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To the Editor—We read with interest the article by Achenbach et al [1] on paradoxical immune reconstitution inflammatory syndrome (IRIS) but are left with some concerns regarding the high incidence and mortality of Kaposi sarcoma–associated IRIS (KS-IRIS).

Bower et al [2] first reported the incidence of KS-IRIS in a prospective cohort of 150 naive human immunodeficiency virus (HIV)–infected patients with KS beginning antiretroviral therapy (ART) in London, United Kingdom. Ten of 150 patients (7%) developed KS-IRIS. In a more recent prospective study from Mozambique, 4 of 13 patients (31%) with pre-ART KS developed KS-IRIS [3], an incidence resembling that reported by Achenbach et al. However, we believe there may be substantial differences between Africa and well-resourced settings and that the case definition may account for interstudy variations. To test this hypothesis, we adopted a standardized KS-IRIS definition (Table 1) and conducted a multisite study, including 417 ART-naive HIV-infected patients with KS from 3 African and 1 European cohort [4]. In total, 40 of 204 patients (20%) in Africa and 18 of 213 (8%) in the European cohort developed KS-IRIS. Among the possible explanations for these differences is the later presentation in Africa, with lower CD4 cell counts, higher proportion of detectable KS-associated herpesvirus (KSHV) DNA in plasma, more advanced KS stage, and lower use of chemotherapy as initial treatment for KS, all factors associated with unfavorable KS outcomes [5–7]. In the study by Achenbach et al [1], almost a third of patients with KS developed KS-IRIS after ART initiation, a substantially greater incidence than in previous reports from Europe [2]. We wonder whether this difference could be due to specific characteristics of this study population.

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