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

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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.