Frailty, Housing Instability Drive Mortality Risk in People With HIV

Housing instability in people with HIV contributes to frailty, which significantly increases their risk of mortality, according to abstracts presented at the Conference on Retroviruses and Opportunistic Infections 2025.

In the general population, frailty is an aging-related risk factor for poor outcomes; individuals experiencing frailty face up to a 2.5 times higher risk of mortality. This concern is amplified for people with HIV, who experience chronic immune activation, high rates of comorbidities, and polypharmacy.

Consequently, frailty develops up to a decade earlier in those with HIV. Housing instability is also independently linked with the early onset of aging-related comorbidities, including frailty. Therefore, the researchers stressed the importance of better understanding the impact of frailty in this population and the connection between housing status and frailty.

These posters highlight the compounded challenges faced by people with HIV. | Image Credit: fizkes - stock.adobe.com

Frailty, Mortality Risk in People With HIV

The first poster assessed frailty status and all-cause mortality among people with HIV in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between 2015 and March 20241; the CNICS data repository compiles information on self-reported outcomes and clinical, demographic, and behavioral factors among those with HIV.

The researchers defined frailty using a validated phenotype of 4 components: weight loss, activity, mobility, and fatigue. Also, they ascertained all-cause mortality with multiple approaches, including national death indexes and state death certificate data.

With this information, the researchers used Cox proportional hazards models to estimate the association between time-updated frailty status (robust, prefrail, frail) and all-cause mortality. They restricted the models to people with HIV with complete case data and adjusted them for various factors, such as age, HIV viral load, and body mass index.

The study population consisted of 6737 eligible people with HIV. At baseline, the mean (SD) age was 50 (12) years, and most were male (85%). In terms of frailty status, 44% were prefrail and 11% were frail.

Over an average of 5.5 years of follow-up (median, 5.8 years), 360 deaths were recorded, yielding an incidence rate of 9.7 per 1000 person-years (95% CI, 8.8-10.8). In adjusted models, the researchers determined that frailty and prefrailty were associated with 2.48 (95% CI, 1.85-3.33) and 1.42 (95% CI, 1.10-1.83) times greater risks of death, respectively.

Similarly, they noted that prefrailty and frailty were consistently associated with an increased risk of death in models stratified by age (younger than 50 vs 50 or older) and sex (male vs female).

“Understanding and preventing frailty in this high-risk population remains a priority,” the authors concluded.

Housing Instability, Frailty in People With HIV

Building upon these findings, the second poster examined the relationship between housing status and frailty among people with HIV.2 Although living with HIV and experiencing housing instability are both independently associated with the early onset of aging-related comorbidities, including frailty, the researchers noted that in the past, few studies have examined the relationship between housing status and frailty among people with HIV.

To do so, they analyzed data from those with HIV engaged in care at 6 sites across the US within the CNICS between 2019 and 2024. Like the previous poster, the researchers considered people to be frail if they had at least 3 out of 4 of these components: fatigue, weight loss, inactivity, and/or immobility.

Additionally, housing status (homeless or unstable vs stable) was based on a person’s self-reported living situation in the last month. The researchers estimated the association between most recent housing status and frailty with prevalence ratios (PR) from generalized linear models using complete-case data.

They noted that their primary models adjusted for factors such as demographic characteristics, site, year, HIV clinical indicators, and substance use. However, sensitivity analyses excluded potential mediators, namely substance use and HIV clinical indicators, from the adjustment set.

The study included 6587 people with HIV, with most being male (84%) and virally suppressed (87%). Of these people, 8% (n = 505) had unstable housing (3% homeless; 5% unstable) and 11% (n = 700) were frail.

In the primary analysis, housing instability was associated with a 2.2 times higher prevalence of frailty (95% CI, 1.8-2.6). The researchers determined that this association was similar in models not adjusted for substance use (PR, 2.4; 95% CI, 1.9-2.8) or HIV clinical indicators (PR, 2.5; 95% CI, 2.1-3.0).

In stratified analyses, the researchers found a stronger association among virally suppressed people with HIV (PR, 2.5; 95% CI, 2.1-3.1) than those who were unsuppressed (PR, 2.5; 95% CI, 2.1-3.1; P = .04). They noted that this is likely due to the lower prevalence of frailty among stably housed, virally suppressed people with HIV (9%) compared with their unsuppressed counterparts (13%). However, frailty remained high (22%) among unstably housed people with HIV across both viral load groups.

Therefore, the researchers concluded that frailty and housing instability were both prevalent and strongly associated in people with HIV.

“These findings highlight the importance of social determinants of health, such as housing status, for clinical outcomes among all people with HIV,” the authors concluded.

References

1. Ruderman SA, Fahey CA, Kyle RP, et al. Frailty and all-cause mortality among people with HIV engaged in clinical care in the United States. Abstract presented at: Conference on Retroviruses and Opportunistic Infections; San Francisco, CA; March 9-12, 2025. Abstract 424.
2. Fahey CA, Ruderman SA, Whitney BM, et al. Housing instability and frailty among people with HIV engaged in clinical care in the United States. Abstract presented at: Conference on Retroviruses and Opportunistic Infections; San Francisco, CA; March 9-12, 2025. Abstract 424.