title: Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa.
abstract: BACKGROUND
  Immune 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.
  
  
  RESULTS
  498 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 log(10) (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.
  
  
  CONCLUSIONS
  IRIS 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.
authors.affiliation: Centre for Sexual Health and HIV Research, Research Department of Infection and Population Health, University College London, London, United Kingdom.
authors.forename: Lewis John
authors.initials: LJ
authors.lastname: Haddow
authors.forename: Mahomed-Yunus Suleman
authors.initials: MY
authors.lastname: Moosa
authors.forename: Anisa
authors.initials: A
authors.lastname: Mosam
authors.forename: Pravi
authors.initials: P
authors.lastname: Moodley
authors.forename: Raveen
authors.initials: R
authors.lastname: Parboosing
authors.forename: Philippa Jane
authors.initials: PJ
authors.lastname: Easterbrook
mesh_terms: D017088:AIDS-Related Opportunistic Infections; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality; D015994:Incidence; D008297:Male; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D019562:Viral Load