Effects of aerobic and resistance exercise alone or combined on strength and hormone outcomes

21 Pages·2017·2.31 MB·English

RESEARCHARTICLE
Effects of aerobic and resistance exercise
alone or combined on strength and hormone
outcomes for people living with HIV. A meta-
analysis
CamiloGerma´nAlbertoPe´rezChaparro1*,PhilippZech2,FelipeSchuch3,
BerndWolfarth4,MichaelRapp2,AndreasHeiβel2
a1111111111 1 UniversityOutpatientClinic–CenterforSportsMedicine,DepartmentSports&HealthSciences,University
ofPotsdam,Potsdam,Brandenburg,Germany,2 SocialandPreventiveMedicine,DepartmentExerciseand
a1111111111
HealthSciences,UniversityofPotsdam,Potsdam,Brandenburg,Germany,3 Post-graduateProgramin
a1111111111
HealthandHumanDevelopment,LaSalleUniversity,Canoas,RS,Brazil,4 DepartmentofSportsSciences,
a1111111111
DivisionofSportsMedicine,HumboldtUniversita¨tzuBerlin,Berlin,Germany
a1111111111
*[email protected]
Abstract
OPENACCESS
Citation:Pe´rezChaparroCGA,ZechP,SchuchF,
WolfarthB,RappM,HeiβelA(2018)Effectsof Background
aerobicandresistanceexercisealoneorcombined
onstrengthandhormoneoutcomesforpeople Infectionwithhumanimmunodeficiencyvirus(HIV)affectsmusclemass,alteringindepen-
livingwithHIV.Ameta-analysis.PLoSONE13(9): dentactivitiesofpeoplelivingwithHIV(PLWH).Resistancetrainingalone(RT)orcombined
e0203384.https://doi.org/10.1371/journal.
withaerobicexercise(AE)islinkedtoimprovedmusclemassandstrengthmaintenancein
pone.0203384
PLWH.Theseexercisebenefitshavebeenthefocusofdifferentmeta-analyses,although
Editor:BelindaParmenter,UNSWSydney,
onlyalimitednumberofstudieshavebeenidentifieduptotheyear2013/4.Anup-to-date
AUSTRALIA
systematicreviewandmeta-analysisconcerningtheeffectofRTaloneorcombinedwith
Received:February12,2018
AEonstrengthparametersandhormonesisofhighvalue,sincemoreandrecentstudies
Accepted:August20,2018 dealingwiththesetypesofexerciseinPLWHhavebeenpublished.
Published:September4,2018
Copyright:©2018Pe´rezChaparroetal.Thisisan Methods
openaccessarticledistributedunderthetermsof
RandomizedcontrolledtrialsevaluatingtheeffectsofRTalone,AEaloneorthecombina-
theCreativeCommonsAttributionLicense,which
tionofboth(AERT)onPLWHwasperformedthroughfiveweb-databasesuptoDecember
permitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginal 2017.RiskofbiasandstudyqualitywasattainedusingthePEDroscale.Weightedmean
authorandsourcearecredited. difference(WMD)frombaselinetopost-interventionchangeswascalculated.TheI2statis-
DataAvailabilityStatement:Allrelevantdataare ticsforheterogeneitywascalculated.
withinthepaperanditsSupportingInformation
files.
Results
Funding:ThisworkwassupportedbyIntramural
juniorresearchgroupgrantfromtheUniversityof Thirteenstudiesreportedstrengthoutcomes.Eightstudiespresentedalowriskofbias.The
PotsdamtoAndreasHeißel.PhilippZechwas overallchangeinupperbodystrengthwas19.3Kg(95%CI:9.8–28.8,p<0.001)after
partlyfundedbyascholarshipfromtheFrankfurter
AERTand17.5Kg(95%CI:16–19.1,p<0.001)forRT.Lowerbodychangewas29.4Kg
AllgemeineZeitung.CamiloPe´rezwasfundedby
(95%CI:18.1–40.8,p<0.001)afterRTand10.2Kg(95%CI:6.7–13.8,p<0.001)forAERT.
theCOLFUTURO-DAADscholarship.Thefunders
hadnoroleinstudydesign,datacollectionand Changeswerehigheraftercontrollingfortheriskofbiasinupperandlowerbodystrength
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EffectsofexerciseonPLWHstrengthandhormones:Ameta-analysis
analysis,decisiontopublish,orpreparationofthe andforsupervisedexerciseinlowerbodystrength.Asignificantchangetowardslowerlev-
manuscript. elsofIL-6wasfound(-2.4ng/dl(95%CI:-2.6,-2.1,p<0.001).
Competinginterests:Theauthorshavedeclared
thatnocompetinginterestsexist. Conclusion
Abbreviations:95%CI,95%Confidenceinterval; Bothresistancetrainingaloneandcombinedwithaerobicexerciseshowedapositive
AE,Aerobicexercise;AERT,Aerobicexercise
changewhenstudieswithlowriskofbiasandprofessionalsupervisionwereanalyzed,
combinedwithresistancetraining;AH,Andreas
Heissel;BMD,Bonemineraldensity;CP,Camilo improvingupperand,morecritically,lowerbodymusclestrength.Also,thisstudyfoundthat
Pe´rez-Chaparro;ART,Combinedanti-retroviral exercisehadaloweringeffectonIL-6levelsinPLWH.
drugtherapy;MeSH,CombinedMedicalSubject
Headings;CG(s),ControlGroup(s);EC,Eligibility
Criteria;I2,Heterogeneity;HIV,Human
immunodeficiencyvirus;IL-1β,Interleukin1β;IL-6,
Interleukin6;IQR,Interquartilerange;IG(s),
Interventiongroup(s);kg,Kilograms;HR , Introduction
max
Maximumheartrate;μg/ml,Microgramsper
AccordingtotheJointUnitedNationsProgramonHIV/AIDS,17millionpeoplelivingwith
milliliter;mmol/l,Millimolesperliter;cells·ml-1,
HIV(PLWH)receiveanti-retroviraldrugtherapyworldwide[1].Thisisnoteworthybecause
Numberofcellspermicroliter;n,Numberof
studies/participants;PLWH,PeoplelivingwithHIV; earlyuseofcombinedanti-retroviraldrugtherapy(ART)hasbeenshowntoincreaselife
PZ,PhilippZech;pg/dl,Picogramsperdeciliter; expectancyby~43.1years[2].Thus,humanimmunodeficiencyvirus(HIV)haschanged
lbs,Pounds;PRISMA,PreferredReportingItems fromanacuteandfataldiseaseintoachronicdiseasethatcomprisesagreaterproportionof
forSystematicReviewsandMeta-Analyses;RCTs,
personsolderthan50years[3].
Randomizedcontrolledtrials;RT,Resistance
Humanimmunodeficiencyvirus(HIV)infectionaffectsnotonlytheimmunesystem[4],
trainingalone;SD,Standarderror;WMD,Weighted
meandifference. butalsothemusculoskeletalsystem.Inparticular,PLWHpresentpre-sarcopeniaorsarcope-
nia[5].OtherassociatedmuscleproblemslikemyalgiaaretwiceascommonamongPLWH,
withorwithoutreceivingARTtreatment[6].Lowbonemineraldensity(BMD)isalsodirectly
affectedbyHIVinfection,duetothevirusand/oruseofART,whichstimulatesosteoclastic
activityanddecreasesosteoblastactivity,affectingBMDinnaiveARTpeople[7].These
changestothemusculoskeletalsystemmaybemediatedbychangesininterleukins,cortisolor
testosterone[8–10]andresultinadecreasedcapacitytocarryoutactivitiesofdailylife[11].
Resistanceexercisetrainingbothalone(RT)andcombinedwithaerobicexercise(AERT)is
linkedtoimprovedBMD[12],musclemassandstrengthmaintenance,complementedby
weightgain[13–15]andfewerepisodesoffalls[16]inthegeneralpopulation.Theseexercise
benefitsinPLWHhavebeenthefocusindifferentsystematicreviewsandmeta-analyses[17–
21].GomesNetoetal.[18]showedanimprovement(WMD=25.1kg,p<0.001)inkneeexten-
sormusclestrength(n=2studies)afterAEintervention.ThisfindingisinlinewiththoseofO
´Brienetal.’s[20,21]meta-analysisshowingasignificantimprovement(WMD=10.5kg1-RM,
p<0.001)inkneeflexionstrength(n=3studies)afterAERTintervention.However,O´Brien
etal.´s[20,21]reportedanon-significantimprovementinotherlowerextremitymusclegroups
throughresistancetrainingcombinedwithaerobicexercise.Subgroupanalyseswereonlyper-
formedbyO-Brienetal.[21]dealingwithtestosteronesupplementation,withanon-significant
improvementinkneeflexion/extensionstrength(n=2studies).Nevertheless,theseresultsneed
tobeinterpretedcarefullybecauseofthelownumberofinvestigatedstudies.Also,previous
studies[22–24]havesuggestedthatthelengthoftheinterventionandsupervisionbyexercise
professionalsmaymoderatethebenefitsofexerciseonphysicalandmentalhealthoutcomes.
However,noneofthepreviousmeta-analyseshaveinvestigatedwhetherornotlongerinterven-
tionsandthesupervisionofexercisemodifytheeffectsofexerciseonPLWH.
Thissystematicreviewandmeta-analysisexploredtheeffectsofexerciseonbodystrength
andhormonallylevelsinPLWHafterresistancealoneorcombinedwithaerobicexercise
intervention.Likewise,otherphysiologicalparameters(i.e.cortisol,testosterone)relatedto
strengthandHIVwereanalyzed.Thisisofimportanceinthissystematicreview,sinceno
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EffectsofexerciseonPLWHstrengthandhormones:Ameta-analysis
meta-analyseshaveaddressedthismattertodate.Finally,subgroupanalysisforeachexercise
intervention,upperandlowerbodymuscles,professionalsupervisionofexercise,performing
morethan150minutesofexerciseperweek,andcontrollingforactivecontrolgroupsand
high-qualitystudies(PEDroscore(cid:21)5)wereconductedincompliancewiththeCochrane
meta-analysisstandards.
Methods
Thissystematicreviewandmeta-analysiswasregisteredinthePROSPEROinternationalpro-
spectiveregisterofsystematicreviews(CRD42018087004)andperformedfollowingtheguide-
linesofthePreferredReportingItemsforSystematicReviewsandMeta-Analyses(PRISMA)
[25].
Eligibilitycriteria
Randomizedcontrolledtrials(RCTs)comparingresistancetrainingalone,aerobicexercise
aloneoraerobicexerciseincombinationwithresistancetrainingagainstanon-exercisingcon-
trolgroup(CG)wereconsideredforinclusion.Thestudieshadtoincludeparticipantswith
HIVatanystageoftheinfectionprocess,olderthan18years,withorwithoutco-morbidities,
andinvestigatestrengthoutcomes(liftedexternalresistanceinkgorlbs)astheprimaryout-
comeandhormones(i.e.testosterone)relatedtothemuscularsystemassecondaryoutcomes,
inresponsetoexercise.AerobicexercisewasdefinedaccordingtotheAmericanCollegeof
SportsMedicine(ACSM)as“anyactivitythat:useslargemusclegroups,canbemaintained
continuously,andisrhythmicinnature”[26],andresistancetrainingwasoutlinedas“aform
ofphysicalactivitythatisdesignedtoimprovemuscularfitnessbyexercisingamuscleora
musclegroupagainstexternalresistance”[27].Bothexerciseshadtobeperformedmorethan
twotimesperweekasdescribedbyGomesNetoetal.[18]ratherthanthreetimesperweekas
inO´Brienetal.[21],andforatleastfourweeks.Studiesadministeringsteroidsupplementa-
tiontotheIGsand/orCGswereexcludedduetothepossibilityofanadditionaleffectonmus-
clestrength.Otherformsofexercise(e.g.taichi,qigong)werenotconsideredbecausetaichi
interventionsvariedinthetaichipracticedforms[28]andhomogeneityamongthetypesof
exerciseperformedbytheIGsneededtobeachieved.
Studiesinvestigatingtwoexercisinggroupswithoutanynon-exercisingcontrolgroups
wereconsideredtobeexcludedbecauseanexercisingcontrolgroupcouldleadtoasignificant
improvementinmusclestrength,resultinginadecreasedabilityoftheinterventiongroup
(IG)todemonstrateminimalchanges.Notnecessarilyphysicalactivities(placebo-treated,
socialcontactexerciserecommendations,counseling,recreationalactivities)andverylight
physicalactivitygroups,wereconsideredtobeactiveCGs.Groupsfollowingtheirusualactiv-
ityandexplicitlynotexercisingwereconsideredtobepassiveCGs.
Literaturesearchstrategyforstudyidentification
Aliteraturesearchwasperformedusingfivedatabases(clinicaltrials.gov,PEDrophysiotherapy
evidencedatabase,PubMed,theCochraneCentralRegisterofControlledTrials(CENTRAL)
andWebofScience),restrictedtoEnglish-languagestudiespublisheduptotheendofDecem-
ber2017.Tworeviewers(CPandPZ)individuallyscreenedandrecordedtherelevantcitations
followingtheaboveeligibilitycriteriaandrecordedtheminastandarddataformat.After
selectingtherelevantcitationsbytitle,theabstractswerescreened.Afterfulfillingbothprevi-
oussteps,fulltextswereobtainedandevaluated.Incaseofdisagreement,bothauthorsdis-
cussedtheirdifferencesuntilreachinganagreement.Ifthiswasnotpossible,athirdauthor
(AH)wasconsultedtodeterminethefinaldecision.
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EffectsofexerciseonPLWHstrengthandhormones:Ameta-analysis
Searchparametersandsyntaxwereadaptedtoeachdatabase’srequirements.Textwords
andCombinedMedicalSubjectHeadings(MeSH)termswererelatedtoexerciseandphysio-
logicalparameters.ThesearchstrategyispresentedinTable1.
Datacollection
Datawasextractedbybothreviewers(CPandPZ)independently,usingastandarddigital
sheetform.
Measuringunitswereindependentlyconvertedbythetworeviewers(CPandPZ),pounds
(lbs)tokilograms(kg)andmmol/ltopg/dl.OutcomesreportedasMean±standarderroror
Meanchange(postminuspre)±standarderrorwereconvertedintomean±standard
deviation.
Incaseofmissingrelevantdataintheselectedstudies,theoriginalauthorswerecontacted
viaemailaskingfortherequiredmissinginformation.Iftwoweekspassedwithoutananswer
fromtheauthor,theauthorwaskindlyremindedandtheco-authorswerecontactedviaemail.
Iftheauthordidnotanswerouremails,thenthestudywasleftoutofthequantitative
synthesis.
Riskofbiasandqualityofincludedstudies
CPandPZindividuallyassessedtheriskofbiasandthequalityoftheincludedstudiesusing
thePEDroscale[25,29].EveryPEDrocriterionhadtobeclearlymetanddescribedinthe
selectedstudy.ThePEDroscaleconsistsofelevencriteriainwhichthefirst“criterionofeligi-
bility”ismarkedwitha“yes”or“no.”Ifthestudyhadnoeligibilitycriteria,thestudywas
excluded.Therestofthecriteriaweremarkedwithacheckmarkora“0.”ThepossiblePEDro
scorerangeisfrom0to10.Discrepanciesonthestudies’PEDroscorebetweenthetworeview-
erswereresolvedbyathirdauthor(AH).Theresultsofthequalityandriskofbiasassessment
oftheincludedarticlesareshowninTable2intheResultssection.
StudieswithaPEDroscore(cid:21)5wherecategorizedashigh-qualitystudies,becauseblinding
mightbedifficulttoachieveandmaintainforvariousreasonsandislessfrequentlyreported
innon-pharmacologicaltreatmentRCTs[30,31].Moreover,Moseleyetal.[32]investigated
thenumberofRCTsavailableinthePEDrodatabasethatsatisfiedtheblindingcriteria(subject
blinding,therapistblindingorassessorblinding)andfoundalowprevalenceofblinding,with
5%usingblindedtherapists,9%blindedsubjectsandonly34%blindedassessors.Forthese
Table1. Systematicsearchstrategy.
Database CombinedMeSHtermsandtextwords
PubMed (HIV)OR(humanimmunodeficiencyvirus)AND(exerciseORexercisetherapy
ORphysicalactivityORaerobicexerciseORresistancetraining)AND(hormone
ORtestosteroneORcardiovascularORstrengthORfitnessORphysiological)
AND(randomizedcontrolledtrialORrandomizedORclinicaltrials)
Cochranelibrary ("HIV"OR"humanimmunodeficiencyvirus")AND("exercise"OR"physical
activity"OR"aerobicexercise"OR"resistancetraining"OR"exercisetherapy")
AND("hormone"OR"testosterone"OR"cardiovascular"OR"strength"OR
"fitness"OR"physiological"AND"randomizedcontrolledtrial")
Clinicaltrials.gov (HIVinfectionHIVANDexerciseANDphysiologicORmuscle)and(HIVAND
exerciseANDcardiovascular)
PEDrophysiotherapyevidence (HIVexercisemuscle)or(HIVexercisecardiovascular)or(HIVexercise
database hormones)
WebofScience (HIVANDexercise)
https://doi.org/10.1371/journal.pone.0203384.t001
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EffectsofexerciseonPLWHstrengthandhormones:Ameta-analysis
Table2. PEDroscale,qualityassessmentofincludedtrialsinthesystematicreview.
Study EC I II III IV V VI VII VIII IX X Total
AginD.2001 Y ✓ ✓ ✓ 0 0 0 0 0 ✓ ✓ 5
BhasinS.2000 Y ✓ 0 ✓ 0 0 ✓ 0 ✓ ✓ ✓ 6
DolanS.2006 Y ✓ 0 ✓ 0 0 0 ✓ ✓ ✓ ✓ 6
DudgeonWD.2012 Y ✓ 0 ✓ 0 0 0 0 0 0 ✓ 3
FarinattiPT.2010 Y ✓ 0 ✓ 0 0 ✓ ✓ ✓ ✓ ✓ 7
FitchK.2012 Y ✓ 0 ✓ 0 0 ✓ 0 ✓ ✓ ✓ 6
GrinspoonS.2000 Y ✓ 0 0 0 0 0 0 0 ✓ ✓ 3
LoxCL.1995 Y ✓ 0 0 0 0 0 ✓ 0 ✓ ✓ 4
LoxCL.1996 Y ✓ 0 0 0 0 0 ✓ 0 ✓ ✓ 4
MendesEL.2013 Y ✓ 0 0 0 0 0 0 0 ✓ ✓ 3
Pe´rez-MorenoF.2007 Y ✓ ✓ ✓ 0 0 ✓ 0 0 ✓ ✓ 6
ShahKN.2016 Y ✓ ✓ ✓ 0 0 ✓ ✓ 0 ✓ ✓ 7
ZanettiHR.2016 Y ✓ 0 ✓ 0 0 0 ✓ 0 ✓ ✓ 5
EC,eligibilitycriteria;I:allocatedrandomizationofsubjectstogroups;II:concealedallocation;III:similaritiesofgroupsatbaseline;IV:blindingofsubjects;V:blinding
ofresearchers/evaluators;VI:blindingofassessors;VII:measureofatleastonekeyoutcomeobtainedfrommorethan85%ofsubjectsinitiallyallocatedtogroups;VIII:
intentiontotreat;IX:comparisonresultsbetweengroups;X:measuredatleastonekeyoutcomeattwotimepoints;✓,criterionispresentotherwise;0,criterionis
missing.
https://doi.org/10.1371/journal.pone.0203384.t002
reasons,thetotalPEDroscoreforRCTsinvolvingexerciseinterventionscanbeaffectedand
thusaPEDroscorelowerthansixcanbeattainedeveniftheothercriteriaaresatisfied.
Statisticalanalysis
Therandomeffectmodel[33,34]wasusedtocalculatetheweightedmeandifference(WMD)
betweeninterventionandcontrolgroupchangesfrombaselineandpost-intervention.When
thechangewasnotavailable,thechange(meanpre-interventionminusmeanpost-interven-
tion)andthestandarddeviationaccordingtotheCochranhandbookforsystematicreviews
ofinterventions[35]werecalculated.Parameterswereanalyzedforupperandlowerbody
strengthaswellashormones.Subgroupanalyseswereperformedforresistancetraining(RT)
alone,aerobicexercisecombinedwithresistancetraining(AERT),upperandlowerbodymus-
cles,professionalsupervisionofexercise,performingmorethan150minutesofexerciseper
week,excludingactiveCGs,preART-era,andhigh-qualitystudies(PEDroscore(cid:21)5)[23].A
pvalueequaltoorlessthan0.05wasconsideredsignificant.Interpretationoftheeffectsize
wasdonewiththemostcommonlyusedcut-offdefinedbyCohen[36],d=.20small,.50
mediumand.80large.
Totestforheterogeneity,theI2statisticsand95%CI[37]wascalculated.Valuesbetween
25–50%reflectlow,50%-75%moderate,andvaluesgreaterthan75%reflecthighheterogeneity
[37].Toexploretheheterogeneity,thismeta-analysislookedfordifferencesacrosssubgroups
bycalculatingtheChisquare(Χ2).Publicationbiaswasassessedbytheegger´stest[38].All
analyseswereperformedusingReviewManagerVersion5.3[39].
Results
Searchdescriptionofselectedstudies
Atotalof398citationsthroughthesearchcriteriafromthedatabasesdescribedintheMethods
sectionwhereretrieved.Afterscreeningthetitles,231citationswereexcludedduetoineligible
focus.Oftheremaining167studies,50wereexcludedforthefollowingreasons:exercisewas
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EffectsofexerciseonPLWHstrengthandhormones:Ameta-analysis
performedbythecontrolgroup(n=9),thelanguagewasotherthanEnglish(n=4),theinter-
ventionorcontrolgroupswerepartiallyortotallyintegratedwithHIVseronegativepartici-
pants(n=6),thesearchedoutcomeswerenotaddressed(n=11),orthecitationsreferredto
non-RCTs(n=13)orreviews(n=7).Theremaining117citationswerescreenedbeforefull
textswereacquired;66citationswereduplicates.51studies’fulltextswerereadand17studies
hadtobeexcluded:inonestudy,theinterventiongroupsperformedonlyoneboutofexercise
[40],onestudy’scontrolgroupperformedexercise[41],twostudiesdidnotinvestigateexer-
cise[42,43],twostudies’interventionorcontrolgroupswerepartiallyortotallyintegrated
withHIVseronegativeparticipants[44,45],fivestudiesdidnotinvestigatethedesiredout-
comes[46–50],fivewerenotRCTs[51–55]andonestudyadministerednandrolone[56].In
total,34studiesfromthesystematicsearchandfourstudiesaddedbycross-referencingcita-
tionsmettheeligibilitycriteriaandwereconsideredrelevantforinclusioninthemeta-analy-
sis.Intotal,13studiesreportedstrengthoutcomesandwereincludedinthequantitative
analysis.Ofthese,fourstudies[57–60]reportedstrengthandhormoneoutcomes(SeeFig1).
Characteristicsofstudiesexcludedfromquantitativesynthesis
Followingoursearchstrategy,fivestudies[61–65]wereexcludedduetoincompletedataor
becausetherequesteddatawasnotavailable.SeeexcludedstudiesinS1Table,Informationon
excludedandincludedstudies.
Descriptionofthestudiesincludedinthemeta-analysis
Ofthe13includedstudies,eightstudies[57,60,66–71]wereclassifiedashigh-qualitystudies
(seeTable2),fourstudiesinvestigatedRT[57,60,66,72]andeightstudiesAERT[58,59,67–
71,73].ThestudiesofLoxetal.[74]and[72]sharedthesametwointerventiongroupsand
results:onegroupperformedAEaloneandtheotherRTalone,withtheexactsamenumberof
controlgroupparticipantsinbothstudies.Thus,forthepurposeofanalysiswedecidedto
treatLoxetal.[74]asanAE-onlyinterventionandLoxetal.[72]asanRT-onlyintervention.
PassiveCGswereidentifiedinsixstudies[58,60,67,68,71,73]andonewithnolifestylemodifi-
cation[71].SevenstudieshadactiveCGs,threestudiesCGsperformedverylow-intensity
physicalactivitylikewalkingorstretching[70,72,74],onestudy[66]appliedproteinsupple-
mentation1g(cid:1)kg-1(cid:1)day-1totheCG,andthreestudies[57,59,69]administeredtestosteronepla-
ceboinjectionstotheCGs.CharacteristicsofalltheincludedstudiescanbeseeninS1Table.
Characteristicsofstudiesincludedinthemeta-analysis
Thenumberofparticipantsincludedinthe13studieswerefortheinterventiongroupn=249
atbaselineandn=246post-intervention,whereasforthecontrolgroupn=1216atbaseline
andn=210attheendofthestudy.Eightstudieshadameandropoutrateof10.7±12.1%.
Twostudiesreportednodropouts[60,68]andthreestudies[72–74]onlyreportedparticipants
whocompletedthestudy.Themeanageforthecontrolgroupwas42±5.7yearsandforthe
interventiongroup42.9±5.3years.Fivestudies[60,66,67,69,71]included42womeninthe
controlgroupand41womenintheinterventiongroup.Sevenstudiesrecruitedonlymalesub-
jects[57–59,68,70,72,74].OnlythestudybyMendesetal.[73]didnotreporttheageandgen-
deroftheparticipants.TheaveragebaselineCD4cellcountwasreportedin12studies[57–
60,66–72,74].FortheCGswas432.2±147.9cellsμl-1andfortheIGs431.5±167cellsμl-1.
Fivestudiesincludedparticipantswithhealth-relatedconditionsasidefromHIV[57,67,69–
71].TwostudiesincludedparticipantswithAIDSwastingsyndrome[57,59],onestudylipody-
strophy[67],onestudylowtestosteronelevels[57],twostudiesmetabolicdiseases[69,71]and
onestudyincludedparticipantswithfunctionallimitations[71].
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EffectsofexerciseonPLWHstrengthandhormones:Ameta-analysis
Fig1.SearchandselectionofstudiesfromthesystematicreviewaccordingtoPRISMA.PhysiotherapyEvidenceDatabase(PEDro),Preferred
ReportingItemsforSystematicReviewsandMeta-Analyses(PRISMA).
https://doi.org/10.1371/journal.pone.0203384.g001
Ninestudiesreportedstrengthoutcomeswithouthormoneoutcomes[66–74].Twostudies
[57,59]reportedstrengthoutcomesandtestosterone.Threestudies[57–59]reportedstrength
outcomesandfreetestosterone.ThestudybyDudgeonetal.[58]reportedstrengthoutcomes,
cortisolandinsulin-likegrowthfactor1(IGF-1).Twostudies[58,60]reportedstrengthout-
comesandpro-inflammatoryinterleukins(IL-6andIL-1β).ThestudybyFitchetal.[69]
reportedstrengthoutcomesandc-reactiveprotein(CRP).Long-termeffects(>4months)of
exercisewereidentifiedonthree[66,69,73]ofthe13includedstudies.
The1-RMtestusedtomeasuremusclestrengthwasreportedinsixstudies
[57,60,66,67,69,73]andthepeakisometricforcetestwasusedinthreestudies[59,72,74].Char-
acteristicsofalltheincludedstudiescanbeseeninS1Table.
Riskofbias
Accordingtotheriskofbiasanalysis,eightstudiesscored(cid:21)5inthePEDroscale,specifyinga
lowriskofbias.FivestudiespresentedahighriskofbiaswithaPEDroscore<5.SeeTable2.
ChangesonbodystrengthinPLWH
Alltypesofrepetitionmaximum(1-RM,3-RM,6-RMand12-RM)wereincluded.Nodetails
onthetypeofmachineusedtoperformtheRMtestwasmentionintheincludedstudies.See
S1Table.
Twooverallmeta-analyses(seeFigs2and3)and34subgroupanalyseswereperformed.
TheoverallchangeafterinterventiononupperbodystrengthinPLWHfrombaselinewas18
kg(95%CI:11.2–24.8,p<0.001)favoringtheIG.Lowerbodystrengthalsoincreasedby16.8
kg(95%CI:13–20.6,p<0.001)favoringtheIG.Sub-analysisrevealedasignificantincreaseon
liftedweightforeachmusclegroup,favoringtheIG.Afterlong-termexercise,IGupperbody
strengthshowedasignificantchange13.7kg(95%CI:6–21.5,p<0.001).Thiswasalsotrue
forIGlower-bodystrengthwithameanchangeof16kg(95%CI:11.6–20.4,p<0.001),but
significantchangeswereonlyforlegflexionandextensionlong-termexercisemusclegroups
(SeeTable3).
Fig2.UpperbodystrengthchangesafterexerciseinPLWH.Standarddeviation(SD),total(nparticipants),95%
confidenceinterval(95%CI),Z-score(Z),significance(p).
https://doi.org/10.1371/journal.pone.0203384.g002
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EffectsofexerciseonPLWHstrengthandhormones:Ameta-analysis
Fig3.LowerbodystrengthchangesafterexerciseinPLWH.Standarddeviation(SD),total(nparticipants),95%
confidenceinterval(95%CI),Z-score(Z),significance(p).
https://doi.org/10.1371/journal.pone.0203384.g003
EightstudieshadaPEDroscore(cid:21)5.Thissub-analysisrevealedagreaterchangeinIG
upperbodystrengthof22.6kg(95%CI:12.5–32.7,p<0.001)and20.1kg(95%CI:14.7–25.4,
p<0.001)forlowerbodystrength,comparedtothetwomainmeta-analyses.
AerobicexercisecombinedwithresistancetrainingpromptedagreaterchangeinIGupper
bodystrengthof19.3kg(95%CI:9.8–28.8,p<0.001)comparedtoRTalone,wherethe
changewasonly17.5kg(95%CI:16–19.1,p<0.001).Incontrast,RTaloneprovokedahigher
changeinIGliftedlowerbodyweightby29.4kg(95%CI:18.1–40.8,p<0.001),whilethe
changeinaerobicexercisecombinedwithresistancetrainingwasonly10.2kg(95%CI:6.7–
13.8,p<0.001).OnlythestudyofLoxetal.(95)reportedstrengthchangesfromaerobicexer-
cisealone,withadifferenceafterinterventionintheIGof0.9kg,withasmalleffectsizeof
0.02fortheupperbodystrengthand12.8kgwithamoderateeffectsizeof0.59forthelower
bodystrength.
Professionalsupervisionwasreportedforupperbodystrengthinsevenstudies.Onlythe
chestpressmusclegroupwasreportedinthesestudies,withasignificantchangeintheIGof
17.9kg(95%CI:10.5–25.3,p<0.001).
Eightstudiesreportedachangeinlowerbodystrengthunderprofessionalsupervisionin
theIGof19.5kg(95%CI:13.4–25.7,p<0.001),whichwashigherthanthemainmeta-analy-
sis.SeeTable3.
Afterexcludingstudiespre-ARTera,performedorpublishedbeforeorintheyear1996
[75],asignificantchangeintheIG’supperbodystrength(19.9kg[95%CI:12.3–27.5],
p<0.001)andlowerbodystrength(15.1kg[95%CI:11.4–18.8],p<0.001)wasfound,where
theresultforIGupperbodystrengthwashigherthanthatofthemainmeta-analysis.
AnalysisofIGbodystrength,afterexcludingstudiesusingactivecontrolgroups,founda
significantchangeforupperbodystrength(24.3kg[95%CI:12–36.7],p<0.001)andlower
bodystrength(12.8kg[95%CI:8.8–16.8],p<0.001),althoughtheresultsfromthemain
meta-analyseswerehigherforlowerbodystrength.Upperandlowerbodystrengthheteroge-
neitywashigh(>75%)forthetwomainmeta-analysesandallsub-analyses.SeeTable3.
PLOSONE|https://doi.org/10.1371/journal.pone.0203384 September4,2018 9/21
EffectsofexerciseonPLWHstrengthandhormones:Ameta-analysis
Table3. BodystrengthchangesfrombaselineinPLWH.
Category ntrials(nparticipants) Change(kg) Overalleffect Heterogeneity
WMD 95%CI Z(p) I2
Upperbodystrength
Chestpress 10(284) 21.5 13.7–29.2 5.4(<0.00001) 98%
Bicepscurl 4(90) 6.7 -0.6–13.9 1.8(0.07) 95%
Long-termexercise
Chestpress 3(86) 16.4 4.8–28.1 2.8(0.0006) 95%
Bicepscurl 2(68) 9.9 3.1–16.7 2.9(0.004) 91%
High-qualitystudies
Chestpress 6(162) 24.2 11.9–36.5 3.8(<0.0001) 98%
AERT
Chestpress 5(160) 25.9 16.8–35.1 5.5(<0.00001) 96%
Bicepscurl 2(70) 3.4 -2.8–9.5 1.1(0.29) 90%
RT
Chestpress 4(102) 18.9 17.2–20.7 21(<0.00001) 99%
Professionalsupervision
Chestpress 7(190) 17.9 10.5–25.3 4.8(<0.00001) 96%
Post-ARTera
Chestpress 8(238) 25 16.3–33.7 5.6(<0.00001) 98%
Bicepscurl 4(90) 6.7 -0.6–13.9 1.8(0.07) 95%
Onlypassivecontrols
Chestpress 4(145) 28.8 15.8–41.9 4.3(<0.00001) 98%
Lowerbodystrength
Legpress 7(192) 31.7 21.1–42.3 5.9(<0.00001) 97%
Legflexion 9(289) 9.9 5.5–14.2 4.5(<0.00001) 95%
Legextension 8(255) 14.9 6.1–23.7 3.3(0.0002) 93%
Long-termexercise
Legpress 2(69) 46.1 -27.7–119.9 1.2(0.22) 92%
Legflexion 3(89) 10.3 5.5–15 4.2(<0.0001) 83%
Legextension 3(89) 20.9 16.7–25 9.9(<0.00001) 19%
High-qualitystudies
Legpress 4(101) 41.1 19.1–63.1 3.6(0.0003) 98%
Legflexion 6(191) 13.5 7.4–19.7 4.3(<0.0001) 96%
Legextension 5(157) 18.7 6.3–31.2 2.9(0.003) 94%
AERT
Legpress 3(96) 11.6 5.4–17.8 3.7(0.0002) 87%
Legflexion 6(216) 6.2 1.7–10.7 2.7(0.007) 93%
Legextension 7(235) 14.4 4.2–24.5 2.8(<0.00001) 93%
RT
Legpress 3(75) 47 25.2–68.9 4.2(<0.0001) 95%
Legflexion 3(73) 16.7 4.4–29 2.7(0.008) 96%
Professionalsupervision
Legpress 4(93) 35.3 9–61.7 2.6(0.009) 98%
Legflexion 4(109) 8.5 4.5–12.4 4.2(<0.0001) 80%
Legextension 4(105) 18 7.5–28.6 3.3(<0.0008) 77%
Post-ARTera
Legpress 6(149) 29.9 18.5–41.4 5.1(<0.00001) 97%
Legflexion 9(289) 9.9 5.5–14.2 4.5(<0.00001) 95%
(Continued)
PLOSONE|https://doi.org/10.1371/journal.pone.0203384 September4,2018 10/21