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Failure to Respond to HBV Vaccine Linked to Higher Cancer Risk With HIV
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
Failure to respond to the hepatitis B virus (HBV) vaccine raised the risk of cancer in a case-control study, regardless of CD4 count and age [1]. That finding led Case Western Reserve University researchers to conclude that "subclinical impairment of immune surveillance may contribute to the heightened risk of cancer in HIV-infected patients."
Citing conflicting data on whether nadir or first CD4 count points to a higher risk of non-AIDS cancers [2-4], the Case Western group suggested that CD4 count alone may not be good enough to predict malignancy in people with HIV. Therefore Stephen Dando, Trevor Crowell, and colleagues evaluated HBV vaccine response as a marker of immune vigor in people with HIV.
The study involved 96 HIV-infected people with cancer in the database of the Center for AIDS Research at Case Western Reverse University in Cleveland, Ohio. Dando and Crowell excluded people without a known date of cancer diagnosis and people with a cancer diagnosis before their first Case Western visit. The investigators compared these people (the "cases") to 1482 "controls" without cancer but of similar gender, race, and HIV transmission risk category. The cases were significantly older than controls at their initial visit (average 42 versus 37 years, P < 0.001), and cases had a lower nadir CD4 count (P = 0.039). A bigger proportion of cases than controls were positive for HBV surface antigen (HBsAg), though this difference fell short of statistical significance (11.5% versus 6.9%, P = 0.078).
Forty-five of 96 cases (47%) had an AIDS cancer and 51 (53%) had a non-AIDS cancer (nonmelanoma skin cancer in 12, lung cancer in 9, anal cancer in 7, and prostate cancer or Hodgkin disease in 5 each). For these non-AIDS cancers, median CD4 count at cancer diagnosis ranged from 226 for Hodgkin disease to 670 for prostate cancer.
People with cancer were significantly more likely to be white (52.1% versus 37%, P = 0.004) and less likely to respond to HBV vaccination: The response rate was 37% in people with AIDS or non-AIDS cancer versus 60.7% in controls (P = 0.015). Although the vaccine response rate differed significantly between people with AIDS cancers and controls (P = 0.041), the difference fell short of statistical significance in a comparison between people with non-AIDS cancers and controls (P = 0.105).
To gauge the impact HBV vaccine response on cancer risk, Dando and colleagues engineered a multivariate model that considered age, various CD4 counts, exposure to combination antiretroviral therapy, race, opportunistic infection, CDC category B conditions, history of pneumonia, and white race. This model determined that failure to respond to the HBV vaccine and older age independently predicted an increased cancer risk in all of the following CD4-based calculations:
Risk of cancer when adjusted for CD4 count at initial visit (and other variables)
· Failure to respond to HBV vaccine: odds ratio [OR] 2.86, 95% confidence interval [CI] 1.22 to 6.77, P = 0.016
· Age at first visit (per additional year): OR 1.09, 95% CI 1.04 to 1.14, P < 0.001
Risk of cancer when adjusted for nadir CD4 count (and other variables)
· Failure to respond to HBV vaccine: OR 3.03, 95% CI 1.22 to 7.14, P = 0.017
· Age at first visit (per additional year): OR 1.08, 95% CI 1.03 to 1.13, P < 0.001
Risk of cancer when adjusted for whether nadir CD4 count was below 200 (and other variables)
· Failure to respond to HBV vaccine: OR 3.57, 95% CI 1.41 to 9.09, P = 0.008
· Age at first visit (per additional year): OR 1.09, 95% CI 1.04 to 1.14, P < 0.001
Risk of cancer when adjusted for CD4 count at first HBV vaccine dose (and other variables)
· Failure to respond to HBV vaccine: OR 2.94, 95% CI 1.14 to 7.69, P = 0.026
· Age at first visit (per additional year): OR 1.09, 95% CI 1.04 to 1.14, P < 0.001
Time to cancer diagnosis was significantly shorter in people who did not respond to HBV vaccination--19.4 versus 22 years (P = 0.006)--even after statistical adjustment for age, time-updated CD4 count, nadir CD4 count, and history of opportunistic infection (P = 0.03).
The Case Western team proposed that "common immune defects underlying vaccine response failure and development of cancer may be magnified in HIV infection and are incompletely understood."
Another study reported at the Conference on Retroviruses found that a positive response to HBV vaccination approximately halved the risk of HIV disease progression or death in the US Military HIV Natural History Study, regardless of antiretroviral exposure or CD4 count [5].
References
1. Dando S, Crowell T, Lederman M, Rodriguez B. Functional immune response is associated with risk of cancer in a cohort of HIV-infected patients. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 759. http://www.retroconference.org/2010/PDFs/759.pdf.
2. 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;52:203-208.
3. Burgi A, Brodine S, Wegner S, et al. Incidence and risk factors for the occurrence of non-AIDS-defining cancers among human immunodeficiency virus-infected individuals. Cancer. 2005;104:1505-1511.
4. Silverberg MJ, Neuhaus J, Bower M, et al. Risk of cancers during interrupted antiretroviral therapy in the SMART study. AIDS. 2007;21:1957-1963.
5. Landrum M, Huppler Hullsiek K, Crum-Cianflone N, et al. Hepatitis B vaccine response predicts progression to clinical AIDS or death. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 625. http://www.retroconference.org/2010/PDFs/625.pdf.
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