w w w . e l s e v ie r . c o m / l o c a t e / b j i d
The
Brazilian
Journal
of
INFECTIOUS
DISEASES
Original
article
Osteopenia
and
osteoporosis
among
treatment-experienced
people
living
with
HIV
Bárbara
Marques
de
Castro
Lara
a,
Cristiane
Menezes
de
Pádua
b,
Cássia
Cristina
Pinto
Mendicino
b,
Gustavo
Machado
Rocha
a,∗aUniversidadeFederaldeSãoJoãodel-Rei,Divinópolis,MG,Brazil
bUniversidadeFederaldeMinasGerais,BeloHorizonte,MG,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received28January2020 Accepted28May2020 Availableonline15June2020
Keywords:
Antiretroviraltherapy Osteoporosis Osteopenia
Dual-EnergyX-Rayabsorptiometry screening
a
b
s
t
r
a
c
t
Introduction:Lifeexpectancyofpeoplelivingwithhumanimmunodeficiency(PLHIV)has
increasedmainlyduetotheaccessibilityandeffectivenessofantiretroviraltherapy(ART). However, adverse effects from long-term use of antiretrovirals, and the physiological changesassociatedwithaging,maycompromisethequalityoflifeofPLHIV,inaddition tocausingnewdemandsonthehealthcaresystem.
Objectives:Estimatethefrequencyofosteoporosisandosteopeniainpatientsonprolonged
ARTandtoverifytheirassociatedfactors.
Methods:Across-sectionalstudywasconductedinBeloHorizonte,MinasGerais,Brazil,from
August2017toJune2018,inasampleofPLHIV(age≥18years)whostartedARTbetween 2001and2005.Datawerecollectedthroughface-to-faceinterviews,physicalevaluation, laboratorytests,andDual-EnergyX-RayAbsorptiometryScreening(DEXA).Theoutcome ofinterestwaspresenceofbonealteration,definedaspresenceofosteopeniaor osteo-porosisinDEXA.Theassociationbetweentheexplanatoryvariablesandtheeventwas assessedthroughoddsratio(OR)estimate,with95%confidenceinterval(CI).Multiplelogistic regressionwasperformedtoevaluatefactorsindependentlyassociatedwithbonealteration.
Results:Among92participants,47.8%presentedbonealteration(19.6%osteoporosisand
28.2%osteopenia).Thevariablesthatremainedinthefinallogisticregressionmodelwere age≥50years(OR: 12.53;95%CI:4.37–35.90)andcurrentalcoholuse(OR:2.63;95%CI: 0.94–7.37).
Conclusions:Thisstudyshowedahighfrequencyofbonechanges,especiallyinPLHIVolder
than50years.Thisinformationisusefultostimulatethescreeningandtimely interven-tionofthiscomorbidityofPLHIVonprolongeduseofARTinordertopreventorminimize complicationsandnewdemandsonthehealthcaresystem.
©2020SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.Thisis anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).
∗ Correspondingauthor.
E-mail addresses: barbaramarquesdecastro@yahoo.com.br, barbara.fisio34@gmail.com (B.M. Lara), campadua@farmacia.ufmg.br
(C.M.Pádua),cassiamendicino@gmail.com,cassiamendicino@ufmg.br(C.C.Mendicino),gusrocha@ufsj.edu.br(G.M.Rocha).
https://doi.org/10.1016/j.bjid.2020.05.008
1413-8670/©2020SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Antiretroviraltherapy(ART)wasintroducedinthe1990sto controlhumanimmunodeficiency(HIV)replicationinpeople livingwithHIV(PLHIV).Asaresult,anincreaseinexpectancy and quality of lifeof PLHIV, and a significant decrease of HIV transmission in the general population were noticed. In addition, early initiation ofART contributes toimmune recoveryandpreventstheoccurrenceofacquired immunod-eficiencysyndrome(AIDS)cases.1 However,toachieve this
therapeuticsuccess,theindividualmustregularlytakeART whichisbasedonatleastthreedistinctantiretroviraldrugs. AccordingtotheBrazilianHIVguidelines,thefirstchoicefor treatmentshould includeacombination oftwonucleoside analogreversetranscriptaseinhibitors(lamivudineand teno-fovir)associatedwithanon-nucleosidereversetranscriptase inhibitor (efavirenz)or anintegrase inhibitor (dolutegravir; incorporatedfrom2017,becomingpreferredoverefavirenz).2
Between 2005 and 2015, there was a 45% reduction in HIV/AIDS mortalityworldwide,which reflectedanincrease inthenumberofPLHIV(from28millionto38.8million).In Brazil,thenumberofPLHIVincreasedfrom490,000in2005to 860,000in2017.Thisdropinmortalityrateswasmainlydue toasignificant increaseinthe proportionofPLHIVonART worldwide,from4.8%in2005to40.5%in2015.3,4 However,
prolongeduseofARTcombinedwiththenaturalagingprocess maycontributetotheoccurrenceofchronicdiseases.Among themaincomorbidities,metabolicalterationsshouldbe high-lightedsuchasdiabetesmellitus,dyslipidemia,liverdisease, nephropathy,andbonechangesincludingosteonecrosisofthe femoralhead,osteopenia,andosteoporosis.5,6
Osteopeniaandosteoporosisaremetabolicchangesthat leadtoreductionofbonemicroarchitecture,bonefragility,and increasedfracturerisk.7,8PLHIVpresenthigherfracturerisk
thanthegeneralpopulation.Inaddition,PLHIVmaypresent otherriskfactorsassociatedwithdevelopmentoffracturesin earlyages,suchaspresenceofmultiplecomorbidities, multi-pledruguse,peripheralneuropathy,andfrailty.9–11
DespitetheevidencethatprolongedARTuseleadstobone changes,this subjectispoorly investigatedinthe Brazilian context.Inanopen cohortstudy with 108PLHIV inBrazil, meanage43yearsandmeantimeonART5.2years,the preva-lenceoflowbonemineraldensity(BMD)was23.2%.12When
stratified byage, 54% ofpatients over50 years oldshowed decreasedBMDcomparedtoonly15%inyoungerpatients.In across-sectionalstudyin300patientswithsimilarmeanage andtimeonART,thegeneralprevalenceofdecreasedBMD was54.7%,withhigherprevalenceamongpeopleaged50or over(73.7%).13OtherstudiesintheUSfoundhighproportions
ofbonealterationinPLHIV,witha2–6%declineinBMD dur-ingthefirstyearsofARTuse,regardlessoftheantiretroviral regimen.14–17Thissignificantbonelossresemblesthe
popu-lationwithchronicglucocorticoiduse orthefirstyearafter menopause.18,19
Useof the antiretroviral tenofovir (TDF) has been more associated with increased bone loss when compared to other antiretroviral drugs.20 Prolonged TDF exposure
con-tributes to increased parathyroid hormone (PTH) activity, whichdecreasescalciumconcentrationinbonetissuewhile
increasingplasmaconcentration.21Actually,thereisevidence
thatbonelossoccurswithallARTregimens,possiblydueto increasedbonecatabolismafterviralsuppression.22–26
Despitetheknowledgeabouttheriskofbonealteration, furthercontextualizedstudiesareneededintheBrazilianHIV population,inordertoinvestigatetheimpactonboth qual-ityoflifeandthehealthcaresystem.Inaddition,guidelines areneededtoaddressscreeningandpreventiveactions.The currentknowledgeisnotsatisfactorilyappliedinclinical prac-tice,possiblyduetolackofawarenessandfinancialsupportin thisissue.Inthisperspective,thisstudyaimedtoestimatethe frequencyofosteopeniaandosteoporosisandtheirassociated factorsinasampleofPLHIVonprolongedARTuse.
Methods
Studydesignandpopulation
Thiswasacross-sectionalstudyconductedinthecityofBelo Horizonte,MinasGeraisstate,Brazil,fromAugust2017toJune 2018.Thisstudyincludedpatientsfromahistoricalcohortthat aimedtoevaluateadverseeffectsonprolonged ARTusein PLHIV(≥18years)whostartedARTbetween2001and2005 andcontinuedtoreceiveregularcareinapublicreferralcenter until2017/2018.27
Outcomeofinterestandexplanatoryvariables
The outcome of interest was presence of bone alteration (osteopenia or osteoporosis) diagnosed by the Dual-Energy X-RayAbsorptiometry(DEXA)methodandclassified accord-ingtoBMDlevel.BMDclassificationwasbasedontheWorld HealthOrganization(WHO)internationalstandards.For indi-viduals aged50 years and over, the T score was: a) DEXA T score> −1=absence ofbone alteration; b)DEXA Tscore between −2.5 and −1.0=osteopenia; and c) DEXA T score <−2.5=osteoporosis.Ontheotherhand,forindividualsunder 50yearsofage,DEXAZscore<of−2.0indicatesbonechange (withoutsub-classifications).7,8,28
Potentiallyexplanatoryvariablesweresociodemographic, clinical, lifestyle and dietary data, current use (yes or no) of alcohol, tobacco and illicit drugs, medication use, and healthcare system use. ART use was dichotomized by the mediantimeofuse.Thelevelofphysicalactivitywasassessed by Baecke’s questionnaire and categorized as insufficient (score<8.0)orsufficient(score≥8.0)levels.29Thisinstrument
evaluateshabitualphysicalactivity(atwork,atleisure,orin locomotionactivities)overtheprevious12monthsandhad beenvalidatedinBraziltothegeneralandHIVpopulation.30 Thereferencevaluesforbiochemicalexamswere:a)calcium: 8.5–9.5mg/dL;b)PTH:15–68.3pg/mL;c)vitaminD:>30ng/mL; d)phosphorus:2.5–4.5mg/dL;ande)creatinine:0.7–1.0mg/dL. HIVviralload(VL)wasclassifiedasdetectableorundetectable (<40copies/mL),andTCD4+lymphocytecountwas catego-rized using 500cells/mm3 as the cut-off value. Body mass
index(BMI)wascalculatedbyanthropometricdataregistered duringtheinterviews andclassifiedaccordingtoWHO rec-ommendations asnormal(18.5–24.9kg/m2), underweight(<
Recruitmentanddatacollection
Therecruitmentofeligiblepatientswasperformedin-person atthe public referral center, duringmedical appointments orARTdispensation.Patientswere invitedtoparticipatein the study and,incase ofagreement, tosign the Informed ConsentForm.Face-to-faceinterviewswereconductedusing asemi-structuredquestionnaire.Aftertheinterview,weight andheightweremeasuredusingaproperlycalibrated anthro-pometric scale. Biochemicalexaminations were performed intheclinicalpathologylaboratoryoftheFederalUniversity ofMinasGerais(UFMG)andbonedensitometry(DEXA)was assessedinaprivatelaboratory(GEHealthCare-LunarProdigy Advance-PA+130,267).Thetestresultswereattachedtothe participants’medicalrecordsandacopydeliveredtothemat thetimeofARTdispensation.Thedatawerecollectedthrough QuestionnaireDevelopmentSystemsoftware,version2.6.1.1.
Statisticalanalysis
Descriptiveanalyseswereperformedtocharacterizethestudy population. Thedifference between the proportions ofthe explanatory variables and outcome was assessed by Pear-son’s chi-squaretest inwhichvariables presentingp-value <0.25wereincludedintheinitialmultivariatemodel.Variables presentingp-value<0.05andthosewithepidemiological rele-vancewereconsideredforthefinallogisticregressionmodel. Themagnitudeofassociationswasestimatedusingoddsratio (OR),with95%confidenceinterval(CI).Statisticalanalysiswas performedusingEpiInfo® version7.2.2.6andSAS® software version9.2.
Ethicalconsiderations
This study was approvedby the ResearchEthics Commit-teeoftheFederalUniversityofMinasGerais(CAAENumber: 62710316.8.0000.5149)andbytheMunicipalHealthSecretariat of the city of Belo Horizonte. All participants signed the InformedConsentFormpriortobeginningdatacollection.
Results
Outofthe204individualsincludedinthecohortstudy,2745
(22.0%)didnotparticipateinthecurrentstudyduetodeath, treatmentabandonment,ortransfertootherhealthcare ser-vices,and 48 (23.5%)could not belocated. Amongthe 111 invitedpatients,17(15.3%)declinedtheinvitationand2(1.8%) haveturnedintheDEXAexam.Thus,92participantswereleft forthisanalysis.
Meanagewas52 years(56.5%>50yearsold),and most participantsweremale(56.5%),single,divorcedorwidowed (59.8%),non-white(78.3%),hadmorethaneightyearsof edu-cation(51.1%)andhad anincomelessthan orequaltoR$ 2,000.00(twothousandreais)(75.8%).Themajorityreported consumingmilk(77.2%)ordairyproducts(79.1%)and three or more cups of coffee daily (43.5%). Regarding drug use, 40.2%consumedalcohol,22.8%tobaccoand4.4%illicitdrugs (Table1).
Table1–Sociodemographic,clinicalandlaboratory profileoftreatment-experiencedPLHIV(N=92).
Characteristics N % Sex Male 52 56.5 Female 40 43.5 Age <50yearsold 40 43.5 50+yearsold 52 56.5 MaritalStatus
Single/divorced/widowed 55 59.8
Married/stableunion 37 40.2
Skincolor White 20 21.7 Non-white 72 78.3 Schooling 8+years 47 51.1 ≤8years 45 48.9 Monthlyincomea >R$2,000.00 22 24.2 ≤R$2,000.00 69 75.8 Milkconsumption Yes 71 77.2 No 21 22.8 Dairyconsumptiona Yes 72 79.1 No 19 20.9
Dailycoffeeconsumption
≤3cups 52 56.5
>3cups 40 43.5
Currentalcoholuse
No 55 59.8
Yes 37 40.2
Currenttobaccouse
No 71 77.2
Yes 21 21.8
Currentillicitdruguse
No 88 95.7
Yes 4 4.3
Physicalactivitylevel
Sufficient 35 38.0
Insufficient 57 62.0
Bodymassindex
High(overweight) 43 46.7
Normal 45 48.9
Low(underweight) 4 4.4
Previousbonefracture
No 56 60.9
Yes 36 39.1
Previousosteoporosisdiagnosis
No 91 98.9 Yes 1 1.1 Bonedensitometry Normal 48 52.2 Altered 44 47.8 Osteopenia 26 28.2 Osteoporosis 18 19.6 ARTtimea ≤15years 37 43.0 >15years 49 57.0 Viralloada Undetectable 72 80.0 Detectable 18 20.0 TCD4+lymphocytecounta Normal 68 77.3 Low 20 22.7
–Table1(Continued) Characteristics N % Creatininea Normal 70 77.8 High 20 22.2 Calcemiaa Normal 51 57.3 High 38 42.7 Phosphorusa Normal 82 93.2 High 6 6.8 VitaminDa Normal 22 47.8 Insufficient 24 52.2 Parathyroidhormonea Normal 34 55.7 High 27 44.3
Historyofkidneydisease
No 88 95.7
Yes 4 4.3
Historyofliverdisease
No 90 97.8 Yes 2 2.2 Historyoflipoatrophy No 62 67.4 Yes 30 32.6 VitaminDreplacement No 90 97.8 Yes 2 2.2
Currentuseoftenofovir
No 30 32.6
Yes 62 67.4
Currentuseofefavirenz
No 55 59.8
Yes 37 40.2
Currentuseofproteaseinhibitor
No 52 56.5
Yes 40 43.5
Currentuseofthiazidediuretics
No 81 88.0
Yes 11 12.0
Currentuseofglucocorticoids
No 89 96.7
Yes 3 3.3
a Excludedmissingdata.
Almost half of the participants were overweight, 4.4% underweight, and 62.0% had insufficient physical activity. TheminimumtimeofARTusewas12years,themaximum 17 yearsand the averagetime was 15years (57.0% of par-ticipants had been on ART>15 years). At the time of the interview,67.4% had been takingTDF, 40.2% efavirenz and 43.5%proteaseinhibitordrugs.Inaddition,12%hadbeen tak-ingthiazidediuretics,3.3%glucocorticoids,and2.2%vitamin Ddrugreplacement(Table1).
Outoftheparticipantswithavailabletests,44.3%presented highPTHplasmalevels, 52.2%insufficientvitaminD,42.7% highcalciumlevel,22.2%highcreatinine,and6.8%high phos-phoruslevels.MostparticipantshadundetectableVL(80.0%) andaTCD4+ lymphocytecountgreaterthan 500cells/mm3
(77.3%).Concerningclinicaldiagnoses,4.3%reportedkidney and2.1%liverdiseases;andin32.6%ofthepatients,
lipoatro-phywasdiagnosedornoticedbythepatientinsomepartof thebody(Table1).
Forty-four (47.8%) participants presented the outcome (28.2%osteopeniaand19.6%osteoporosisinDEXA),36(39.1%) reportedaprevioushistoryoffracture.Onlyoneparticipant hadbeendiagnosedwithosteoporosis(Table1).MeanBMDof thefemoralneckwas0.9363g/cm2(standarddeviation[SD]:
0.1659),and1.1345g/cm2(SD:0.1838)inthelumbarspine
(L1-L4).ThemedianTscoreandZscoreswere-1.2(SD:1.22)and -0.3(SD:1.12)forthefemur,and-0.7(SD:1,49)and-0.3(SD: 1.43)forthelumbarspine,respectively(Table2).
Univariateanalysisshowedthat71.2%ofthoseolderthan 50 years presentedbone alteration, compared to 17.5% of younger individuals (OR: 11.63; 95% CI: 4.22–32.0; p-value <0.001).Atotalof57.1%ofparticipantswithnormalor under-weightBMI(OR:2.25;95%CI:0.97−5.20;p=0.056)and75.0% of those with altered vitamin D levels (OR: 5.25; 95% CI: 1.48−18.66;p=0.008)hadbonealteration(Table3).The vari-ablesage≥50years(OR:12.53;95%CI:4.37–35.90)andcurrent alcoholuse(OR:2.63;95%CI:0.94–7.37)remainedinthefinal multivariatemodel(Table4).
Discussion
Inthis study,thefrequencyofosteopeniaandosteoporosis was considerablyhigher thaninthe generalBrazilian pop-ulation(rangingfrom 4.4%–27.4%).32,33 However,theserates
maybecomparabletothoseoftheelderlypopulation(over 65yearsold)inBrazil,whichrangesfrom33.3–57.4%.34
Con-sideringotherstudiesintheHIVpopulation,theseresultsare similartothatfoundbyPintoNetoetal.,inwhich54.8%had bonealteration,andbyEscotaetal.,whoreported61% alter-ationinapopulationonARTuseforatleastfouryears.13,14
Althoughforsomeauthorstheprevalenceandfactors associ-atedwithosteoporosisintheBrazilianpopulationareunclear, resultsofthisstudyshowthatboneabnormalitiesare man-ifested earlier and more frequently in PLHIV on ART use comparedtothe generalpopulation. Thesefindings under-scoretheimportanceofaspecificapproachtothesechanges aimingatreducingfragilityfractures,complications,and gen-eratingnewdemandsforthehealthcaresystem.35
Thefrequencyofosteoporosisfoundinthepresentstudy (19.6%),withameanageof52years,washigherthanthe fre-quencyfoundbyMary-Krauseetal.(14.6%),withameanage of46years.20Inaddition,themeanlumbarspineandfemoral
neckBMDfoundinthepresentstudyareclosetotheresults foundinaBrazilianstudywithasampleofolderpeople.36This
evidencecorroboratesthehypothesisthatthereisanearlier incidenceandhigherprevalenceofbonediseaseamongPLHIV. As shown, a positive and significant association was observedbetweenolderageandbonealteration.Ageisamajor riskfactorfordecliningBMDinbothPLHIVandthegeneral population.However,itisobservedthatthisdeclineaffects PLHIVonARTearlierthanthegeneralpopulation.Kanisetal. reportedthattheprevalenceofosteoporosisinPLHIVunder50 yearsoldcorrespondstotheprevalenceinEuropeanmenover 75years.37TheEuropeanClinicalAIDSSocietyrecommends
screeningforbonealterationbyDEXAinPLHIVover50years inmen,postmenopausalwomen,andadultswithriskfactors
Table2–EvaluationofDEXAquantitativevariablesintreatment-experiencedPLHIV(N=92).
Bonesegment Mean(SD)density(g/cm2) Median(SD)Tscore Median(SD)Zscore
Femoralneck 0.9363(SD:0.1659) −1.2(SD:1.2173) −0.3(SD:1.1192)
Lumbarspine(L1-L4) 1.1345(SD:0.1838) −0.7(SD:1.4879) −0.3(SD:1.4268)
SD:StandardDeviation;g:grams;cm:centimeters. Interpretation.
50+yearsold.
Tscore≥-1.0:nosignificantbonealteration. Tscorebetween−1.0and−2.5:osteopenia. Tscore≤−2.5:osteoporosis.
<50yearsold.
Zscore≤−2.0:altered(withoutsubclassifications).
suchashistoryoffragilityfracture,glucocorticoidtreatment formorethanthreemonths,orhighriskoffalls.38,39 Given
theseresults,trackingbonealterationfollowingthese recom-mendationsseemstobethebestwaytoavoidfracturesand othercomplications.
Inunivariateanalysis,lowvitaminDlevelswereassociated with bonealteration, despite the large number of individ-uals with missing vitamin D results. Adequate absorption ofcalcium,animportantelementinboneremineralization, requiresenoughlevelsofvitaminDtostimulateits absorp-tion from the intestine. Other effects ofvitamin D action includeregulationofbonereabsorption,enhancingcalcium reabsorptioninthedistalrenaltubules,andrepressionofPTH transcriptionandsecretion.40,41 Asaresult,thebonehealth
guidelinesforPLHIVadviseconsideringinterventionwith bis-phosphonate drugs, inaddition tocalcium and vitamin D replacementin casesof priorfracture or DEXA showingT scorebelow−2.5inanysegment.39Ina48-weekrandomized
clinicaltrialwith165adultsonART,itwasobservedthat cal-ciumandvitaminDsupplementationcouldattenuatebone decline.42However,furtherstudiesareneededtoevaluatethe
preventiveeffectofcalciumandvitaminDsupplementation amongPLHIVonARTinBrazil.Thus,accordingtotheDEXA resultsshowninthisstudy,22(25%)participantswouldhave aneffectiveindicationfortreatment.
Theassociation betweenbonealteration and normalor lowBMIfoundinthisstudyseemstocorroboratetheresults ofother studies.Pinto Neto et al.found asimilar associa-tion,althoughwithgreatermagnitude(OR:5.7and12.0,for normalandlowBMI,respectively).13Mary-Krauseetal.
com-plementthisassociationbyrecommendingscreeningformen under60yearsofageandBMI<20kg/m2.20Ameta-analysis
with10studiestotaling1371HIVpositiveand1644negative adults(ageandsexadjusted)observedthatPLHIVpresented a mean weight of 5.1kg lower than HIV negative controls (p<0.001).43UnadjustedanalysesfoundsignificantlowerBMD
inallbonesegmentsinPLHIV(p<0.01).Afteradjustmentfor body weight, the association remained significant fortotal hipandfemoralneck.Multifactorialdeterminantsmaycause bonedeclineinPLHIV,someofwhicharereversible.However, agingaffectsdirectlythebonechangesandalsomuscle tis-sue, causingsarcopenia, whichwilldirectly influencebone tissuemaintenance.Recommendationsforlifestylechanges suchasweight-bearingmusclestrengtheningandnutritional monitoringshouldbeaccessibletothispopulation.
The multivariate analysis identified a positive indepen-dentassociationbetweencurrentalcoholconsumptionand bone alterations. These resultswere corroborated by other studies.Tianetal.reportedalmost two-foldgreaterchance of bone alteration in postmenopausal women and elderly menwithalcoholhabits.44Inaddition,resultsfroma
meta-analysisalsoidentifiedalcoholconsumptionasriskfactorfor bonemineraldecline.45Apopulation-basedstudyconducted
in Norway found higher risk of hip fracture in individu-als with insufficient physical activity, history of smoking, and excessive alcohol consumption.46 Thus, greater
atten-tion,guidanceandscreeningshouldbeofferedespeciallyto PLHIV onARTpresentingother riskfactorssuchasalcohol use.
PLHIV mortality rates decreased substantially after the introduction ofhighly effectivecombined ART, resultingin aging of this population, which is increasingly affected by age-relatednon-communicableconditions.47Severalstudies
indicateahigherprevalenceandearlierincidenceofchronic diseases in PLHIV, compared to age-matched seronegative individuals, regardless ofsex.48,49 In this study, as already
mentioned,despitethehighfrequencyofbonealteration,only oneparticipantreportedpreviousosteoporosisdiagnosis.This resultisworrisome,showinglackoftrackingandawareness concerningtheproblem,whichcanbepreventablethrough lifestylechanges.
InthisstudynoassociationwasfoundbetweenuseofTDF and efavirenzwiththepresenceofbonechanges,probably due tothesamplesizeand designlimitations,whichhave neitherallowedtheestimationoftimeondrugexposurenor toestablishalogicaltemporalexposure.However,the litera-tureshowsapositiveassociation.Apublishedmeta-analysis found that although the proportion of individuals treated withproteaseinhibitorsorTDFwithosteopeniaor osteoporo-siswashigherwhencomparedtotheirrespectivecontrols, althoughtheseresultsdidnotreachstatisticalsignificance.45
Thus,itisstillunclearhowandwhichdrugsaretruly associ-atedwithdecliningBMD,requiringmorespecific,longer,and morerobustadditionalstudiestoconcludeandrefinefuture screening and management approaches and recommenda-tions.
Thisstudyhadsomelimitations,especiallyrelatedtothe samplesizeandthelackofcompleteinformationregarding laboratoryresults,reducingthestudypower.Forthisreason, somevariableswereanalyzedinadichotomouswayand it
Table3–Factorsassociatedwithbonealterationintreatment-experiencedPLHIV,UnivariateAnalysis(N=92).
Variables TotalN BoneAlteration(%) OR(95%CI) p-Value
Sex Male 52 55.7 1 Female 40 37.5 0.48(0.20−1.10) 0.082 Age <50yearsold 40 17.5 1 50+yearsold 52 71.2 11.63(4.22−32.0) <0.001 MaritalStatus
Single/divorced/widowed 55 49.1 1
Married/stableunion 37 46.0 0.88(0.38−2.03) 0.767
Skincolor White 20 35.0 1 Non-white 72 51.4 1.96(0.70−5.49) 0.194 Schooling 8+years 47 44.7 1 ≤8years 45 51.1 1.29(0.57−2.94) 0.537 Monthlyincomea >R$2,000.00 22 31.8 1 ≤R$2,000.00 69 53.6 2.48(0.90−6.83) 0.074 Milkconsumption Yes 71 45.1 1 No 21 57.1 1.63(0.61−4.34) 0.331 Dairyconsumptiona Yes 72 47.2 1 No 19 47.4 1.01(0.37−2.77) 0.991
Dailycoffeeconsumption
≤3cups 52 53.9 1
>3cups 40 40.0 0.57(0.25−1.32) 0.188
Currentalcoholuse
No 55 40.0 1
Yes 37 59.5 2.20(0.94−5.15) 0.067
Currenttobaccouse
No 71 43.7 1
Yes 21 61.9 2.10(0.77−5.69) 0.142
Physicalactivitylevel
Sufficient 35 42.9 1
Insufficient 57 50.9 1.38(0.69−3.95) 0.454
Bodymassindex
High(overweight) 43 37.2 1 Normal/Low 49 57.1 2.25(0.97−5.20) 0.056 ARTtimea ≤15years 37 46.0 1 >15years 49 51.0 1.23(0.52−2.88) 0.641 Viralloada Undetectable 72 47.2 1 Detectable 18 50.0 1.12(0.40−3.14) 0.832 TCD4+Lymphocytecounta Normal 68 47.1 1 Low 20 55.0 1.38(0.51−3.74) 0.532 Creatininea Normal 70 41.4 1 High 20 65.0 2.63(0.93−7.39) 0.062 Calcemiaa Normal 51 43.1 1 High 38 52.6 1.46(0.63−3.41) 0.374 Phosphorusa Normal 82 43.9 1 High 6 66.7 2.56(0.44−14.74) 0.279 VitaminDa Normal 22 36.4 1 Insufficient 24 75.0 5.25(1.48−18.66) 0.008 Parathyroidhormonea Normal 34 58.8 1 High 27 40.7 0.48(0.17−1.34) 0.160
–Table3(Continued)
Variables TotalN BoneAlteration(%) OR(95%CI) p-Value
Historyoflipoatrophy
No 62 46.8 1
Yes 30 50.0 1.14(0.47−2.72) 0.771
Currentuseoftenofovir
No 30 60.0 1
Yes 62 41.9 0.48(0.20−1.17) 0.104
Currentuseofefavirenz
No 55 45.5 1
Yes 37 51.4 1.27(0.55−2.92) 0.578
Currentuseofproteaseinhibitor
No 52 46.2 1
Yes 40 50.0 1.17(0.51−2.66) 0.714
Currentuseofthiazidediuretics
No 81 46.9 1
Yes 11 54.6 1.36(0.38−4.81) 0.634
a Excludedmissingdata.
Table4–Finallogisticregressionmodeloffactors associatedwithbonealterationamong
treatment-experiencedPLHIV(N=92).
Variables AdjustedOR(95%CI) p-Value
Age(50+yearsold) 12.53(4.37–35.90) <0.001 Currentalcoholuse(yes) 2.63(0.94–7.37) 0.066
wasnot possibletomakestratified analysisbysex orage. Theinformationwasobtainedfromasampleof92patients followed-upinasinglereferralservice,whichmightnot rep-resentthepopulationofPLHIVonlong-termARTuseinthe municipality.Thus,furtherstudieswithalargersampleand differentconditionsare neededtobetterevaluatethe mag-nitude and factors associated with bone alteration in this population.However,despitetheselimitations,itwas possi-bletonoticeahighfrequencyofbonealteration–osteoporosis andosteopenia–inthissampleofPLHIVlongtimeexposed to antiretroviral drugs, which reinforcesthe recommenda-tion for routinebone alteration screeningby densitometry intheSUS, aswell aspreventivemeasures,andwhen nec-essary, pharmacological treatment, in order to prevent or minimizecomplicationsandnewdemandsforhealthcare ser-vices.
Financing
source
This work received financial support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico -CNPq(ProcessNo.474547-2013-2),fromtheCoordenac¸ãode Aperfeic¸oamentodePessoaldeNívelSuperior–CAPES (post-graduatescholarship),andfromtheFundac¸ãodeAmparoà PesquisadoEstadodeMinasGerais–FAPEMIG(postgraduate scholarship).
Declarations
of
interest
Theauthorsdeclarenoconflictsofinterest.
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