Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS

Abstract

In persons with HIV/AIDS (PWHAs), Hodgkin lymphoma (HL) risk is increased. However, HL incidence in PWHAs has unexpectedly increased since highly active antiretroviral therapy (HAART) was introduced. We linked nationwide HIV/AIDS and cancer registry data from 1980 through 2002. Immunity was assessed by CD4 T-lymphocyte counts at AIDS onset. Annual HL incidence rates were calculated for 4 through 27 months after AIDS onset. During 477 368 person years (py's) of follow-up in 317 428 persons with AIDS (PWAs), 173 HL cases occurred (36.2 per 10(5) py's). Incidence was significantly higher in 1996 to 2002 than earlier. Incidence in PWAs with 150 to 199 CD4 cells/muL was 53.7 per 10(5) py's, whereas in PWAs with fewer than 50 CD4 cells/muL, it was 20.7 per 10(5) py's (P(trend) = .002). For each HL subtype, incidence decreased with declining CD4 counts, but nodular sclerosing decreased more precipitously than mixed cellularity, thereby increasing the proportion of mixed cellularity HL seen in PWAs. We conclude that HL incidence is lower with severe immunosuppression than with moderate immunosuppression, and HAART-related improvements in CD4 counts likely explain the increasing HL incidence in PWHAS observed since 1996. With more severe immunosuppression, nodular sclerosing HL becomes infrequent, explaining the higher proportion of mixed cellularity HL found in PWAs. Pathogenesis implications are discussed.

Figure 1.

Incidence of HL and NHL by CD4 count at AIDS onset. (A) HL compared to NHL on the same scale. (B) Comparison of linear with quadratic model for HL. Linear models fit the observed data well and showed significant trends with CD4 counts (P = .002 for HL; P < .001 for NHL). A model including a quadratic term fit the HL data better than a linear model alone (P = .053).

Figure 2.

Incidence rates and proportional distribution of HL subtypes by CD4 count at onset of AIDS. (A) Incidence rates of all HL and subtypes. (B) Proportion distribution including those not otherwise specified (NOS). NS indicates nodular sclerosing; MC, mixed cellularity; LD, lymphocyte depleted. 3 HLs with old histology classifications were not included in subtype analyses but were included in the All HL analysis because they had CD4 counts in the AIDS onset period (1 with 150-199 and 2 with ≥ 200 cells/μL).

Figure 3.

Medians and interquartile distributions of CD4 counts 0 to 12 months before lymphoma onset for Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) in all PWHAs. CD4 counts are expressed as cells/μL. n = 311 for HL cases; n = 4344 for NHL cases. NS indicates nodular sclerosing (n = 58); MC, mixed cellularity (n = 117); LD, lymphocyte depleted (n = 19); NOS, not otherwise specified (n = 113).