Annals of Oncology Advance Access published online on January 29, 2009
Annals of Oncology, doi:10.1093/annonc/mdn697
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman's disease
1 Department of Medical oncology, Barts and the London Medical School
2 Department of Oncology, Imperial College School of Medicine, London, UK
* Correspondence to: Dr J. Stebbing, Department of Oncology, Imperial College School of Medicine, The Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK. Tel: +44-208-237-5054; Fax: +44-208-746-8863; E-mail: j.stebbing{at}imperial.ac.uk
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/mm3, 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.
HHV-8, Highly active antiretroviral therapy, HIV, Kaposi's sarcoma, multicentric Castleman's disease
Received for publication September 24, 2008. Accepted for publication October 2, 2008.