Increased CHIP Prevalence Amongst People Living with HIV

Area of Science:

• Hematology
• Immunology
• Cardiovascular Disease

Background:

• People living with human immunodeficiency virus (PLWH) face elevated cardiovascular disease (CVD) risk, partly due to chronic inflammation and immune dysregulation.
• Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the expansion of mutated hematopoietic stem cells, is linked to hematologic malignancies and coronary artery disease (CAD).
• Inflammation is implicated in both CHIP development and its association with CVD, prompting investigation into CHIP prevalence in PLWH.

Approach:

• A comparative analysis was conducted using exome sequence data from blood DNA.
• CHIP prevalence was assessed in 600 individuals from the Swiss HIV Cohort Study (SHCS) and 8,111 controls from the Atherosclerosis Risk in the Communities (ARIC) study.
• Propensity score matching was employed to create a subset of 230 SHCS cases and 1002 ARIC controls for robust comparison, controlling for demographic disparities.

Key Points:

• The study found a significantly higher prevalence of CHIP in PLWH (7%) compared to controls (3%), as identified in both the overall cohort and the propensity-matched subset (p=0.005).
• The ASXL1 gene mutation was the most frequent driver of CHIP in the SHCS cohort, differing from the ARIC cohort.
• These findings indicate a strong association between HIV infection and an increased prevalence of CHIP.

Conclusions:

• HIV infection is associated with an increased prevalence of CHIP.
• CHIP may represent a mechanistic link contributing to the heightened cardiovascular risk in PLWH.
• Further prospective research is warranted to confirm CHIP's role in the excess CVD risk among PLWH.