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Multicohort Study Confirms Continuing Hodgkin Lymphoma Risk With HAART
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12th European AIDS Conference, November 11-13, 2009, Cologne, Germany
Mark Mascolini
Highly active antiretroviral therapy (HAART) had no discernible impact on new diagnoses (incidence) of Hodgkin lymphoma in people with HIV, according to results of a pan-European study combining data from 16 cohorts [1]. The result confirms previous studies indicating that potent antiretroviral therapy has not always helped people with HIV evade this non-AIDS cancer, though a recent Australian study charted a decline in Hodgkin lymphoma after the early HAART era (1996-1999) [2].
This large European study suggested a possible clue to Hodgkin lymphoma in HIV-infected people: a sudden dwindling of CD4 cells despite otherwise successful antiretroviral therapy.
COHERE cohort collaborators analyzed data on 40,168 adults who had never taken an antiretroviral when they entered the cohort, then began therapy after January 1, 1996. To distinguish potential differences between antiretroviral-treated people with and without newly diagnosed Hodgkin lymphoma, the researcher also designed a case-control study. The "cases" were people without AIDS and taking antiretrovirals when Hodgkin lymphoma was diagnosed. The researchers matched each case to several "controls" by original cohort, age, gender, HIV transmission risk group, CD4 count at the start of therapy, and viral load at lymphoma diagnosis in cases or at the same length of follow-up since starting antiretrovirals in controls.
During 159,133 person-years of follow-up, clinicians diagnosed Hodgkin lymphoma in 78 people to yield an incidence of 50.4 cases per 100,000 person-years in 17 people in whom lymphoma developed before they started antiretrovirals and 48.7 per 100,000 person-years in 61 people diagnosed with lymphoma after they started HAART. Thus incidence was nearly the same before and after Europeans started taking potent regimens. Age, gender, HIV disease stage, and viral load at cohort entry did not influence the risk of lymphoma. Nor did initial CD4 count above or below 200 affect lymphoma risk.
The investigators continued to track people after diagnosis of Hodgkin lymphoma. During a median follow-up of 18 months (interquartile range 4.8 to 34.8), 12 of 78 people with lymphoma (15%) died. Six of the 12 died within 6 months of diagnosis. Survival with lymphoma stood at 88% 1 year after diagnosis and at 81% after 2 years.
The COHERE team matched 18 of the "cases" with lymphoma to 79 "controls" without lymphoma. Sixteen of 18 cases had an HIV load below 50 copies at lymphoma diagnosis. Median CD4 count at diagnosis stood at 195, compared with a median of 369 CD4s in controls. That finding supports other evidence suggesting that more highly immunocompromised people run a greater risk of Hodgkin lymphoma (and some other non-AIDS cancers) [3].
CD4 counts had been climbing by a median of 60.2 cells yearly in cases, until the year before lymphoma diagnosis, when the median CD4 count fell by 98.6 cells. CD4 counts in controls did not undergo this turnaround, climbing steadily at a rate of 57.4 per year. CD4-cell slopes differed significantly between cases and controls in the year before lymphoma diagnosis (P = 0.003) but not before that.
The investigators proposed that people whose CD4 count begins a sudden slide during otherwise successful antiretroviral therapy should be evaluated for Hodgkin lymphoma.
References
1. Bohlius J, Lymphoma Working Group of COHERE. HIV-related Hodgkin lymphoma in the era of HAART: incidence and survival in a European multi-cohort study: preliminary results. 12th European AIDS Conference. November 11-13, 2009. Cologne, Germany. Abstract BPD1/1.
2. van Leeuwen MT, Vajdic CM, Middleton MG, et al. Continuing declines in some but not all HIV-associated cancers in Australia after widespread use of antiretroviral therapy. AIDS. 2009;23:2183-2190.
3. Bedimo RJ, McGinnis KA, Dunlap M, Rodriguez-Barradas MC, Justice AC. Incidence of non-AIDS-defining malignancies in HIV-infected versus noninfected patients in the HAART era: impact of immunosuppression. J Acquir Immune Defic Syndr. 2009 Jul 16. Epub ahead of print.
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