Abstract
BackgroundImmune reconstitution inflammatory syndrome (IRIS) is a widely recognised complication of antiretroviral therapy (ART), but there are still limited data from resource-limited settings. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa.Methods and Findings498 adults initiating ART in Durban, South Africa were followed prospectively for 24 weeks. IRIS diagnosis was based on consensus expert opinion, and classified by mode of presentation (paradoxical worsening of known opportunistic infection [OI] or unmasking of subclinical disease). 114 patients (22.9%) developed IRIS (36% paradoxical, 64% unmasking). Mucocutaneous conditions accounted for 68% of IRIS events, mainly folliculitis, warts, genital ulcers and herpes zoster. Tuberculosis (TB) accounted for 25% of IRIS events. 18/135 (13.3%) patients with major pre-ART OIs (e.g. TB, cryptococcosis) developed paradoxical IRIS related to the same OI. Risk factors for this type of IRIS were baseline viral load >5.5 vs. <4.5 log10 (adjusted hazard ratio 7.23; 95% confidence interval 1.35–38.76) and ≤30 vs. >30 days of OI treatment prior to ART (2.66; 1.16–6.09). Unmasking IRIS related to major OIs occurred in 25/498 patients (5.0%), and risk factors for this type of IRIS were baseline C-reactive protein ≥25 vs. <25 mg/L (2.77; 1.31–5.85), haemoglobin <10 vs. >12 g/dL (3.36; 1.32–8.52), ≥10% vs. <10% weight loss prior to ART (2.31; 1.05–5.11) and mediastinal lymphadenopathy on pre-ART chest x-ray (9.15; 4.10–20.42). IRIS accounted for 6/25 (24%) deaths, 13/65 (20%) hospitalizations and 10/35 (29%) ART interruptions or discontinuations.ConclusionIRIS occurred in almost one quarter of patients initiating ART, and accounted for one quarter of deaths in the first 6 months. Priority strategies to reduce IRIS-associated morbidity and mortality in ART programmes include earlier ART initiation before onset of advanced immunodeficiency, improved pre-ART screening for TB and cryptococcal infection, optimization of OI therapy prior to ART initiation, more intensive clinical monitoring in initial weeks of ART, and education of health care workers and patients about IRIS.
Highlights
Immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution disease is a widely recognised phenomenon that occurs in 10227% of patients initiating antiretroviral therapy (ART) [1,2,3,4,5,6,7,8]
Priority strategies to reduce IRIS-associated morbidity and mortality in ART programmes include earlier ART initiation before onset of advanced immunodeficiency, improved pre-ART screening for TB and cryptococcal infection, optimization of opportunistic infection (OI) therapy prior to ART initiation, more intensive clinical monitoring in initial weeks of ART, and education of health care workers and patients about IRIS
The syndrome may present in two different ways: ‘‘paradoxical’’ IRIS, when an opportunistic infection (OI) diagnosed pre-ART initially responds to treatment but deteriorates following ART initiation; or ‘‘unmasking’’ IRIS, where disease that is not clinically apparent prior to ART is triggered by ART initiation, often with unusual or florid inflammatory features [1,9] in association with rapid restoration of pathogen-specific immune responses [10]
Summary
Immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution disease is a widely recognised phenomenon that occurs in 10227% of patients initiating antiretroviral therapy (ART) [1,2,3,4,5,6,7,8]. Pathogen-related factors include shorter duration of anti-tuberculous or anti-cryptococcal therapy prior to ART initiation [13,16,28,29,30,31], extrapulmonary or disseminated TB [15,17,18,29], higher fungal burden in cryptococcosis [30,32], higher plasma KS-associated herpes virus (KSHV) load [22], and higher number of prior OIs [27]. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa
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