Immune reconstitution inflammatory syndrome associated with kaposi sarcoma: higher incidence and mortality in Africa than in the UK.


Letang, E; Lewis, JJ; Bower, M; Mosam, A; Borok, M; Campbell, TB; Naniche, D; Newsom-Davis, T; Shaik, F; Fiorillo, S; Miro, JM; Schellenberg, D; Easterbrook, PJ; (2013) Immune reconstitution inflammatory syndrome associated with kaposi sarcoma: higher incidence and mortality in Africa than in the UK. AIDS (London, England), 27 (10). pp. 1603-13. ISSN 0269-9370 DOI: https://doi.org/10.1097/QAD.0b013e328360a5a1

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Abstract

OBJECTIVES: To assess the incidence, predictors, and outcomes of Kaposi sarcoma-associated paradoxical immune reconstitution inflammatory syndrome (KS-IRIS) in antiretroviral therapy (ART)-naive HIV-infected patients with Kaposi sarcoma initiating ART in both well resourced and limited-resourced settings.<br/> DESIGN: Pooled analysis of three prospective cohorts of ART-naive HIV-infected patients with Kaposi sarcoma from sub-Saharan Africa (SSA) and one from the UK.<br/> METHODS: KS-IRIS case definition was standardized across sites. Cox regression and Kaplan-Meier survival analysis were used to identify the incidence and predictors of KS-IRIS and Kaposi sarcoma-associated mortality.<br/> RESULTS: Fifty-eight of 417 (13.9%) eligible individuals experienced KS-IRIS with an incidence 2.5 times higher in the African vs. European cohorts (P=0.001). ART alone as initial Kaposi sarcoma treatment (hazard ratio 2.97, 95% confidence interval (CI) 1.02-8.69); T1 Kaposi sarcoma stage (hazard ratio 2.96, 95% CI 1.26-6.94); and plasma HIV-1 RNA more than 5 log₁₀ copies/ml (hazard ratio 2.14, 95% CI 1.25-3.67) independently predicted KS-IRIS at baseline. Detectable plasma Kaposi sarcoma-associated herpes virus (KSHV) DNA additionally predicted KS-IRIS among the 259 patients with KSHV DNA assessed (hazard ratio 2.98, 95% CI 1.23-7.19). Nineteen KS-IRIS patients died, all in SSA. Kaposi sarcoma mortality was 3.3-fold higher in Africa, and was predicted by KS-IRIS (hazard ratio 19.24, CI 7.62-48.58), lack of chemotherapy (hazard ratio 2.35, 95% CI 1.09-5.05), pre-ART CD4 cell count less than 200 cells/μl (hazard ratio 2.04, 95% CI 0.99-4.2), and detectable baseline KSHV DNA (hazard ratio 2.12, 95% CI 0.94-4.77).<br/> CONCLUSION: KS-IRIS incidence and mortality are higher in SSA than in the UK. This is largely explained by the more advanced Kaposi sarcoma disease and lower chemotherapy availability. KS-IRIS is a major contributor to Kaposi sarcoma-associated mortality in Africa. Our results support the need to increase awareness on KS-IRIS, encourage earlier presentation, referral and diagnosis of Kaposi sarcoma, and advocate on access to systemic chemotherapy in Africa.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Centre for Evaluation
Centre for Maternal, Reproductive and Child Health (MARCH)
Tropical Epidemiology Group
PubMed ID: 23462220
Web of Science ID: 326840700009
URI: http://researchonline.lshtm.ac.uk/id/eprint/639137

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