Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa
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 I...
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| Veröffentlicht in: | PloS one 2012-11, Vol.7 (11), p.e40623 |
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| description | 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.
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. 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. |
| doi_str_mv | 10.1371/journal.pone.0040623 |
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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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0040623</identifier><identifier>PMID: 23152745</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adult ; Adults ; AIDS ; AIDS-Related Opportunistic Infections ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; Antiretroviral Therapy, Highly Active - adverse effects ; Biology ; C-reactive protein ; CD4 Lymphocyte Count ; Confidence intervals ; Cryptococcosis ; Development and progression ; Fatalities ; Female ; Fertility clinics ; Folliculitis ; Follow-Up Studies ; Fungal infections ; Health aspects ; Health care ; Health risks ; Hemoglobin ; Herpes zoster ; Highly active antiretroviral therapy ; HIV ; HIV Infections - complications ; HIV Infections - drug therapy ; Human immunodeficiency virus ; Humans ; Immune reconstitution ; Immune Reconstitution Inflammatory Syndrome - epidemiology ; Immune Reconstitution Inflammatory Syndrome - etiology ; Immune Reconstitution Inflammatory Syndrome - mortality ; Immunodeficiency ; Incidence ; Infection ; Inflammation ; Kaposis sarcoma ; Lymphadenopathy ; Male ; Medical personnel ; Medicine ; Morbidity ; Mortality ; Mycoses ; Opportunist infection ; Optimization ; Patients ; Risk analysis ; Risk Factors ; South Africa - epidemiology ; Therapy ; Tuberculosis ; Ulcers ; Viral Load ; Warts</subject><ispartof>PloS one, 2012-11, Vol.7 (11), p.e40623</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Haddow et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Haddow et al 2012 Haddow et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-50be7ca6bddf074a08af22ab24204812a92b3c1a2ba0c6761ac7ac22ccfa784e3</citedby><cites>FETCH-LOGICAL-c758t-50be7ca6bddf074a08af22ab24204812a92b3c1a2ba0c6761ac7ac22ccfa784e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495974/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495974/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,2932,23875,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23152745$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ahuja, Sunil K.</contributor><creatorcontrib>Haddow, Lewis John</creatorcontrib><creatorcontrib>Moosa, Mahomed-Yunus Suleman</creatorcontrib><creatorcontrib>Mosam, Anisa</creatorcontrib><creatorcontrib>Moodley, Pravi</creatorcontrib><creatorcontrib>Parboosing, Raveen</creatorcontrib><creatorcontrib>Easterbrook, Philippa Jane</creatorcontrib><title>Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adult</subject><subject>Adults</subject><subject>AIDS</subject><subject>AIDS-Related Opportunistic Infections</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Antiretroviral Therapy, Highly Active - adverse effects</subject><subject>Biology</subject><subject>C-reactive protein</subject><subject>CD4 Lymphocyte Count</subject><subject>Confidence intervals</subject><subject>Cryptococcosis</subject><subject>Development and progression</subject><subject>Fatalities</subject><subject>Female</subject><subject>Fertility clinics</subject><subject>Folliculitis</subject><subject>Follow-Up Studies</subject><subject>Fungal infections</subject><subject>Health aspects</subject><subject>Health care</subject><subject>Health risks</subject><subject>Hemoglobin</subject><subject>Herpes zoster</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immune reconstitution</subject><subject>Immune Reconstitution Inflammatory Syndrome - epidemiology</subject><subject>Immune Reconstitution Inflammatory Syndrome - etiology</subject><subject>Immune Reconstitution Inflammatory Syndrome - mortality</subject><subject>Immunodeficiency</subject><subject>Incidence</subject><subject>Infection</subject><subject>Inflammation</subject><subject>Kaposis sarcoma</subject><subject>Lymphadenopathy</subject><subject>Male</subject><subject>Medical personnel</subject><subject>Medicine</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Mycoses</subject><subject>Opportunist infection</subject><subject>Optimization</subject><subject>Patients</subject><subject>Risk analysis</subject><subject>Risk Factors</subject><subject>South Africa - epidemiology</subject><subject>Therapy</subject><subject>Tuberculosis</subject><subject>Ulcers</subject><subject>Viral 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Africa</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-11-12</date><risdate>2012</risdate><volume>7</volume><issue>11</issue><spage>e40623</spage><pages>e40623-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23152745</pmid><doi>10.1371/journal.pone.0040623</doi><tpages>e40623</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-11, Vol.7 (11), p.e40623 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1970682161 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acquired immune deficiency syndrome Adult Adults AIDS AIDS-Related Opportunistic Infections Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Antiretroviral Therapy, Highly Active - adverse effects Biology C-reactive protein CD4 Lymphocyte Count Confidence intervals Cryptococcosis Development and progression Fatalities Female Fertility clinics Folliculitis Follow-Up Studies Fungal infections Health aspects Health care Health risks Hemoglobin Herpes zoster Highly active antiretroviral therapy HIV HIV Infections - complications HIV Infections - drug therapy Human immunodeficiency virus Humans Immune reconstitution Immune Reconstitution Inflammatory Syndrome - epidemiology Immune Reconstitution Inflammatory Syndrome - etiology Immune Reconstitution Inflammatory Syndrome - mortality Immunodeficiency Incidence Infection Inflammation Kaposis sarcoma Lymphadenopathy Male Medical personnel Medicine Morbidity Mortality Mycoses Opportunist infection Optimization Patients Risk analysis Risk Factors South Africa - epidemiology Therapy Tuberculosis Ulcers Viral Load Warts |
| title | Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa |
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