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What CD4 cell count levels are associated with a reduced risk of cancer?
N. Crum-Cianflone1,2, K. Huppler Hullsiek1,3, V. Marconi1, A. Weintrob1, A. Ganesan1, R.V. Barthel1, B. Agan1, and the Infectious Disease Clinical Research Program
1Infectious Disease Clinical Research Program, Bethesda, United States, 2Naval Medical Center San Diego, San Diego, United States, 3University of Minnesota, Minneapolis, United States
Background: Cancers are an increasing cause of morbidity and mortality among HIV-infected persons. The relationship between longitudinal CD4 counts and the development of malignancies remains poorly defined, especially for non-AIDS-defining cancers (NADCs).
Methods: We examined data collected from a multicenter, prospective, observational study, which enrolled 4,969 HIV-positive persons (37,645 person-years) from 1984 to 2008. Multivariate Cox proportional hazard models (adjusted for age, race, gender, and year of HIV diagnosis) were used to evaluate time-updated CD4 strata with cancer development. Hazard ratios (HR) are given with 95% confidence intervals (CI).
Results: Cancer occurred among 513 (10.3%) HIV-infected persons: 319 were AIDS-defining cancers (ADCs) and 194 were NADCs. The median age of the cohort at HIV diagnosis was 28 years; 91% were male; 44% were African Americans and 43% Caucasians. The median CD4 counts proximal to ADC and NADC events were 70 and 443 cells/mm3, respectively. The risk of cancer was related to CD4 counts during follow-up and varied by cancer type. Compared to CD4 counts > 500 cells/mm3, the risk of an ADC was elevated at CD4 counts < 200 (HR 19.6; 95 CI% 12.7-30.4), 200-349 (HR 3.4; 95% CI 2.0-5.6) and 350-499 (HR 1.8; 95% CI 1.1-3.2). The risk of an NADC event was not significantly increased for CD4 counts < 500 (HR 1.2; 95% CI 0.9-1.6) compared to > 500. However, compared to those with CD4 count > 700 cells/mm3, NADCs were increased at CD4 counts < 500 (HR 1.7; 95% CI 1.1-2.7) and 500-699 (HR 1.8; 95% CI 1.1-3.0).
Conclusions: While the risk of ADCs was highest at CD4 counts < 200 cells/mm3, increased risk was also present at < 500. There was an association between NADCs and CD4 counts < 700 cells/mm3 during follow-up. Maintaining robust CD4 counts may be useful in reducing cancer events among HIV patients.
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