HIV-induced immune deficiency is associated with a higher risk of hepatocarcinoma, ANRS CO3 Aquitaine Cohort, France, 1998-2008.

BACKGROUND & AIMS: HIV and viral hepatitis co-infected patients are at high risk for hepatocarcinoma. The contribution of immunodeficiency is not well documented. We aimed at estimating the relationship between the occurrence of hepatocarcinoma and both types of measures of immunodeficiency, current and cumulative (time below a given threshold), to assess their independent effects. METHODS: HIV-infected adults included in the ANRS CO3 Aquitaine Cohort with no history of cancer, ≥ 3 months of follow-up between 1998 and 2008, ≥ 1 CD4+ cell count (CD4+), and documented hepatitis virus status were eligible. Extended Cox proportional hazards models with delayed entry were used to estimate the risk of hepatocarcinoma. Exposure to a CD4+ < 350 or <500 cells/mm(3) (current and cumulative duration) was time-updated. Hepatitis B or C virus co-infection and gender were fixed-effect variables. RESULTS: Sixteen cases of hepatocarcinoma were diagnosed among the 2864 eligible patients, the incidence rate was 0.78 case/1000 person-years (95% Confidence Interval [CI]: 0.40-1.16). Current CD4+ < 350 or < 500 was independently associated with a higher risk of hepatocarcinoma (Hazard Ratio [HR]: 5.0, CI 1.5-16.8, p = 0.009 and HR = 10.3, CI 1.3-82.8, p = 0.029, respectively). The occurrence of hepatocarcinoma was independent of the cumulative exposure to a CD4+ < 350 or < 500 (p = 0.38 or p = 0.80, respectively). CONCLUSIONS: Presenting with CD4+ < 500 was associated with a higher risk of hepatocarcinoma, whereas the cumulative duration with immunodeficiency was not. These results suggest that moving CD4+ count above 500 following antiretroviral therapy initiation is associated with a decreased risk of hepatocarcinoma, regardless of the duration of HIV-induced immunodeficiency.

CMV plasma DNAemia and risk of cancer among HIV-infected patients: a case-control study nested in the ANRS CO3 Aquitaine Cohort, France, 2002-2007.

BACKGROUND: CMV reactivation, which enhances immune senescence, could be associated with a higher risk of cancer. OBJECTIVES: We compared the prevalence of positive CMV DNAemia in HIV-infected patients with and without cancer. STUDY DESIGN: This case-control study, nested in the ANRS-CO3 Aquitaine Cohort, included patients with a first diagnosis of cancer (2002-2007) as cases. Two controls were matched per case. Cancer risk was estimated using conditional logistic regression models, an Odds Ratio (OR) of 2 could be detected with 80% power. The variables considered were: ≥ 1 positive CMV DNAemia, CD4+ and CD8+ counts, HIV plasma load. Plasma CMV DNA was retrospectively quantified within the 3-year period preceding the endpoint. RESULTS: The 143 cases (93 non-AIDS-related and 50 AIDS-related cancers) and 284 controls had a median age of 47 years (IQR: 41-56). At the time of diagnosis or censorship, for cases and controls, median values were respectively, for CD4+ count: 327 cells/mm(3) (IQR: 164-514) and 416 (IQR: 275-582), and for HIV plasma load: 2.6 log(10)copies/mL (IQR: 1.7-4.7) and 1.7 log(10)copies/mL (IQR: 1.7-3.3). We performed 2056 CMV PCR; 14 cases (9.8% [95% CI: 4.9-14.7]) and 19 controls (6.7% [CI: 3.8-9.6]) presented ≥ 1 positive PCR. CMV DNAemia was not associated with the risk of cancer (unadjusted and adjusted p-values=0.19 and 0.54, respectively). HIV load >500 copies/mL was independently associated with a higher risk of cancer (OR=2.02; p=0.002; 95% CI: 1.29-3.17). CONCLUSION: This large case-control study did not show any differential exposure to positive CMV plasma DNAemia between cancer cases and controls.