted for publication.)
Start Year 2008