CTN 314: CHANGE HIV

Study Approach

The study will take place over 5 years in Toronto, Montreal and Vancouver, and aims to enroll a cohort of 750 people (80% men, 20% women). Data collection will occur in three phases, 18 months apart, with three study visits per phase for a total of nine study visits.

During each phase, a series of questionnaires, physical measurements, and blood tests will be collected. Data collected via questionnaire will cover the five domains of health: social support, quality of life, cognitive function, physical function, and mental health. Questionnaire data from the three study phases will be used to calculate a Health Aging Score (HAS) for each participant. Study investigators will analyze how personal, environmental, and HIV-specific factors affect health over time.

Researchers will also analyze the relationship between HAS, microbiome function, and inflammation. Biological specimens from the cohort will be collected and stored for use in potential future studies. Storing of samples for future use will be integral to the advancement of this area of study as new tests are developed and new markers related to healthy aging are identified.

Results

A total of 551 people living with HIV aged 65 and over participated in CHANGE HIV. Because the HIV epidemic largely emerged among men who have sex with men in Canada, 90% of the cohort were men and 9% were women. Most participants had lived with HIV for 20–40 years. The researchers used the Healthy Aging Score (HAS) throughout the study to assess how well participants aged. The HAS measures domains of health including quality of life, social support, physical function, mental health, and cognitive function.

Initial results from CHANGE HIV showed that only 5% of men and 10% of women reported no comorbidities. Of those who did, high cholesterol and high blood pressure were the most common. Later research revealed that people with two or more comorbidities (multimorbidity) were more likely to report severe disability. Severe disability is defined as difficulties performing day-to-day activities like getting dressed and walking. In the study, increased physical activity often reduced the association between multimorbidity and disability. Multimorbidity was also found to be associated with decreased health-related quality of life. In addition to comorbidities, this research also found that social factors, like stigma and loneliness, were associated with a lower quality of life among older people living with HIV.

Researchers found that 85% of participants had aging-related complex health issues (geriatric syndromes), the most common being polypharmacy (53%) and chronic pain (35%). Polypharmacy (taking five or more non-antiretroviral [ARV] medications) is a major issue for people aging with HIV. In a sub-study focused on polypharmacy, the researchers found that 53.8% of participants met the definition of polypharmacy and 14.6% met the definition of severe polypharmacy (taking 10 or more non-ARV medications). Furthermore, 49.3% were taking at least one potentially inappropriate medication (PIM; e.g., proton pump inhibitors and testosterone), 55.7% had a high total sedative burden, and 16.5% had a high anticholinergic burden. This study observed an increased likelihood of frailty with anticholinergic burden, sedative burden, severe polypharmacy, and number of PIMs, plus an increased risk of falls with high sedative burden and use of PIMs. . Anticholinergics are a class of medications that are used to treat respiratory conditions, bladder control, nausea and diarrhea and cramps- however because they inhibit parts of the nervous system they can also increase the risk of falls

The CHANGE HIV team also aimed to find molecular biomarkers that could identify healthy aging and help guide treatment and prevention of age-related comorbidities for people living with HIV. Molecular biomarkers can be objectively measured and used as an indicator of certain processes. An initial study of 247 CHANGE HIV participants revealed that GDF-15 and IL-6 were promising candidates. As GDF-15 levels decreased, healthy aging increased, and elevated GDF-15 levels were associated with lower HAS, decreased cognitive function, and frailty. Similarly, as IL-6 levels decreased, healthy aging increased, and elevated IL-6 levels were associated with lower HAS, lower self-rated health, and frailty.

Conclusion

CHANGE HIV has been instrumental in unveiling medical, social, and biological mechanisms of aging among people living with HIV. The findings from each study and substudy provide great foundations for future research and policies that will help people aging with HIV enjoy the best health and wellbeing possible.

Moving on from CHANGE HIV, a new project will soon be launching: CTNS 056. Led by CTN+ Treatment and Management Co-Lead, Dr. Alice Zhabokritsky, this study will co-design a deprescribing program to manage polypharmacy and potentially inappropriate medications in older adults living with HIV.