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

Nat Med. 2021 Jun;27(6):1006-1011. doi: 10.1038/s41591-021-01357-y. Epub 2021 Jun 7.

Abstract

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1-5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6-10, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / genetics
  • Aging / pathology
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / virology
  • Clonal Hematopoiesis / genetics
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methyltransferase 3A
  • DNA-Binding Proteins / genetics*
  • Dioxygenases
  • Female
  • HIV / pathogenicity
  • HIV Infections / complications
  • HIV Infections / epidemiology
  • HIV Infections / genetics*
  • HIV Infections / virology
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Inflammation / virology
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasms / complications
  • Neoplasms / epidemiology
  • Neoplasms / genetics
  • Neoplasms / virology
  • Proto-Oncogene Proteins / genetics*
  • Repressor Proteins / genetics*

Substances

  • ASXL1 protein, human
  • DNA-Binding Proteins
  • DNMT3A protein, human
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Dioxygenases
  • TET2 protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A

Associated data

  • ClinicalTrials.gov/NCT04641013