Frailty among individuals with HIV was associated with a network of inflammatory proteins, changes in markers related to bone health and signs of T-cell exhaustion, according to a study published in The Journal of Infectious Diseases.
The study included 120 participants with HIV enrolled in the HIV Infection, Aging, and Immune Function Long-Term Observational Study (HAILO). Half met criteria for frailty, while the other half remained robust. Frailty was defined using a modified version of the Fried criteria, which considers unintentional weight loss, low physical activity, exhaustion, weakness and slow walking speed.
The authors measured inflammatory and other soluble markers in plasma and examined T-cell phenotypes to assess their relationships with frailty. According to the study, 19 of 75 plasma markers were significantly associated with frailty, with many related to nuclear factor kappa B, or NF-κB, signaling and the senescence-associated secretory phenotype (SASP).
“Our data are thus consistent with innate immune responses, inflammation, and signals of bone health being linked to frailty in [people with HIV],” the authors wrote.
The study also identified differences in T-cell populations. People with frailty had lower proportions of naïve CD4 and CD8 T cells and higher proportions of CD4 T cells expressing the immune checkpoint molecules TIGIT and PD-1, according to the study.
Osteoprotegerin (OPG), was among the markers linking bone health and immune changes with frailty. According to the authors, OPG was the soluble marker most strongly linked to T-cell phenotypes among participants with frailty. OPG and tumor necrosis factor levels were positively correlated with PD-1 expression and negatively correlated with the naïve CD4 T-cell phenotype.
The authors wrote that OPG "can inhibit osteoclast formation and prevent bone resorption."
They cautioned that the cross-sectional design does not establish whether the identified factors cause or predict frailty. They also noted that the cohort with frailty was relatively young and mostly had a Fried score of 3, limiting their ability to assess more advanced frailty, and that the relevance of the findings to the general population remains unclear.
"Our data are consistent with a pathogenic link between inflammation, T-cell activation, bone health, and frailty in [people with HIV]," they concluded.
Kristine M. Erlandson, MD, reported grant funding from Gilead and consulting payments from Gilead, ViiV, and Merck, all outside the submitted work. The other authors reported no financial conflicts of interest.
