Retinol-Binding Protein 4 (RBP4), a Potential Biomarker of Frailty in HIV-Infected People on Stable Antiretroviral Therapy

J-R Blanco; L Romero; E Ramalle-Gómara; L Metola; V Ibarra; M Sanz; J-A Oteo; A Garcia; L Pérez-Martínez


HIV Medicine. 2020;21(6):358-364. 

In This Article

Abstract and Introduction


Objectives: A quantitative biomarker for identification of pre-frail and frail persons is still lacking. This study aimed to identify biomarker predictors of frailty in HIV-infected patients.

Methods: A cross-sectional study of HIV-infected patients who had been on antiretroviral therapy (ART) for at least 1 year and who presented an undetectable viral load (< 50 HIV-1 RNA copies/mL) at baseline was carried out. For each frail patient, up to four pre-frail and robust patients were randomly selected. The frailty status assessment was based on the five-item criteria described by Fried et al. Sociodemographic, anthropometric, biochemical and HIV-related characteristics were evaluated. Multiple potential biomarkers of frailty and a biological age biomarker were analysed.

Results: A total of 73 HIV-infected patients on ART for at least 1 year were evaluated. The patients were categorized as robust (n = 33), pre-frail (n = 32) and frail (n = 8) using the Fried criteria. All patients were on ART, with 100% undetectable viral load (< 50 copies/mL) at baseline. No significant differences in demographic, clinical or analytical characteristics were observed among patients in the different categories based on Fried criteria, with the exception of the veterans aging cohort study index (VACS). Similarly, no differences were observed in HIV-related characteristics, although nucleoside reverse transcriptase inhibitor (NRTI) use was less common in frail persons. The distribution of biomarker values varied according to frailty status, with frail persons having higher levels of interleukin (IL)-8, IL-18, CXC chemokine ligand 10 (CXCL10) and retinol-binding protein 4 (RBP4). In multivariable analysis, the assocation of frailty with RBP4 showed a tendency to statistical significance (odds ratio 1.0; 95% confidence interval 0.99–1.00; P < 0.05).

Conclusions: Differential biomarker expression was present according to Fried status. Longitudinal studies will clarify the utility of these biomarkers as targets for diagnostic or therapeutic intervention.


In the era of effective antiretroviral therapy (ART), the number of ageing HIV-infected people is increasing. However, the ageing process, which is accelerated in HIV-infected people,[1] is accompanied by more "aging-related" complications than in seronegative persons[2] which may predispose HIV-infected patients on ART to a frail state.[3–5]

Frailty is a clinical syndrome characterized by an increased vulnerability to adverse health outcomes. In the absence of a gold standard, frailty has been defined by phenotype criteria that include domains of unintentional weight loss, poor endurance, weakness, slow gait and low physical activity.[6] Frailty is clinically important, being associated with multiple adverse health outcomes and even death.[7–9] However, the reason for such associations could be biological rather than a problem of chronological ageing.[10] Indeed, from the perspective of HIV infection, the contribution of residual inflammation in persons on ART presenting an undetectable HIV viral load (VL) to the development of frailty is not well understood.

It would be of interest to obtain biomarkers that could be used as screening tools to identify pre-frail and frail patients during routine clinic visits and follow the effects over time of personalized interventions to improve their frailty status. Thus, using data from our cohort,[11] our objective was to identify biomarker predictors of pre-frailty and frailty in HIV-infected patients on ART presenting an undetectable VL.