Measures of longitudinal immune dysfunction and risk of AIDS and non-AIDS defining malignancies in antiretroviral treated people with human immunodeficiency virus (HIV). Clinical Infectious Disease
Chammartin et al. for the RESPOND Study Group aimed to assess whether CD4:CD8 ratio and CD8 cell counts may be useful biomarkers for the risk of non-AIDS defining malignancies (NADM), AIDS-defining malignancies (ADM) and specific cancers, after accounting for known risk factors of cancers and sociodemographic participant characteristics.
The authors found found that CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI}1.10–6.19] and 2.03 [95% CI 1.24–3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies.
In conclusion, in this large cohort study with pooled data on people with HIV across Europe and Australia, a CD4 cell count of<350 cells/µL was associated with an increased risk of any studied malignancy. The study provides additional evidence that a low CD4:CD8 ratio carries an additional risk for ADM and infection-related malignancies. Therefore, regular monitoring of CD4 cells and CD4: CD8 ratios may provide benefit if it leads to enhanced cancer screening strategies for individuals who initiate ART late and do not achieve immune restoration above 350 cells/µL and >1.0, respectively. The study findings illustrate the importance of early HIV diagnosis and ART initiation with lifelong HIV suppression to reduce, in addition to other relevant clinical events, the risk of ADM and NADM. Whether people with HIV with insufficiently restored immune function profit on top of smoking cessation counselling from enhanced cancer screening programs should be further investigated.