Cancer Burden and Inflammaging Among People Living with HIV: An Inflammatory Biomarker Analysis from an Italian Cohort

Background/Objectives: Despite effective antiretroviral therapy, cancer remains a relevant comorbidity in people living with HIV (PLWH), with an increasing burden of non-AIDS-defining cancers (NADCs). We assessed cancer prevalence and systemic inflammation using a composite score based on routine inflammatory biomarkers. Methods: We conducted a retrospective cross-sectional study of PLWH in Ferrara, Italy. Cancer history, immunovirological parameters, IL-6, CRP, D-dimer, and monocyte counts were collected. A composite inflammatory score (0–4) was derived from biomarker abnormalities and compared between AIDS-defining cancers (ADCs) and NADCs. Results: Among 566 participants, 64 had a history of cancer (11.3%; 95% CI, 8.7–13.9%), accounting for 79 diagnoses: 23 (29.1%) ADCs and 56 (70.9%) NADCs. Most diagnoses (82.3%) were associated with inflammatory scores of 0–1, whereas 17.7% had scores of 2–4, with similar distributions between ADCs and NADCs (17.4% vs. 17.9%; p = 0.962). D-dimer elevation was more frequent among NADCs than ADCs (42.9% vs. 21.7%). Higher inflammatory scores were significantly associated with lower current CD4+ T-cell counts (p = 0.043). Conclusions: Cancer was a substantial comorbidity among PLWH, with NADCs predominating despite favorable immunovirological status. The composite score integrated routinely available inflammatory, coagulation, and immune parameters, with higher scores associated with lower CD4+ counts. Although inflammatory profiles did not differ significantly between ADCs and NADCs, this finding highlights the complexity of immune dysregulation in PLWH and the limitations of individual circulating biomarkers. Further validation of composite inflammatory scores may provide a clinically accessible framework for characterizing residual immune dysfunction and its relationship with cancer development and outcomes.