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Two to Three Times Higher Hodgkin Risk in First Months of ART
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XVIII International AIDS Conference, July 18-23, 2010, Vienna
Mark Mascolini
Risk of Hodgkin lymphoma, a non-AIDS cancer, was 2 to 3 times higher people in their first 2 months of antiretroviral therapy (ART) than in people not taking antiretrovirals after 1996, according to results from the French Hospital Database on HIV [1]. Low CD4 count when treatment began largely explained the correlation between early ART and Hodgkin lymphoma.
French researchers undertook this study because earlier work charted climbing incidence (new diagnosis rate) of Hodgkin lymphoma during the combination ART era. Some investigators suggest that lymphoma diagnosed during the first months of therapy may represent an immune reconstitution inflammatory syndrome (IRIS). For example, research at the US National Cancer Institute found evidence that "HAART-related improvements in CD4 counts likely explain the increasing Hodgkin lymphoma incidence in people with HIV and AIDS observed since 1996" [2].
The French study focused on HIV-infected people with no history of Hodgkin lymphoma at their first cohort visit. All were antiretroviral naive if they began combination ART during follow-up. Variables in a statistical model to determine risk factors for lymphoma diagnosis were duration of combination ART, period of follow-up, age, gender, HIV exposure group, migration from sub-Saharan Africa, AIDS stage, CD4 count, and viral load.
French Hospital Database investigators recorded 187 newly diagnosed cases of Hodgkin lymphoma in 64,386 people during 286,086 person-years of follow-up. Lymphoma incidence was statistically equivalent in the three periods analyzed: 7.9 per 10,000 person-years before 1996, 6.0 in 1996-1999, and 6.4 in 2000-2007 (P = 0.55). But an analysis adjusted for age, gender, HIV exposure group, migration from sub-Saharan Africa, AIDS stage, and combination ART duration determined that relative risk (RR) of lymphoma was higher at lower CD4 counts:
-- 0-49 CD4s: RR 5.5
-- 50-99 CD4s: RR 9.9
-- 100-199 CD4s: RR 6.7
-- 200-349 CD4s: RR 4.2
-- 350-499 CD4s: RR 2.2
-- 500 or more CD4s: RR 1.0
Early combination ART also raised the risk of Hodgkin lymphoma. In an unadjusted analysis, lymphoma risk was 3.0 times higher in treatment month 1 than in all people untreated in 1996 and later. In an analysis adjusted for the factors described for the CD4 analysis, lymphoma risk was 2.6 times higher in month 2 than in the untreated comparison group. People in the third month of combination ART had a 1.4 times higher risk of lymphoma than the comparison group, but this heightened risk lacked statistical significance because the confidence interval crossed 1.0.
The French team concluded that HIV-infected people run a higher risk of Hodgkin lymphoma in the first months of combination ART. But the investigators believe the correlations between low CD4 count and Hodgkin risk largely explain the higher risk in the first months of therapy. People beginning therapy with 50 to 99 CD4s appeared to run the highest risk of Hodgkin lymphoma.
References
1.Lanoy E, Rozenberg PS, Fily F, et al. Risk of HIV-associated Hodgkin lymphoma during the first months after initiation of combination antiretroviral therapy. XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract TUPE0159.
2. Biggar RJ, Jaffe ES, Goedert JJ, Chaturvedi A, Pfeiffer R, Engels EA. Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS. Blood. 2006;108:3786-3791.
http://bloodjournal.hematologylibrary.org/cgi/content/full/108/12/3786
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