Age-Related Clonal Hematopoiesis in Older Adults With HIV

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Investigators tested their hypothesis that people with HIV have a higher prevalence for clonal hematopoiesis.

The emergence of clonal hematopoiesis may provide a selective advantage in the context of chronic infection and inflammation among patients with HIV, according to research published in Nature Medicine. Results also suggest that HIV infection and clonal hematopoiesis are independently linked to elevated blood parameters and biomarkers associated with inflammation.

A team of investigators for the ARCHIVE study ( Identifier: NCT04641013) examined the genomic factors linked with aging and comorbidities among men and women older than 55 years with and without HIV to compare the frequency of somatic mutations of clonal hematopoiesis, to assess sociodemographic and clinical characteristics of all participants with characteristics in HIV-positive patients, and to investigate clinical outcomes such as inflammatory biomarker profiles and medical comorbidities in people with and without somatic mutations classified by HIV status.

The investigators aimed to test their hypothesis that people with HIV have a higher prevalence for clonal hematopoiesis.

A total of 446 participants aged 55 years and older were included in the analysis: 220 participants were HIV positive and 226 participants were HIV negative. The median age of the cohort was 63 years. and 96.2% were men. Among HIV-positive participants, the median number of years from diagnosis to enrollment was 24.

The investigators performed a targeted amplicon sequencing of genomic DNA from whole blood to assess the prevalence of clonal hematopoiesis in patients with and without HIV. Following sequencing, they found a higher prevalence of clonal hematopoiesis among HIV-positive participants.

Of the 446 participants, there were 135 clonal hematopoiesis-associated mutations found in 100 participants, of whom 62 were HIV positive and 38 were HIV negative (P =.004); 83 and 52 mutations were in HIV-positive and HIV-negative participants, respectively (odds ratio, 2.16; P =.002). Although the increased prevalence of clonal hematopoiesis was observed across all HIV-positive age groups, the highest prevalence was noted among participants who were older than 75 years.

The 3 most commonly mutated genes were DNMT3A (46.4%), TET2 (20.0%), and ASXL1 (13.3%). 

“Further clinical studies in larger and more diverse populations, including younger individuals, women with HIV and those who have not had sufficient access to [antiretroviral therapy], are needed to evaluate HIV-specific risk factors for [clonal hematopoiesis],” the authors noted. “These insights may inform future interventions to guide surveillance for and management of [clonal hematopoiesis] in people with HIV,” the investigators concluded.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Dharan NJ, Yeh P, Bloch M, et al; for the ARCHIVE Study Group. HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults. Nat Med. 2021;27(6):1006-1011. doi:10.1038/s41591-021-01357-y