The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman's disease

Background: In HIV cohorts with access to highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) is falling; however, the incidence of multicentric Castleman's disease (MCD) in HIV has not previously been described. Methods: The incidence of HIV-associated MCD was calculated from a prospective HIV database with 56 202 patient-years of follow-up and compared with KS. Univariate and multivariate analyses were carried out to identify factors associated with MCD. Plasma human herpesvirus (HHV)-8 DNA levels were measured in HIV-seropositive individuals with newly diagnosed MCD (n = 24), KS (n = 72), HIV-associated lymphoma (n = 74) and HIV-positive controls (n = 53). Results: From 24 cases of HIV-associated MCD, the incidence measured 4.3/10 000 patient-years [95% confidence interval (CI) 2.7-6.4]. The incidence in the pre-HAART (1983-1996), early-HAART (1997-2001) and later HAART (2002-2007) eras were 2.3 (95% CI 0.02-4.2), 2.8 (95% CI 0.9-6.5) and 8.3 (95% CI 4.6-12.6), respectively, representing a statistically significant increase over time (P < 0.05). In contrast, from 1180 cases of KS, the incidence in this cohort decreased with time. Multivariate analysis demonstrated that a nadir CD4 count > 200/mm(3), increased age, no previous HAART exposure and non-Caucasian ethnicity were all associated with an increased risk of MCD. Plasma HHV-8 DNA levels were higher in patients with newly diagnosed MCD than with KS, lymphomas or HIV-positive controls (Mann-Whitney U-test, P < 0.0001). Conclusions: The incidence of HIV-associated MCD is increasing. It appears to occur more frequently in older HIV-positive individuals with well-preserved immune function.