Age-Related Clonal Haematopoiesis in an HIV Evaluation Cohort (ARCHIVE)
It is well-known that the ageing process in people with HIV (PHIV) differs from that in people without HIV. PHIV have accelerated biological ageing processes and more age-related medical comorbidities and are more frail than people without HIV. However, the reasons for this are not very well understood. As PHIV are now living longer with modern HIV treatment, HIV research and clinical care has become focused on understanding how HIV affects the ageing process and what can be done to optimise the health of ageing PHIV. This study focuses on comparing ageing-related molecular processes and clinical outcomes across HIV status.
The ARCHIVE study is a longitudinal cohort study that was established to evaluate ageing-related molecular and clinical processes in older adults with and without HIV.
The first study visit enrolled 426 individuals (220 with HIV and 226 without HIV) in 2018-2019 to compare the presence of clonal haematopoiesis (CH) in the blood of people with and without HIV. CH is a common finding in older people that develops when a genetic mutation (a small change to your DNA) is present within a small number of blood cells. Up to one in 10 people over the age of 60 years will have CH.
CH is significant because it has been linked to increased inflammation and an increased risk of blood cancers and cardiovascular diseases. A second study visit was completed from 2021-2022 which evaluated links between CH and geriatric syndromes (frailty, multimorbidity and quality of life) across HIV status.
To date, four studies have been published on the ARCHIVE Study (links in sidebar). The main publications and findings include:
Dharan et al. Nature Medicine 2021
- CH was twice as common in participants with HIV than participants without HIV.
- Participants with HIV and CH also had higher levels of certain blood cell counts and markers of inflammation.
- We did not find that participants with HIV and CH had a higher rate of medical conditions such as heart problems or blood cancers, however larger studies are needed.
Han Cell Reports Medicine 2024
- CH was linked to frailty and reduced quality of life, in both participants with and without HIV
- Accelerated phenotypic age (another measure of biological age) was increased in participants with HIV
- Poor diet quality (increased red and processed meat consumption) and increased microbial gut translocation (“leaky gut”) were associated with CH in both participants with and without HIV
CH was associated with increased liver fibrosis
Behrouzfar et al. Comms Biology 2026 (in press)
HIV was associated with a lower prevalence of mosaic chromosomal alterations (mCA), particularly loss of chromosome Y, in PWH compared to participants without HIV. mCA are another type of genetic alteration that can lead to clonal haematopoiesis.
ARCHIVE is the only study globally that has been designed to prospectively evaluate CH in people with and without HIV over time; therefore, this body of work has contributed greatly to the emerging global data on CH in people living with HIV. Ongoing work in ARCHIVE is planned in the coming one to two years to further evaluate CH over time and further explore the gut health associations we have found (diet and gut translocation), and link them to clinical outcomes.
The overall goal of this work will be to identify ways to screen individuals at risk of CH and explore potential interventions that may slow biological ageing and the adverse health conditions associated with the condition. Our goal is to understand why CH is more common in people with HIV, trial preventive measures to reduce CH, and improve health outcomes in this growing population.
- Monash University
- Peter MacCallum Cancer Centre
- St Vincent’s Centre for Applied Medical Research
- Holdsworth House Medical Centre
- Prahran Market Clinic
- East Sydney Doctors
- RPA Sexual Health
- The Alfred
- Taylor Square Medical Practice
- Monash Health
- Albion Street Clinic
National Health and Medical Research Council (NHMRC); Department of Health and Ageing; Gilead Sciences; UNSW; Royal Australasian College of Physicians; 2025 MRFF Early-to-Mid Career Researchers Scheme.
