b r a z j i n f e c t d i s . 2 0 1 6;20(1):99–102
ww w . e l s e v i e r . c o m / l o c a t e / b j i d
The
Brazilian
Journal
of
INFECTIOUS
DISEASES
Brief
communication
Human
immunodeficiency
virus
infection
and
its
association
with
sarcopenia
Lauro
Ferreira
da
Silva
Pinto
Neto
a,∗,
Marina
Cerqueira
Sales
b,
Eduarda
Sobral
Scaramussa
b,
Clara
Junia
Calazans
da
Paz
b,
Renato
Lirio
Morelato
caInfectiousDiseasesUnit,EscoladeCiênciasdaSantaCasadeVitoria(EMESCAM),Vitória,ES,Brazil bSantaCasadeVitória,Vitória,ES,Brazil
cGeriatricUnit,EscoladeCiênciasdaSantaCasadeVitória(EMESCAM),Vitória,ES,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received1August2015 Accepted9October2015
Availableonline25November2015 Keywords:
Sarcopenia HIV Frailty
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PresarcopeniaandsarcopeniawereevaluatedinHIV-infectedindividualsandinhealthy elderlycontrolsaccordingtotheconsensusdefinitionsoftheEuropeanWorkingGroupon SarcopeniainOlderPeople.Bioelectricalimpedance,ahydraulichanddynamometer,and gaitspeedwereusedtoevaluatemusclemass,musclestrength,andphysicalperformance, respectively.Adjustedandunadjustedbinarylogisticregressionpredictedtheriskof sar-copenia.PredictorcontributionwasassessedbytheWaldtest.Significancewasestablished atp≤0.05.TheHIV-infectedgroupconsistedof33patientsontreatment(42.4%women; meanage59±7years;meanBMI25±6kg/m2;viralloadundetectablein30cases).The
HIV-uninfectedgroupconsistedof60individuals(71.7%women;meanage70±7years;mean BMI28±6kg/m2).Ofthecontrols,4(6.7%)individualshadpresarcopeniaand4(6.7%)
sar-copeniacomparedto4(12.1%)and8(24.2%),respectively,intheHIV-infectedgroup.The HIV-infectedpatientshada4.95higherrisk(95%CI:1.34–18.23)forsarcopeniacompared tothecontrols.Itshouldbepointedoutthatthecontrolgroupwasonaverage10years older.Thisriskincreasedfurther(RR=5.20;95%CI:1.40–19.20)afteradjustingforageand BMI.HIV-infectedpatientswereshowntobeatagreaterriskofsarcopenia,anindicatorof frailty,evenfollowingadjustmentforageandBMI.
©2015ElsevierEditoraLtda.Allrightsreserved.
Thetermsarcopenia(sarxmeaningfleshandpeniapoverty) was first proposed by Irwin Rosenberg in1989 todescribe thedeclineinmusclemassassociatedwithage.1,2Currently,
theEuropeanWorkingGrouponSarcopeniainOlderPeople (EWGSOP)hasbroadened thisconcept byincludingmuscle strengthandphysicalperformanceasadditionaldiagnostic
∗ Correspondingauthorat:RuadrJoaoSantosNeves143,VilaRubim,Vitoria,ES29025-023,Brazil.
E-mailaddress:[email protected](L.F.d.S.PintoNeto).
criteria,andproposingthestagespresarcopenia,sarcopenia, andseveresarcopenia.3
Human immunodeficiency virus/acquired immunodefi-ciencysyndrome(HIV/AIDS)iscurrentlyconsideredachronic disease duetotheadvancesmadeinantiretroviral therapy (ART) in recent years. As the prevalence of opportunistic
http://dx.doi.org/10.1016/j.bjid.2015.10.003
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braz j infect dis.2016;20(1):99–102infections decreased, there was an increase in the preva-lence of chronic pathologies such as cardiovascular, liver, andkidneydiseases,cognitivedisorders,andosteoporosis.4
Thisfacthasgeneratedspeculationsinrelationtoaprobable “acceleratedagingsyndrome”inHIV-infectedpatients.5
Sev-eralinvestigatorshavedemonstratedbonemasslossand a greaterfractureriskinHIV-infectedpatients.6Whenever
pre-matureage-relatedcomorbiditiesaredetectedinHIV-infected patients,itiscrucialtoevaluatethepresenceofsarcopenia, animportantconditionresponsibleforanincreasedriskof fallsandfracturesthatmayultimatelyleadtoimmobilityand dependency.7Indeed,sarcopeniamayincreasemorbidityand
mortality.8
Theobjectiveofthiscross-sectional,analyticalstudywas to compare the prevalence of sarcopenia, presarcopenia, andseveresarcopeniainHIV-infectedpatientscomparedto healthyHIV-uninfectedelderlyindividuals.
Thestudywasconductedatthesexuallytransmitted infec-tions/AIDSoutpatientclinic and atthegeriatric outpatient clinic ofthe Santa Casade Misericórdia, a university teach-ing hospital in Vitória city, Brazil between December 2013 andJuly2014.ThesampleconsistedofHIV-infected individ-ualsof50yearsofageormoreunderantiretroviraltherapy (ART)and HIV-uninfected individuals of60 yearsof ageor more. Individuals with neurological diseases, chronic pul-monarydisease,partialparalysis,oranyothermorbiditythat couldaffecttheirphysicalperformancewereexcludedfrom thestudy.Thestudyprotocol wasapprovedbytheinternal review board of the Escola Superior de Ciências da Saúde da SantaCasadeMisericórdiadeVitória(EMESCAM)under refer-enceCAAE:09180512.9.0000.5065.Allparticipantssignedan informedconsentform.
A bioelectrical impedance scale (InBody 520 device; BiospaceInc.,BeverlyHills,CA, USA)wasused toevaluate musclemass.Thereproducibilityofthismethodisgoodandit representsanacceptablealternativetothegoldstandardtests, magneticresonanceimaginganddual-energyX-ray absorp-tiometry(DXA).9UsingtheJanssenequation,thenormalized
skeletal muscleindex (SMI)(absolute musclemass in kilo-grams/squared height in meters) was calculated. SMI was definedaslowwhenvalueswere≤10.75formenand≤6.75 forwomen.3,10
Muscle strength was evaluated using a Jamar hydraulic handdynamometer(SammonsPreston,Bolingbrook,IL,USA). The arithmetic mean of three measurements taken with the dominant hand was calculated and then adjusted for body mass index (BMI).3 Muscle strength was considered
reduced under the following conditions for men: BMI≤24 andstrength≤29kg;BMIfrom24.1to28andstrength≤30kg; BMI>28 and strength≤32kg. The parameters for women were:BMI≤23andstrength≤17kg;BMIfrom23.1to26and
strength≤17.3;BMIfrom26.1to29andstrength≤18kg,and BMI>29andstrength≤21kg.11Theseparameterswere
previ-ouslydefinedandvalidatedbytheEuropeanworkinggroup onsarcopeniainolderpeople.12
Physicalperformancewasevaluatedaccordingtothegait speed testinwhichthepatientisaskedtowalkadistance of4m inamaximum time of5s,with performancebeing consideredimpairedwhenspeedislessthan0.8m/s3.
InaccordancewiththeEWGSOPdefinitions,lowSMIasan isolated findingcharacterizedpresarcopenia.Theassociation oflowSMIwitheitherlowmusclestrengthorpoorphysical performancewasconsideredsarcopenia,whileareductionin allthreecriteriawasclassifiedasseveresarcopenia.3
The continuousvariables were described as means and standard deviations, whilethedichotomous variables were described as percentages. Student’s t-test for independent samplesandchi-squaretestorFisher’sexacttestwereused forgroupcomparison.Binarylogisticregression,either unad-justedoradjustedforageandBMI,wasusedtopredictthe likelihoodofassociationwithsarcopenia.Thestatistical sig-nificanceofthecontributionofthepredictorsintheregression model was determined using the Waldtest. p-values<0.05 wereconsideredstatisticallysignificant.TheSPSSstatistical softwareprogram,version22.0wasusedthroughoutthe anal-ysis.
The study was conducted over a 6-month period and included 93 individuals. Of these, 33 were HIV-infected patientsonART.In30(90.9%)ofthosepatients,viralloadwas undetectable.Inrelationtogender,42.42%werewomenand 57.58%men.Meanagewas59±7years(range50–78years)and meanBMIwas25±6kg/m2(range17.7–52.4kg/m2).Ofthe60
HIV-uninfectedcontrols,71.7%werewomenand28.3%men. Meanagewas70±7years(range60–87years)andmeanBMI was28±6kg/m2(range15.3–41.6kg/m2).
BasedontheEWGSOPdiagnosticcriteriaforsarcopenia,52 individualsintheHIV-uninfectedcontrolgroup(86.7%)were normal,4(6.7%)hadpresarcopeniaand4(6.7%)had sarcope-nia.IntheHIV-infectedgroup,21(63.6%)werenormal,while 4 (12.1%)had presarcopenia, and 8(24.2%) had sarcopenia (Table1). Presarcopeniawas 3.71(95% CI:1.32–10.38)times morecommon inthe HIV-infectedgroupinrelation tothe controlgroup.AfteradjustingforageandBMI,thisriskratio increasedto3.90(95%CI:1.38–10.95).Theriskofsarcopenia was 4.95 (95% CI:1.34–18.23) timeshigher forHIV-infected individualscomparedtotheHIV-uninfectedcontrols. Follow-ing adjustmentforageandBMI,thisriskratioincreasedto 5.20(95%CI:1.40–19.20),asshowninTable2.
The study group was younger and mostly male reflect-ing the composition of the HIV outpatient clinic whereas the control group was older and mostly female reflecting the composition ofthe outpatientgeriatric clinic,as those
Table1–Frequencyofpresarcopeniaandsarcopeniainthestudysample.
Normal Presarcopenia Sarcopenia Total HIV-uninfectedn(%) 52(86.7%) 4(6.7%) 4(6.7%) 60(100%) HIV-infected n(%) 21(63.6%) 4(12.1%) 8(24.2%) 33(100%) Total n(%) 73(78.5%) 8(8.6%) 12(12.9%) 93(100%)
braz j infect dis.2016;20(1):99–102
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Table2–Unadjustedandadjustedbinarylogisticregressionanalysis.
Unadjusted p-value AdjustedforageandBMI p-value Presarcopenia HIV-uninfected 1 0.01 1 0.01 HIV-infected 3.71(1.32–10.38) 3.90(1.38–10.95) Sarcopenia HIV-uninfected 1 0.01 1 0.01 HIV-infected 4.95(1.34–18.22) 5.20(1.40–19.20)
individuals were consecutivelyrecruited forthe study pro-tocol. As sarcopenia is more common in women than in men, and in older people than younger, we should have expected greater frequency of sarcopenia in the control groupbut the resultshaveshown the opposite, even after adjustment bymultivariate analysis. Unfortunately, as the samplewassmall,itwasnotpossibletostratifythe differ-entgroupsforgender.Thepatientsinthestudygroupwereon antiretroviraltherapyfor7.15±3.74years.Themainbackbone wasLamivudine–Zidovudineusedby17patientsfollowedby Lamivudine–Tenofovir in 16 patients. The third drug used was Efavirenz in13 patients, followed byritonavir-boosted Atazanavirin8,ritonavir-boostedlopinavirin8,nevirapinein 2,andritonavir-boosteddarunavirintheremaining2patients. Thesefindingsrevealastrongpositiveassociationof pre-sarcopeniaandsarcopeniawithHIVinfectioninpatientswith ameanageof59yearsandonregularuseofART,mostwith anundetectableviralload,comparedtoanuninfectedgroup ofolderindividualswithameanageof70±7yearsofage. Althoughthe meanageandgenderdistributionofpatients that composethe two outpatient groupswere not equiva-lent, that makes indeed stronger the association between HIVinfection andsarcopenia.Yarasheskietal.conducteda longitudinalstudyandreportedsimilarratesofskeletal mus-clemass loss inan HIV-infected groupand inthe control group;however,thoseinvestigatorsfailedtoevaluatemuscle strengthandfunction.13
The present frequencies of presarcopenia and sarcope-nia found for the HIV-infected patients (12.1% and 24.2%, respectively)were comparableto the ratesof 20%and 5%, respectively,foundinacross-sectionalstudywithasample ofHIV-infectedindividuals.Inbothstudies,ahighriskof sar-copeniaininfectedindividualswasevident.11
Recently,Reesetal.reportedaprevalenceoffrailtyof19% in122HIV-infectedpatientsevaluatedusingthe5-component Friedfrailtycriteria.Themostcommoncriteriawere depres-sionand lowphysicalactivity.Curiously,theleastcommon werethemarkersofsarcopenia,leadingtheauthorsto con-clude that frailty in HIV-infectedindividuals is potentially reversible.14Önenetal.evaluatedalargergroupof445
HIV-infectedpatientswithameanageof41.7yearsandreported a prevalence of frailty of 9%, which was associated with comorbiditiesandmoreadvancedimmunodeficiency.15 The
introduction ofART was foundto exerta protectiveeffect againstfrailtyinthefollow-upoftheMulticenterAIDSCohort StudyintheUnitedStates.16
Wassermanetal.alsoreportedahighprevalenceoflow musclemass(between18.8and21.9%dependingonthe def-initionused) inmidlife and olderHIV-infected individuals, particularlymales,despiteCD4cellreconstitutionandviral
suppression.11 Several investigators have shown that
HIV-infectedpatientsexperiencealossofbonemassandhavea greaterriskoffragilityfractures.6,17Untilrecently,the
princi-palfocushasbeenonpreventingandmanagingbonedisease inHIV/AIDS.18Nevertheless,musclemasslosshasbegunto
attracttheattentionofhealthcareproviders,andtheremay beacorrelationwithbonemassloss.Thismayconstituteone moreriskfactorforpatientswithHIV/AIDS.19
There are some clear limitations associated with the presentstudy,particularlywithreferencetothesmall sam-plesizeandtheconsequentlackofstatisticalpowertodetect differences when comparing the frequency of sarcopenia betweenmalesandfemalesorthelossofmusclemasswith the use ofdifferent antiretroviral drugs. Nevertheless, the presentresultsshowapositiveassociationofsarcopeniain HIV-infectedindividuals.Thisassociationremainedpositive evenwhencomparedwithanoldergroupandafter control-lingfortheeffectofageandBMI,thusconstitutingonemore componentintheriskoffallsandfracturesintheaging HIV-infectedpopulation.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgements
Dr Alvaro Armando Carvalhode Moraeswho helped with bioimpedancemeasures,andCNPQandFAPESforfundingthis research.
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