title: Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma: higher incidence and mortality in Africa than in the UK.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain. emili.letang@cresib.cat
authors: Emilio
authors: E
authors: Letang
authors: James J
authors: JJ
authors: Lewis
authors: Mark
authors: M
authors: Bower
authors: Anisa
authors: A
authors: Mosam
authors: Margareth
authors: M
authors: Borok
authors: Thomas B
authors: TB
authors: Campbell
authors: Denise
authors: D
authors: Naniche
authors: Tom
authors: T
authors: Newsom-Davis
authors: Fahmida
authors: F
authors: Shaik
authors: Suzanne
authors: S
authors: Fiorillo
authors: Jose M
authors: JM
authors: Miro
authors: David
authors: D
authors: Schellenberg
authors: Philippa J
authors: PJ
authors: Easterbrook
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D019288:Herpesvirus 8, Human / Q000302:isolation & purification; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000453:epidemiology* / Q000401:mortality / Q000821:virology; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D012514:Sarcoma, Kaposi / Q000453:epidemiology* / Q000401:mortality / Q000821:virology; D006113:United Kingdom / Q000453:epidemiology; D019562:Viral Load
chemical_list: D004279:DNA, Viral