Characteristics of solid versus hematologic malignancies in people living with human immunodeficiency virus.

Abstract

Purpose: People living with HIV (PLWH) face increased risks of both AIDS-defining and non-AIDS-defining malignancies. We characterized the age-standardized cancer burden, compared clinical characteristics and survival outcomes between hematologic and solid malignancies in PLWH, and performed a secondary analysis stratifying malignancies by viral oncogenesis.

Methods: We conducted a retrospective cohort study of 166 PLWH diagnosed with cancer at a 407-bed tertiary academic medical center in the southern United States between 2019 and 2025. Age-standardized cancer rates proportions were calculated using the direct standardization method with the US 2000 Standard Population as the reference. Demographic, HIV-related, and clinical variables were compared between hematologic and solid malignancies using univariate and multivariate logistic regression. Cox proportional hazards regression and restricted mean survival time analysis were performed to identify predictors of overall survival. The analysis was repeated for virus-driven versus non-virus-driven malignancies.

Results: Among 3,640 HIV-positive patients actively receiving care at our institution, 166 (4.6%) were identified as having both HIV infection and a concurrent malignancy. The age-standardized cancer detection proportion was 888.1 per 100,000 patients (95% CI 753.0-1023.2). Hematologic malignancies occurred at a younger age than solid tumors (median 41 vs. 51 years, p = 0.002) and were associated with higher HIV viral loads, lower CD4 + counts, and poorer antiretroviral therapy adherence. High HIV viral load remained independently associated with hematologic malignancy in multivariate analysis (OR 4.839, 95% CI 1.495-17.58). Kaplan-Meier analysis demonstrated a trend toward lower overall survival among hematologic malignancy patients compared with solid tumor patients (log-rank p = 0.056), which reached significance after age adjustment in multivariate Cox proportional hazards regression (HR 3.00, 95% CI 1.35-6.66, p = 0.007). In the virus-driven analysis, both high HIV viral load and low CD4 + T-cell count were independently associated with virus-driven malignancy, with CD4 + T-cell count demonstrating a particularly strong association (OR 5.129, 95% CI 1.709-17.153, p = 0.005).

Conclusion: Immune dysfunction remains strongly associated with hematologic malignancies in PLWH, whereas solid tumors are increasingly associated with age- and lifestyle-related factors. A secondary analysis stratifying malignancies by viral oncogenesis identified consistent associations between immune dysfunction and virus-driven malignancy, further supporting the role of impaired immune surveillance in HIV-associated cancer development.

Clinical trial number: Not applicable.