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Lower CD4 Count Linked to Non-AIDS Cancers in EuroSIDA Study
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16th Conference on Retroviruses and Opportunistic Infections,
February 8-11, 2009, Montreal
Mark Mascolini
From Jules: HIV is the culprit. HIV accelerates aging of the immune system; a recent study in JAIDS and on the NATAP website found HIV accelerates a change in naive & memory CD4 to the type in older people. This change facilitates the onset of comorbidities as the immune system ages including neurologic complications, kidney disease, bone disease, and cardiovascular diisease. We must address this aspect of HIV..
Every doubling of a person's CD4 count independently lowered the incidence of a non-AIDS cancer 11% in a study of 12,865 EuroSIDA cohort member [1]. The finding confirms results of a recent meta-analysis tying immunodeficiency to non-AIDS cancers in people with HIV and transplant patients [2]. The EuroSIDA investigators established the correlation between CD4 count and anal cancer, digestive organ cancers, lung cancer, hematologic cancers, and urinary and genital cancers.
The study involved 12,865 HIV-infected people with a CD4 count measured before enrollment in EuroSIDA and with follow-up after enrollment, including CD4 count, viral load, and antiretroviral treatment status within 6 months of any non-AIDS cancer diagnosis. The model used to determine factors related to non-AIDS cancer diagnosis adjusted for year of follow-up, gender, HIV exposure group, race, region of Europe, time on combination antiretroviral therapy, hepatitis B and C status, nadir CD4 count, and whether the patient ever smoked.
The EuroSIDA team recorded 317 non-AIDS malignancies in 309 people during 75,234 person-years of follow-up for an incidence of 4.2 cancers per 1000 person-years (95% confidence interval 3.7 to 4.7). Non-AIDS cancers were significantly more likely in men (P = 0.01), older people (P < 0.0001), people with a lower CD4 count (P = 0.0001), people with a prior non-AIDS cancer diagnosis (P = 0.01), and people who enrolled in EuroSIDA in an earlier year (P < 0.001). The researchers estimated that 24% of people with a non-AIDS malignancy died within 12 months of the diagnosis, and 40% died within 24 months.
After adjustment for the variables noted above, incidence of non-AIDS cancers from 1994 through 2007 fell from 6 per 1000 person-years with a CD4 count below 200, to about 5 per 1000 person-years for a count of 201 to 350, and to about 3 per 1000 person-years with more than 350 CD4s. Every two times higher CD4 count meant an 11% lower incidence of a non-AIDS malignancy (P = 0.01). Five other factors independently raised the risk of a non-AIDS cancer diagnosis:
• Prior AIDS: P = 0.002
• Prior non-AIDS cancer: P = 0.001
• Hepatitis B: P < 0.0001
• Older age: P < 0.0001
• Time on combination antiretroviral therapy: P < 0.0001
People infected with HIV heterosexually had a lower incidence of non-AIDS cancer than people infected during sex between men (P = 0.02). And nonwhites had a lower incidence than whites (P = 0.01).
Every CD4 count doubling correlated significantly with a lower incidence of anal cancer (P = 0.02) and digestive cancers (P = 0.003). This correlation fell short of significance in independent analyses of lung cancers, hematologic cancers, and urinary and genital cancers because of the small number of these cancers diagnosed. Only "other" non-AIDS cancers did not follow this trend.
The EuroSIDA investigators suggested that a possible explanation for the higher non-AIDS cancer risk with lower CD4 counts is "enhanced oncogenic potential of pro-oncogenic viruses," such as human papillomavirus. Because antiretroviral therapy boosts CD4 counts, they proposed that "HIV is a suitable candidate model for improving our understanding of how immunosuppression affects oncogenic transformation."
References
1. Reekie J, Mocroft A, Engsis F, et al. Relationship between current level of immunodeficiency and non-AIDS defining malignancies. 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal. Abstract 860a.
2. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370:59-67.
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