Frailty syndrome is commonly seen in the aged and reflects multi-system physiological change. However, with reduced functional reserve and resilience frailty is also known to be common in the HIV infected population. This study outlined an easily administered screening test to identify HIV patients with frailty. When significant components of frailty are identified, clinicians will be able to focus on amelioration of the problem and promote reversion to the pre-frail state.
En enkel, valideret protokol består af et batteri af tests er tilgængelige til at identificere ældre patienter med skrøbelighed syndrom. Dette syndrom af nedsat reserve og modstandsdygtighed over for stressfaktorer stiger i forekomsten med stigende alder. Hos ældre kan skrøbelighed forfølge en trinvis tab af funktion fra ikke-skrøbelig til at pre-skrøbelig til svagelige. Vi studerede skrøbelighed i HIV-inficerede patienter og fandt, at ~ 20% er skrøbelige hjælp Fried fænotype med strenge kriterier udviklet til ældre 1,2. I HIV-infektion syndrom forekommer i en yngre alder.
HIV-patienter blev kontrolleret for 1) utilsigtet vægttab, 2) langsomhed som bestemt ved ganghastighed, 3) svaghed som målt ved et greb dynamometer, 4) udmattelse ved svar på en depression skala, og 5) lav fysisk aktivitet blev bestemt ved at vurdere forbrændte kilokalorier i en uges tid. Pre-skrøbelighed var til stede med to af fem kriterier, og skrøbelighed var til stede, hvis tre afde fem kriterier var unormal.
Testene tager ca 10-15 min at udfylde, og de kan udføres af medicinske assistenter under rutinemæssige klinik besøg. Testresultater er scoret ved at henvise til standard tabeller. Forståelse hvilken af de fem bestanddele bidrager til skrøbelighed hos en individuel patient kan tillade klinikeren at belyse relevante underliggende problemer, hvoraf mange ikke er tydeligt i rutinemæssige HIV klinik besøg.
Centers for Disease Control projekter, mere end halvdelen af HIV-1-inficerede individer i USA vil være over 50 år i 2015. Den stigende levealder af HIV-1-inficerede patienter har resulteret i en uventet stigning i aldersrelaterede komorbiditeter, placerer HIV-positive ældste har øget risiko for sygelighed og dødelighed. Et vigtigt eksempel herpå er den nyligt beskrevne syndrom skrøbelighed, som kan spille en vigtig rolle i accelereret ældning af HIV-1-inficerede voksne. 3-7
Frailty er blevet defineret i alderen som en biologisk syndrom af nedsat reserve og modstandsdygtighed over for stressfaktorer, som følge af den kumulative nedgang i fysiologiske systemer og ofte skrider i en trinvis funktionelle tilbagegang over tid. Den kliniske betydning af skrøbelighed er, at syndromet betragtes som en højrisiko-tilstand, prædiktiv for negative sundhedsresultater såsom nedsat funktion og mobilitet, hospitalization og død. 8. Talrige undersøgelser i de sidste 10 år har forsøgt at vurdere skrøbelighed i forskellige befolkningsgrupper. Fried et al. Studerede skrøbelighed hos mænd og kvinder over 65 år, som var indskrevet i en hjerte-kar-studie. 2. Deres definition af skrøbelighed blev valideret i en undersøgelse af aldrende kvinder. 9 Ændringer af deres definition er blevet anvendt i andre undersøgelser, herunder HIV-1-inficerede personer. 4-7 Fried et al. beskrev en skrøbelig fænotype, at selv i mangel af handicap eller co-morbiditet viste, at 7% af befolkningen over 65 år er skrøbelig henviser til, at 20-26% ældre end 80 år var skrøbelig. 2 Frailty kan være en primær resultat, men også en sekundær diagnose som følge af en akut begivenhed eller co-morbiditet som malignitet, åreforkalkning, infektion (HIV) eller depression. 10. Derudover andre faktorer, der vil bidrage til skrøbelighed hos hiv-patienter, for eksempel, intravenøst stofmisbrug,armod og psykisk sygdom.
Frailty er fundet i HIV-1-inficerede patienter på yngre aldersgrupper end ikke-HIV-inficerede patienter. 4. Ældre HIV-1-inficerede individer ofte til stede med mere alvorlig hiv-sygdom og har en kortere overlevelsestid end yngre individer, ofte fordi de ikke er diagnosticeret indtil meget sent i sygdomsforløbet. 11. En anden årsag kan være, at ældre patienter har flere co-morbide sygdomme interagerer med HIV-1. Ældre HIV-1-inficerede individer er blevet beskrevet som skrøbelige end alder-matchede kontrol individer uden HIV-1 infektion. 4.
Klinisk måling af skrøbelighed i HIV-1-inficerede patienter er vigtig, da skrøbelighed kan være reversible i sin vorden (f.eks indgreb for at vende dekonditionering, protein-energi underernæring, depression, D-vitaminmangel og andre skrøbelighed tilknyttede betingelser), før forarmet reserver nå en kritisk tærskel, der fører tilirreversibel sårbarhed og funktionelle tilbagegang.
Previous studies of HIV and frailty: Two retrospective studies by Desquilbet et al. assessed frailty in a cohort of men who have sex with men from the Multicenter AIDS Cohort Studies (MACS). Both studies used a shortened definition of frailty containing fewer criteria than did our study. The first study compared frailty in HIV-1 infected men in the pre-treatment era to a control group of HIV uninfected men.4 There were similar rates of frailty in HIV+ men older than 55 years and HIV- men older than 65 years; frailty was found to occur earlier in HIV-1 infected men. Our study had similar findings of an earlier occurrence of frailty phenotype, but we obtained higher rates of frailty compared with MACS, possibly because our use of the full Fried frailty criteria versus surrogate administrative data, but also because of the different population of patients in our study.
Another study by Desquilbet et al. evaluated CD4 cell count and HIV viral load as predictors of frailty in HIV+ men and found that lower CD4 cell counts and viral loads of more than 50,000 copies of RNA were significantly associated with frailty.5 Also the prevalence of frailty declined in the era of ART. Despite differences in measuring frailty and in population characteristics our study concluded like Desquilbet et al. that a low CD4 cell count is significantly associated with frailty and that patients on long-term ART have less likelihood of developing frailty.1 Premature occurrence of prevalence of frailty, shorter duration of ART, more co-morbidities and lower CD4 count were associated with frailty in both studies, but we did not find a strong association between psychiatric diagnosis and frailty. We found a positive relationship between length of ART and not being frail (Figure 1).
Our findings of frailty in HIV patients: Our initial hypothesis that age was not significantly important when measuring frailty of patients with low CD4 cell counts was confirmed. Frailty is likely more causally related to the inflammatory state and profound immunosuppression found in many patients with low CD4 cell counts. Many of these patients had a history of recently treated opportunistic infections. Because of these observations we propose that an active diagnosis of AIDS (CD4 cell count <200 cells/μl) is a significant co-morbidity itself and significantly predisposes patients to being frail. All of our frail patients had at least one co-morbidity besides HIV itself. Our frail patients <50 years had significantly fewer co-morbidities than the frail population >50 years, though in comparison, the younger people had a lower CD4 cell count.
Our other hypothesis was that frailty may be temporary in younger patients with low CD4 cell counts and may revert when CD4 cell counts improve. We were limited by the low number of patients and this hypothesis could not be proven, but it was a likelyexplanation for the small number of patients in which reversal was demonstrated (Table 1). Longer antiretroviral treatment was found to be protective for frailty (Figure 1). This fact on its own would support the recommendations of starting ART at higher CD4 counts and continuing ART without any treatment breaks. We believe that the main reason by which length of ART treatment was shown to be protective for frailty is that patients on long term treatment are more likely to have better control of co-morbidities as well as HIV and less likely to be frail.
In conclusion we have observed an association between low CD4-cell counts and frailty, which is not affected by age, viral load or the presence of co-morbidities. Effective treatment with ART plays a protective role against frailty, reinforcing the importance of effective ART. Early implementation of ART in the care of HIV patients may protect against frailty. Though not tested in our study, future research should address other interventions known to reverse frailty in the aged including treating deconditioning, protein-energy malnutrition, depression, and vitamin D deficiency.
The authors have nothing to disclose.