HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults

Abstract

People with HIV have higher rates of certain comorbidities, particularly cardiovascular disease and some malignancies, than people without HIV. As somatic mutations associated with agerelated clonal haematopoiesis (CH) are linked to similar comorbidities in the general population, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study recruiting 220 HIV-positive and 226 HIVnegative participants aged 55 years or older in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess for the presence of CH mutations and identify potential risk factors for and clinical sequelae of CH. Investigators testing for CH were blinded to participants' HIV status. In total, 132 CH mutations were identified in 99 (22.2%) of 446 participants. CH was more prevalent in HIV-positive participants than HIV-negative participants (27.7% vs. 16.8%, p =0.006), overall and across all age groups. HIV infection was associated with an increased odds of having CH (adjusted odds ratio 2.10, 95% confidence interval 1.30-3.38, p=0.002). The most common genes mutated were DNMT3A (48.5%), TET2 (20.5%) and ASXL1 (11.4%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.

The vicious and virtuous circles of clonal hematopoiesis

“…Thus, repeated or sustained exposure to inflammatory stimuli might leave them at a competitive advantage. The studies presented in this issue 2,3 describe the role of CH as both a driver of inflammation (primary CH) and its consequence (secondary CH). This could be conceptualized chronologically as follows: low-grade inflammation initially promotes clonal expansion of certain mutant HSPCs that, as the clone size increases, further promotes inflammation in a vicious circle that ultimately compromises organ function.…”

Clonal Hematopoiesis and Liquid Biopsy in Gastrointestinal Cancers

“…CH has been related to a number of negative health outcomes, with inflammation emerging as a significant mediator (40). Dharan et al (41) suggested that chronic HIV infection, might be an etiology for CH, whereas Bolton et al (42) established the relationship of CH with a wide spectrum of infections, including infection with SARS-CoV. Inflammation and clonal growth are reinforcing one other in a self-perpetuating circle.…”

Clinical Significance of Clonal Hematopoiesis of Indeterminate Potential in Hematology and Cardiovascular Disease

“…These data cannot be interpolated to CHIP in general, as mosaic chromosomal alterations represent a distinct subset of clonal hematopoiesis only partly overlapping with CHIP as defined here [ 11 , 89 ]. High rates of CHIP carriers have been described in patients with HIV [ 90 ], and a study suggested that CHIP could impair the effect of antiretroviral therapy [ 91 ]. The results of CHIP and SARS-CoV-2 infections are controversial but indicate an association of CHIP with severe COVID-19 in larger cohorts [ 92 , 93 , 94 ].…”