Incidence, Clinical Spectrum, Risk Factors and Impact of HIV-Associated Immune Reconstitution Inflammatory Syndrome in South Africa
Identifieur interne : 001A38 ( Ncbi/Curation ); précédent : 001A37; suivant : 001A39Incidence, Clinical Spectrum, Risk Factors and Impact of HIV-Associated Immune Reconstitution Inflammatory Syndrome in South Africa
Auteurs : Lewis John Haddow [Royaume-Uni, Afrique du Sud] ; Mahomed-Yunus Suleman Moosa [Afrique du Sud] ; Anisa Mosam [Afrique du Sud] ; Pravi Moodley [Afrique du Sud] ; Raveen Parboosing [Afrique du Sud] ; Philippa Jane Easterbrook [Afrique du Sud]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
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 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.
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.
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DOI: 10.1371/journal.pone.0040623
PubMed: 23152745
PubMed Central: 3495974
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Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Infectious Diseases, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban</wicri:regionArea><wicri:noRegion>Durban</wicri:noRegion></affiliation></author><author><name sortKey="Moosa, Mahomed Yunus Suleman" sort="Moosa, Mahomed Yunus Suleman" uniqKey="Moosa M" first="Mahomed-Yunus Suleman" last="Moosa">Mahomed-Yunus Suleman Moosa</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Infectious Diseases, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Infectious Diseases, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban</wicri:regionArea><wicri:noRegion>Durban</wicri:noRegion></affiliation></author><author><name sortKey="Mosam, Anisa" sort="Mosam, Anisa" uniqKey="Mosam A" first="Anisa" last="Mosam">Anisa Mosam</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Dermatology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Dermatology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban</wicri:regionArea><wicri:noRegion>Durban</wicri:noRegion></affiliation></author><author><name sortKey="Moodley, Pravi" sort="Moodley, Pravi" uniqKey="Moodley P" first="Pravi" last="Moodley">Pravi Moodley</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Virology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Virology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban</wicri:regionArea><wicri:noRegion>Durban</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>National Health Laboratory Services, Inkosi Albert Luthuli Central Hospital, Durban, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>National Health Laboratory Services, Inkosi Albert Luthuli Central Hospital, Durban</wicri:regionArea><wicri:noRegion>Durban</wicri:noRegion></affiliation></author><author><name sortKey="Parboosing, Raveen" sort="Parboosing, Raveen" uniqKey="Parboosing R" first="Raveen" last="Parboosing">Raveen Parboosing</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Virology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Virology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban</wicri:regionArea><wicri:noRegion>Durban</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>National Health Laboratory Services, Inkosi Albert Luthuli Central Hospital, Durban, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>National Health Laboratory Services, Inkosi Albert Luthuli Central Hospital, Durban</wicri:regionArea><wicri:noRegion>Durban</wicri:noRegion></affiliation></author><author><name sortKey="Easterbrook, Philippa Jane" sort="Easterbrook, Philippa Jane" uniqKey="Easterbrook P" first="Philippa Jane" last="Easterbrook">Philippa Jane Easterbrook</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Infectious Diseases, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa</addr-line></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Infectious Diseases, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban</wicri:regionArea><wicri:noRegion>Durban</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>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.</p></sec><sec><title>Methods and Findings</title><p>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<sub>10</sub> (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.</p></sec><sec><title>Conclusion</title><p>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.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Murdoch, Dm" uniqKey="Murdoch D">DM Murdoch</name></author><author><name sortKey="Venter, Wdf" uniqKey="Venter W">WDF Venter</name></author><author><name sortKey="Feldmann, C" uniqKey="Feldmann C">C Feldmann</name></author><author><name sortKey="Van Rie, A" uniqKey="Van Rie A">A Van Rie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ratnam, I" uniqKey="Ratnam I">I Ratnam</name></author><author><name sortKey="Chiu, C" uniqKey="Chiu C">C 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