A study published in October in the Journal of Acquired Immune Deficiency Syndrome (JAIDS) had an unexpected finding: that being single and lonely—and, in contrast to other studies, not nadir CD4 count or multi-morbidity—correlated with frailty in older people with HIV (PWH).
The cross-sectional analysis included 439 participants over age 65 (with a median age of 69) from the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study. Frailty criteria included unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, and low physical activity, and participants experiencing three or more criteria are considered frail. Researchers found that just over 16% of participants met at least three criteria, while 62% met one or two criteria (and were considered prefrail) and 21% met no frailty criteria and were considered robust. After researchers adjusted for nadir CD4 count, age, gender, time since HIV diagnosis, and comorbidities, being single had an adjusted risk ratio of 2.09, or more than double.
In an email to POSITIVELY AWARE, the study’s author, Alice Zhabokritsky, MD, MSc, a professor at the University of Toronto Department of Medicine, said that her team differentiated being single from experiencing loneliness. “We found that the majority of study participants were not in a relationship (65%) but they reported various degrees of loneliness,” Zhabokritsky wrote. “Our study shows that companionship, whether through intimate relationships or social networks, is incredibly important for the health of older adults living with HIV.”
Acknowledging that many studies show that people with HIV (PWH) are more likely to experience frailty earlier than people without HIV (PWOH), due in part, though maybe not entirely, to chronic inflammation, stressors of older treatments (such as protease inhibitors) and even newer antiretroviral therapy (ART), Zhabokritsky suggested that findings from the CHANGE HIV study may suggest a bidirectional feedback loop of HIV-frailty-isolation. That is, social isolation could contribute to frailty, and frailty further exacerbates social isolation. Other comorbidities could also be part of that negative loop.
“Although it is difficult to know whether social isolation is a cause or a consequence of frailty (potentially contributing to both), our findings show that social connections can be protective as people age with HIV,” Zhabokritsky wrote. “Similar to other studies, we observed a higher prevalence of frailty in our cohort than in comparable cohorts of older adults in the general population although we did not observe a correlation between the nadir CD4 count (the lowest point of the immune system before treatment is started) and frailty in our cohort.”
At least one advocate urged against concluding that loneliness is more significant to the onset of frailty in older PWH than CD4 nadir, or immune dysregulation, in general.
“This study was cross-sectional, not prospective or retrospective,” said Jules Levin, director of the National AIDS Treatment Advocacy Program (NATAP). “I am convinced immunosuppression and a predisposition to low CD4 nadir, which predicts immune senescence [aging], does increase risk for frailty and cognitive impairment, and often these go together with older PWH,” Levin said.
Findings presented at the 2023 International Workshop on HIV and Aging showed that cognitive frailty affects PWH more than a decade earlier than PWOH. Other research concluded that prevalence of a frailty-related phenotype (FRP) that approximates a clinical definition of frailty, correlates with a lower CD4 count, independent of ART use.
“For life, you have a dysregulated immune system [with HIV] which leads to immune senescence,” Levin said, “which leads to ongoing lifetime viral low-level replication, which leads to immune activation, which causes inflammation and all that is associated with a higher risk of comorbidities. There’s [a higher risk of] heart disease, there’s diabetes, there’s peripheral artery disease, eyesight and hearing disability that aging people experience… Social isolation is associated with [comorbidities], in addition to all the other factors that cause social isolation, like social determinants of health. It’s multifactorial, but immune dysregulation is the link.
Social isolation could contribute to frailty, and frailty further exacerbates social isolation.
“Once you get to advanced frailty, there’s no coming back,” Levin added. “The only hope is that maybe you can catch it in prefrailty, and slow it down, undertake an exercise program, intervene with a high-quality diet, and prevent comorbidities.”
And, head off frailty by identifying and addressing social isolation and loneliness, the CHANGE HIV study suggests.
Zhabokritsky doesn’t dispute that HIV itself is key to the onset of frailty. She and researchers wrote that persistent immune dysregulation seems to play an important role in the development of frailty in people living with HIV in addition to multimorbidity, lifestyle factors, and social determinants of health.
“I think our study highlights just how important loneliness and social isolation are for the well-being [of] older adults living with HIV and points towards potential opportunities to attenuate risk of frailty,” Zhabokritsky wrote in an email. “For researchers, this may open new avenues for interventions to prevent development of frailty. Health providers are encouraged to inquire about loneliness and social isolation when seeing older adults living with HIV and linking those in their care to local communities and organizations.”
Resources for whole-person approach to aging with HIV
Screening for frailty—ideally for pre-frailty—can help prevent the worst health outcomes for many older PWH, whether they’re socially isolated or not, said Sean Cahil, director of Health Policy Research at the Fenway Institute, an LGBTQ+ health organization in Boston. Cahill pointed out that screening for frailty is among the American Academy of HIV Medicine’s recommendations for treating older patients with HIV. However, screenings—including for cardiovascular disease, chronic obstructive pulmonary disease (COPD), smoking, kidney disease, hypertension, diabetes, and osteoporosis—are standard of care, there are no data as to whether clinicians are adhering to them, or whether doctors are conducting pre-frailty screenings for PWH in their 50s, or 40s.
“Now we understand that some frailty and pre-frailty happens sometimes decades earlier [for PWH], and we see earlier onset of certain health conditions with people living with HIV,” Cahill said. “So I would say even if you’re in your 40s, and you want to get screened for something, ask your provider.”
Whether insurance will cover screenings at an earlier age is another open question, Cahill added.
Levin said that PWH will likely have to advocate for early screenings if doctors don’t provide them. “Despite several guidelines recommending screening for all people over 50, there’s no screening for frailty, bone mineral density and cognitive function. And unless you do frailty screening, doctors and clinics can’t discuss interventions with patients. Very few doctors do eyesight and hearing disability, and there is a direct link for eyesight and hearing disability with social isolation.”
“Interventions aimed at reducing loneliness should be assessed in people living with HIV to determine whether this could prevent or reverse frailty and ultimately improve functional status and quality of life,” Zhabokritsky and colleagues wrote. “In the interim, loneliness and not being in a relationship should be recognized by clinicians as potential indicators of frailty risk.”