Clonal Hematopoiesis in HIV and Aging

The potential role of clonal hematopoiesis (CH) --the proliferation of hematopoetic stem cells with acquired mutations that confer a competitive growth advantage-- in promoting inflammation and aging-related complications in people living with HIV (PLWH) is unknown. While the prevalence of CH in the general population increases with age and is a potential pre-malignant, pro-inflammatory state associated with cardiovascular disease and mortality, there is a major gap in our knowledge about the prevalence and impact of CH in PLWH compared to controls without HIV. In a mouse model, bacterial translocation across the gut barrier via compromised epithelial tight junctions of the gastrointestinal tract causes endotoxin-responsive expansion of CH clones via toll-like receptor dependent pathways. An analogous state of compromised intestinal integrity in chronic HIV infection may favor expansion/persistence of CH clones. Our overarching hypothesis is that CH is more prevalent in PLWH and contributes to accentuated/accelerated aging.  We are investigating this in the MACS WIHS Combined Cohort Study supported by an R21 grant from the National Institute on Aging.  This collaboration includes basic scientists (Monica Guzman, PhD; Duane Hassane, PhD), statisticians (Donald Hoover, PhD [Rutgers University]; Qiuhu Shi, PhD [New York Medical College]), HIV/aging researchers (Marshall Glesby, MD, PhD; Eugenia Siegler, MD; Anjali Sharma, MD [Albert Einstein College of Medicine]), and a cognitive psychologist (Leah Rubin, PhD [Johns Hopkins University).