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2013 ; 27
(9
): 1433-41
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Predicting risk of cancer during HIV infection: the role of inflammatory and
coagulation biomarkers
#MMPMID23945504
Borges ÁH
; Silverberg MJ
; Wentworth D
; Grulich AE
; Fätkenheuer G
; Mitsuyasu R
; Tambussi G
; Sabin CA
; Neaton JD
; Lundgren JD
AIDS
2013[Jun]; 27
(9
): 1433-41
PMID23945504
show ga
OBJECTIVE: To investigate the relationship between inflammatory [interleukin-6
(IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and
cancer risk during HIV infection. DESIGN: A prospective cohort. METHODS:
HIV-infected patients on continuous antiretroviral therapy (ART) in the control
arms of three randomized trials (N=5023) were included in an analysis of
predictors of cancer (any type, infection-related or infection-unrelated). Hazard
ratios for IL-6, CRP and D-dimer levels (log2-transformed) were calculated using
Cox models stratified by trial and adjusted for demographics and CD4+ cell counts
and adjusted also for all biomarkers simultaneously. To assess the possibility
that biomarker levels were elevated at entry due to undiagnosed cancer, analyses
were repeated excluding early cancer events (i.e. diagnosed during first 2 years
of follow-up). RESULTS: During approximately 24,000 person-years of follow-up
(PYFU), 172 patients developed cancer (70 infection-related; 102
infection-unrelated). The risk of developing cancer was associated with higher
levels (per doubling) of IL-6 (hazard ratio 1.38, P<0.001), CRP (hazard ratio
1.16, P=0.001) and D-dimer (hazard ratio 1.17, P=0.03). However, only IL-6
(hazard ratio 1.29, P=0.003) remained associated with cancer risk when all
biomarkers were considered simultaneously. Results for infection-related and
infection-unrelated cancers were similar to results for any cancer. Hazard ratios
excluding 69 early cancer events were 1.31 (P=0.007), 1.14 (P=0.02) and 1.07
(P=0.49) for IL-6, CRP and D-dimer, respectively. CONCLUSION: Activated
inflammation and coagulation pathways are associated with increased cancer risk
during HIV infection. This association was stronger for IL-6 and persisted after
excluding early cancer. Trials of interventions may be warranted to assess
whether cancer risk can be reduced by lowering IL-6 levels in HIV-positive
individuals.