Human Immunodeficiency Virus and Clonal Hematopoiesis

Abstract

The evolution of antiretroviral therapies (ART) has tremendously improved the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH), which is currently similar to the general population. However, as PLWH are now living longer, they exhibit various comorbidities such as a higher risk of cardiovascular disease (CVD) and non-acquired immunodeficiency syndrome (AIDS)-defined malignancies. Clonal hematopoiesis (CH) is the acquisition of somatic mutations by the hematopoietic stem cells, rendering them survival and growth benefit, thus leading to their clonal dominance in the bone marrow. Recent epidemiologic studies have highlighted that PLWH have a higher prevalence of CH, which in turn is associated with increased CVD risk. Thus, a link between HIV infection and a higher risk for CVD might be explained through the induction of inflammatory signaling in the monocytes carrying CH mutations. Among the PLWH, CH is associated with an overall poorer control of HIV infection; an association that requires further mechanistic evaluation. Finally, CH is linked to an increased risk of progression to myeloid neoplasms including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which are associated with particularly poor outcomes among patients with HIV infection. These bidirectional associations require further molecular-level understanding, highlighting the need for more preclinical and prospective clinical studies. This review summarizes the current literature on the association between CH and HIV infection.

Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV: a report from the REPRIEVE trial

“… 12 The excess ASCVD risk associated with TET2 CHIP is believed to be at least partly mediated through heightened inflammation via the NLRP3/IL-1β/IL-6 pathway. 13 , 14 More recently, smaller studies have revealed a higher prevalence of CHIP among PWH, particularly in older age groups, 15 , 16 , 17 , 18 which has been proposed as a predictive marker for future ASCVD events among PWH without traditional risk factors. 7 …”

Clonal hematopoiesis of indeterminate potential in persons with HIV

“…IL-1 receptor antagonist (IL-1Ra), because of its longer half-life, represents a practical peripheral marker for inflammasome activity. Moreover, IL-2, which is an inducer of clonal expansion of CD4 þ T cells and of monocyte activation, along with the antiinflammatory marker IL-10, have also been linked to CHIP [15][16][17]. TET2-associated activation of the NLRP3 inflammasome provides a pathophysiological framework, which exemplifies how CHIP might influence inflammation.…”