w w 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
Original
article
HIV-infected
youths
transitioning
from
pediatric
to
adult
outpatient
care
in
a
teaching
tertiary
care
hospital
in
São
Paulo
city,
Brazil
Angela
Carvalho
Freitas
a,∗,
Vivian
Iida
Avelino-Silva
a,
Eliana
Battaggia
Gutierrez
b,
Heloisa
Helena
de
Souza
Marques
c,
Giuliana
Stravinskas
Durigon
c,
Aluisio
Cotrim
Segurado
aaUniversidadedeSãoPaulo,FaculdadedeMedicina,DepartamentodeMolestiasInfecciosaseParasitárias,SãoPaulo,SP,Brazil bServic¸odeAtendimentoEspecializadoemDSTeAIDS,SecretariadeSaúdedaPrefeituradoMunicípiodeSãoPaulo,SãoPaulo,SP,Brazil cUniversidadedeSãoPaulo,FaculdadedeMedicina,InstitutodaCrianc¸a,SãoPaulo,SP,Brazil
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Articlehistory:
Received11August2018 Accepted21July2019
Availableonline31August2019
Keywords: Adolescent Youngadult PediatricHIV Transition-to-care Adultcare
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s
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c
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Background:HIV-infectedchildrensurvivinguntiladulthoodhavebeentransitioningtoadult outpatienthealthcareserviceinBrazilsincethelate2000’s.Deteriorationofclinical con-ditionisexpectedduringthisperiod,asreportedamongyouthswithnon-communicable chronicdiseases.Despitetheiryoungage,theyarelong-termhostsofthevirus,have pro-longedexposuretoantiretroviraltherapyandhavesufferedfromthesocialdeterminants andstigmaofHIVinfectionsinceearlychildhood.
Objectives: Thisstudyaimedto(1)describedemographicandclinicalcharacteristicsatthe firstappointmentatadultcareservicefollowingpediatriccareofacohortofBrazilianyouths livingwithHIVsincechildhood;and(2)retrospectivelyaddressadherenceandclinical vari-ablesinthelasttwoyearsofpediatricfollow-up.
Methods:Descriptivestudy.
Results:41consecutivepatientsreferredtoadultoutpatientcarefromapediatricHIVunit wereenrolled,medianage19years,andmedianlifetimeCD4+nadir117cell/mm3;89%
reportedpreviousAIDS-definingconditions.Atfirstlaboratoryassessmentinadultcare, only46%hadundetectable(<400copies/ml)HIVviralloadandthemedianCD4+countwas 250cell/mm3.
Conclusion: YouthslivingwithHIVatthetransitionfrompediatrictoadultcarehadpoor treatmentadherence,lowlifetimeCD4+cellnadir,lowCD4cellcountanddetectableHIV viralload.Healthcareprovidersshouldcloselymonitortheseadolescentsinayouthfriendly environment,preparedforopencommunicationaboutallaspectsoftheirhealth.
©2019SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.Thisis anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).
∗ Correspondingauthor:RuaFerreiradeAraujo,789SEAP-HCFMUSP,SaoPaulo,SP,CEP:05428-002,Brazil.
E-mailaddress:angela.freitas@hc.fm.usp.br(A.C.Freitas). https://doi.org/10.1016/j.bjid.2019.07.004
1413-8670/©2019SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
HIV-infectedpatientswhoacquiredtheinfectionperinatally or inearly childhoodand survived toadultage havebeen transitioningtoadultcareinrecentyears.InBrazil,thefirst cohortswerereferredtoadultcareinthelate2000’s.1The
com-plexperiodoftransitiontoadultcareisoftenassociatedwith deteriorationofclinicalcondition,whichhasbeenreported amongyouthswithnon-communicablechronicdiseases,such astypeIdiabetes,cysticfibrosis,rheumatoidarthritis, con-genitalheartdiseases,sicklecellanemia,andchronicrenal disease.2Insufficientknowledgeabouttheirownhealth
con-ditions,difficultiesinself-caremanagement,andtreatment fatigue contribute to the hindering of disease control and increased morbidity and mortality during this transitional period.2
YouthslivingwithHIVshareseveralofthese characteris-ticsbut alsopresentparticularfeaturesindimensionsthat rangefromhost-pathogenbiologicinteractionstothesocial determinantsoftheepidemic.3Despitetheiryoungage,they
arelong-termhostsofthevirusandthereforehaveprolonged exposuretoantiretroviraltherapy(ART).Adherenceto ther-apyisoftenachallengeinthispopulation,leadingtoimpaired immunereconstitutionandhighoccurrenceofHIV-resistance mutations.3–7Comorbiditiessuchascardiovasculardiseases,8
metabolic conditions,9–12 and psychologicalor
neurocogni-tivedysfunctions13–15 are also frequentin this population.
Moreover,patientsfacethesocialstigmaofHIVinfectionand remarkablechallengestoleadtheirsexuallives,1inadditionto
familyorsocialadversities,renderingthisgroupparticularly vulnerabletounfavorableoutcomesinclinicalcare.3,16–18
Theinfluxofalargenumberofpatientswithsuchcomplex issuesintoadultHIVoutpatientcaremayyieldasignificant burdentothesespecializedhealthservices.Adeeper under-standingoftheclinicalcharacteristicsand specialneedsof thisgroupattransitiontoadultcarecouldimprovestrategic allocationofresourcesaimingatamoresuccessfuldisease control.
Inthisstudy,wedescribedemographicandclinical char-acteristicsofacohortof41Brazilianyouthsattransitionfrom pediatrictoadultoutpatientcare.
Allparticipantsunderwentasimilarclinicalmanagement protocol,followingguidelinesofHIVtreatmentforchildren andadolescentsissuedbytheBrazilianMinistryofHealth.19–21
These protocols have been sequentially adapted reflecting newscientificdiscoveries, incorporationofknowledge,and theincreasingavailabilityofARTdrugs.
Methods
Studydesignandpopulation
AllconsecutiveyouthslivingwithHIVsincechildhoodwho werereferredfrompediatrictoadultHIVoutpatientclinics atourinstitutionbetweenJanuary2001andDecember2012 wereenrolled.Since2009,allpatientstransferredfrom pedi-atriccarewereindividuallyreportedwithacompletemedical historyjointlyrevisedbythepediatricandadultHIVclinicians.
Patients transferredbetween2001and 2009were identified usingadministrativeregistriesfromadultandpediatricclinics toidentifythosewithappointmentsatbothfacilities.Patients who,despitereferral,didnothaveanactualappointmentat theadultoutpatientclinicwereexcludedfromtheanalysis.
Theadultoutpatient cliniccomprisesadult HIVcareas well as teaching services formedicalstudents and fellows in Infectious Diseases, psychology,and socialservice, with approximately3000patientsundercareatthetimethesedata werecollected.Participantswerereferredfromthepediatric HIVcliniclocatedinadifferentfacilityofthesameinstitution.
Studyvariables
Datawerecollectedfrompediatricandadultmedicalrecords, laboratories, and administrative systems. The researchers used standardizedforms to collect the following informa-tion from the records: age at first visit to the adult care service (years); sex; race (categorized as white vs. others); orphanhood; typeof caregiver;sourceof infection; school-ingyears;occupation(categorizedasnooccupation;student only;employed;studentandemployed);sexualhealthhistory (sexualactivitystatusandpreviousorcurrentpregnancies); resultsoflaboratorytests(CD4+countsandHIVviralload -VL)performedatthelastvisitandtwoyearsprevioustothe lastvisitatthepediatricfollow-upandatthefirstvisittothe adultoutpatientcareservice(HIVVLconsideredundetectable when<400copies/ml-1.6log10/mL);lifetimeCD4+Tcellnadir
(CD4+nadir);timeintervalfromCD4+nadirtothefirstvisitof the adultoutpatientcareservice[months]; treatment char-acteristics(timeunderART[inyears],currentARTregimen, number ofpreviousARTregimens [categorizedas≤4or>4 previousregimens],numberofdailydosesandnumberofpills [categorizedas<4or≥4pillsperday]inthecurrentART reg-imen);previousHIVgenotypicresistancetests;AIDS-defining conditionsaccordingtoCDCclassification22duringpediatric
follow-up;AIDS-associatedmorbidities,hospitalizations,and comorbiditiesduringthe24monthspriortoreferraltoadult care(recordedasreportedinmedicalchartsduringroutine care,aswellasaccordingtoprescribedmedicalandbehavioral interventions);treatmentadherence(assessedusing1. medi-calcharts;2.missedappointmentswithhealthcareprovider, and3.recordsofARTdispensationatpharmacy).Poor adher-encewasdefinedashavinganyofthefollowing:description ofinadequate/lowadherenceinmedicalrecords;≥25%missed medicalappointments;<85%dispensationsofARTregimens fromtheinstitutionalpharmacyattimelyschedule (dispen-sationscompatiblewithadequateARTuptakeandrestock).
Statisticalanalysis
Descriptive analysis was performed using frequencies and percentages,mediansandinterquartileranges(IQR)for cat-egoricalandnumericvariables,respectively.Incidencerates ofAIDS-associateddiseasesandhospitalizationswere calcu-lated,asincidencedensityper100person-years,forthe 24 monthspriortoadmissionintheadultcare.Boxplotswere usedtoexploreCD4+countsandHIVVLaccordingto
adher-Table1–Demographiccharacteristicsof41HIVinfected youthsattransitiontoadultoutpatientcareatateaching tertiarycarehospital,SaoPaulo,Brazil,2001–2012.
Variable n(%) Median(IQR)
Age–years 19(18–20)
Female 22(54)
White 30(73)
Education-schoolingyears 12(11–12)
MTCT 39(95) Orphan 21(51) Caregiver Familymember 35(85) Birthparent 17(48) Fosterparent 2(6) Grandparent/otherrelative 16(46) Institution 5(12) None 1(2) Occupation Student 11(27) Employee 10(24)
Studentandemployee 8(20)
None 12(29)
MTCT,Mother-to-childtransmission;IQR,interquartilerange.
ence toART. All analyseswere performed usingStata 14.2 (StataCorp.CollegeStation,TX:StataCorpLP).
Ethicalissues
Our Institutional Ethics Review Board approved this study (protocol336.267).Allpatientidentifierswerekept confiden-tial.
Results
Forty-oneyouths reachedadult care service between 2001 and2012,90%ofthemfrom2009to2012.Maindemographic characteristicsaredescribedinTable1.Atotalof39(95%) par-ticipantswereinfectedthroughmother-to-childtransmission (MTCT)and2(5%)throughbloodtransfusion,bothbeforethe ageoffiveduringleukemiatreatment;bothhadremissionof thehematologicdiseasereportedinmedicalchartsbeforeHIV wasdiagnosed.
ClinicalcharacteristicsaresummarizedinTable2.Ofnote, mostparticipantshadapreviouslyimpairedimmunestatus, asshownbyalowmedianlifetimeCD4+cellnadirandahigh proportionofpatientswithpediatricCDCclassification22B2or
worse;mediantimebetweenCD4cellnadirandthefirstvisit totheadultoutpatientclinicwas 25months.Inlaboratory testscollectedatthefirstvisitatadultoutpatientcare,only 46%hadundetectableHIVVL,medianCD4+countwas250 cell/mm3 (IQR94–460),and75%hadCD4+countsbelow500
cell/mm3.Amongthe25(54%)youthswithadetectableHIV
VL,medianHIVVLwas3.83log10copies/mL(IQR3.08–4.37).
AsshowninFig.1,thegroupwithpooradherencehadlower medianCD4+countandhigherHIVVLcomparedtothegroup withgood adherence.Metabolicconditions,dyslipidemiain particular, accounted for the most frequentcomorbidities. Onlyonepatientinthecohorthadabnormalcognitive-motor
Table2–Clinicalcharacteristicsof41HIVinfected youthsattransitiontoadultoutpatientcareinateaching tertiarycarehospital,SaoPaulo,Brazil,2001–2012.
Variable n(%) Median(IQR) CD4count(cell/mm3) 250(94–460)
HIVviralload(copies/mL) 2.74(1.59–3.92) Undetectable(<400copies/mL) 19(46) Detectable(≥400copies/mL) 21(51) Ignored 1(2) PaediatricCDCAIDS-classification A1 1(2) A2 3(7) A3 – B1 1(2) B2 6(15) B3 7(17) C1 – C2 2(5) C3 21(51)
LifetimeCD4nadir(cells/mm3) 117(30–237)
TimebetweenCD4nadirand enrolment(months)
25(9–69) AIDS-relateddiseasesatpediatric
transitionperiod Tuberculosis 5(12) Herpeszoster 3(7) Oralcandidiasis 3(7) Esophagealcandidiasis 2(5) CMVmeningoencephalitis 1(2) Hodgkinlymphoma 1(2) Herpeticparaparesis 1(2) Recurrentpneumonia 1(2) Hospitalization 9(22) Comorbidities Dyslipidemia 14(34) Lipodystrophy 7(17) Dilatedcardiomyopathy 3(7) Abnormalcognitive-motor development 1(2) Other 7(17)
IQR,interquartileranges;CDC,CentersforDiseaseControland Pre-vention;CMV,cytomegalovirus.
development,reportedaslearningdeficitandimpaired self-careinpediatricmedicalcharts.
Inthe24monthspriortotransferencetoadultcare,34% ofparticipantshadbeendiagnosedwithAIDS-defining condi-tionsand22%requiredhospitalization.Tuberculosiswasthe leading AIDS-associated disease,followed by herpeszoster and esophagealcandidiasis,withincidenceratesof6.1,3.7 and2.4per100person-years,respectively.
As described in Table 3, inadequate adherence was reportedin54%ofmedicalrecords;12youths(29%)missed ≥25%appointments,and24youths(59%)haddelayedART dis-pensationsfromtheinstitutionalpharmacy.Altogether,using thesedifferentassessments,pooradherencewas character-izedin73%oftransitioningyouths.
Allcohortparticipantshadlong-termARTexposure.Most (78%)hadreceivedARTregimenscontaininglessthanthree drugsearlyinthecourseoftheirtreatment.Inaddition,HIV genotypictestswereperformedfor29%oftheyouthsduring
6 1,500 1,000 500 0 5 4 3 2 HIV vir
al load - log10 (copies/ml)
CD4+ count (cell/mm3)
Good (n=11) Poor (n=29) Good (n=11) Poor (n=29)
Adherence at pediatric service Adherence at pediatric service
a
b
Fig.1–Boxplotsof(a)HIVviralload(log10copies/ml)and(b)CD4+cellcount(cells/mm3)measuredatthefirstvisittothe
adultoutpatientcareservice,accordingtoadherencestatusduringpediatriccareservice.
Table3–Antiretroviraltreatmentcharacteristicsof41 HIVinfectedyouthsattransitiontoadultoutpatientcare inateachingtertiarycarehospital,SaoPaulo,Brazil, 2001–2012.
Variable n(%) Median(IQR) TimeonART–years 15(12–17) CurrentARTregimen
None 2(5)
2NNRTI 2(5)
2NRTI+NNRTI 12(29) 2NRTI+PI 17(41)
Others 8(20)
Currenttreatmentdosing
q.d. 2(5)
b.i.d. 37(95)
Numberofpillsincurrent ARTregimen
6(5–8) NumberofpreviousART
regimens
4(3–6) ReceivedARTregimenwith
<3activedrugs
32(78) UnderwentHIVgenotypic
testatpediatric transitionperiod
12(29)
ARTregimenchangedueto drugresistance
10(83) Adherence
Pooradherencereported inmedicalcharts 22(54) ≥25%missedmedical appointments 12(29) <85%oftimelyART withdrawal 24(59) Anyindicationofpoor
adherencea
30(73)
IQR,interquartileranges;NRTI,nucleosideandnucleotidereverse transcriptaseinhibitors;NNRTI,non-nucleosidereverse transcrip-taseinhibitors;PI,proteaseinhibitors;ART,antiretroviraltherapy; q.d,oncedaily;b.i.d,twicedaily.
a Presenceofeitherinadequateadherenceinmedicalrecords,≥
25%missedmedicalappointmentsor<85%timelyantiretroviral dispensationsfromtheinstitutionalpharmacy.
thelast24monthsatpediatricservice,triggeringmodification inARTregimensfor83%ofthem.
Asanimportantpartofyouthhealth,59%of34 partici-pantsreportedbeingsexuallyactiveandfour(10%)ofthem
wereeitherpregnantorhadpartnersexpectingachildatthe momentoftransferencetoadultcareservice.
Discussion
Inthisstudy,wepresentdemographicandclinical character-isticsofacohortofyouthsinfectedwithHIVearlyinchildhood (MTCTorbloodtransfusion)atthetransitiontoadultHIVcare aswellasHIVVLandCD4+cellcount/mm3atfirstassessment
intheadultcareservice.HavingacquiredHIVatthe begin-ningoftheBrazilianHIVepidemic,thiscohortwasexposed totheevolvingnationalrecommendationsforHIVtreatment thatguaranteesfreeaccesstoARTthroughthepublichealth caresystem(SistemaUnicodeSaúde,SUS)since1992.19–21As
such,theywerefrequentlyexposedtoregimenscurrently con-sideredsuboptimal,todrugsthataremorelikelytoinduce metabolicadverse eventsor tomedicationsnotadaptedto children’staste.Moreover,HIVVLtestswerenotavailablefor clinicalmonitoringuntillateintheirfollow-up.19–21
Pooradherenceduringthelast24monthsatpediatriccare was frequent,as in other Brazilianand foreign cohorts of youngadultslivingwithHIVsincechildhood,18,23–28and
dis-cordantoftheSwedishsingle-centercohort,thatreportspoor adherencebyonly12%.27Thishighlightstheexpected
diffi-cultiesin theclinical managementofthis specialgroupof patients.
At their first laboratory tests performed in adult care, youthsoftenexhibiteduncontrolleddisease,asseenbylow CD4+cellcountsandahighproportion(54%)ofpatientswith detectableHIVVL,similarlytoreportsfromothercohortsof transitioningyouths.7,28–30
Dyslipidemia wasthe mostcommoncomorbidityinthis population.ItcouldbeattributedtometaboliceffectsofART and/ortotheinflammatorystatusseeninchronicAIDS,or, alternatively,itcouldbeassociatedwithalesshealthydietand poorexercisehabits,asshownpreviouslyforthispopulation whenstillatpediatriccare.31,32Aimingtoprevent
cardiovas-culardiseases,ourfindings highlight theneedtoprioritize ARTdrugswithabettermetabolicprofileprovidedthatthey areactivetoeachparticularpatient.Wheneverpossible,this shouldbecombinedwithcontinuouscounselingfor health-ierdietandexercise.Althoughlifestylemodificationscanbe challenging,nutritionalcounselingandpromotionofphysical activitiesbyskilledpersonnelcouldbeimportanttoolsinthe comprehensivecareofthispopulation.
ThehighfrequencyofARTmodificationsafterHIV geno-typing tests and high number of pills in the current ART regimensupportthehypothesisthattheseyouthshadabad ARTresistanceprofileattransitiontoadultcare,ashasbeen previouslyreported.3,4,6,7,30Inaddition,theypresentedpoor
immunereconstitutionascomparedtoparticipantsfromthe IPECcohort,33aBraziliancohortincludingadultsaged18and
overatthebeginning oftheirHIVtreatment.Ourcohortof youthshadlowermedianCD4+cellcountscomparedtothe subgroupinIPECcohortthatinitiatedtreatmentinthesame period(2009–2012),i.e.250cell/mm3(IQR94–460)versus310
cell/mm3(IQR108–551).Furthermore,weobservedhigher inci-denceoftuberculosis(6.10/100person-years)duringthetwo yearspriortotransferencetoadultcare,ascomparedto a cohort of 599 adultpatients followed atthe same institu-tion(1.47/100person-years).34Exceptforhigherincidenceof
tuberculosis,AIDS-associateddiseasesinourcohortare con-sistentwithfindingsfromtheperinatallyinfectedyouthsin theIMPAACTstudy,35inwhichthemostfrequentlyreported
morbidities were herpes zoster, oropharyngeal candidiasis, esophagealorpulmonarycandidiasis,andpneumonia. Inter-estingly,despitetheirlowCD4+cellcount,youthsinourcohort didnotpresentwithcerebraltoxoplasmosisorPneumocystis jirovecipneumonia,commonlyseeninadultswithimpaired immunityandleadingcausesofAIDS-associatedillnessinthe IPECcohort.33
Socialandhouseholdcharacteristicsmayadddifficultiesto thecareandwellbeingoftheseyouths.Halfofthemhadlost bothparents,12%wereraisedininstitutionsandotherswere raisedbygrandparents,whoareexpectedtodecreasetheir supportpossibilitiesastheyage.AsreportedbyAcree,26adult
healthcareprovidersshouldencourageaslowtransitionfrom asocialsupportnetworktoautonomousself-care,avoidingan abruptbreakinpracticalandemotionalassistance.
Medianattainededucation of12schoolingyears reflects that most youths complete middle school education, but onlyhalfofthemreachtechnicaloruniversity-levelcourses. Our patients had low participation in the workforce (44% employed) and a high proportion (30%) ofthe cohort was neitheremployed nor studying. Thiscould reflect the cur-renteconomiccrisisinBrazil,furthercomplicatedbyfrequent absenteeismrelatedtohealthcareappointments.
Most patients in our cohort were sexually active. Sex-ual activity could be achallenge forthese youths. Studies aboutpregnancyinHIV-infectedadolescentsandyoungadults haveshownthatperinatallyinfectedpregnantyouths have higherratesofunintendedpregnancies,36loweradherenceto
ART,36,37andlowerratesofHIVdisclosurewhencomparedto
youthsinfectedsexually.38Thus,onecouldsuggesttheadult
healthcareteamtobeparticularlykeentoimplementaneasy channeltotalkaboutsexualityandfamilyplanningwiththese youths.
Accurate evaluation of treatment adherence is a chal-lengeinclinicalaswellasresearchsettings.39Astrengthin
our study was the assessment ofadherence using a com-binedevaluationofmedicalcharts,ARTdispensationatthe institutionalpharmacy,and missedappointmentswiththe healthcareproviders.
Alimitedsamplesizeshould beconsideredasa poten-tialweaknessofourstudy,reflectingthatMTCTisarelatively
rareeventinoursetting,potentiallyduetotestingand treat-mentstrategiesofferedtopregnantwomenintheBrazilian Aidsprogramsince1996.Additionally,thesmallnumberor participantsinourstudyalsosuggeststhatfewHIV-infected childrenhavesurvivedoverthefirstyearsoftheHIVepidemic and reachedadultcare. Moreover,due tothe retrospective natureofthestudywefailedtocollectinformationon sex-ual orientation, drug abuse, or psychosocial distress since suchinformationwas oftenlackingorincomplete in medi-calcharts.Finally,thefactthatourstudyaddressedpatients fromasingleinstitutionrestrictsgeneralizabilityofour find-ings.Nevertheless,ourstudydescribesoneofthefirstcohorts ofperinatallyinfectedyouthstransitioningtoadultcarein LatinAmerica,andhighlightspatientcharacteristicsthatare relevant toclinical managementin this population. Future multicenterstudieswithlargersamplesizeandlongitudinal follow-uparewarrantedtobetteridentifypredictorsofclinical outcomesinthisvulnerablepopulation.
In conclusion, most youths livingwith HIV since early childhood inour Braziliancohort reachedadultoutpatient careservicewithpooradherencetoART,lowCD4+cellcounts anddetectableHIVVL.AthirdofthemhadAids-associated illnesses inthelasttwoyearsofpediatricfollow-up.Based onourresultsaswell asonfindingsfrom othercohortsof youngadultslivingwithHIVsinceearlychildhood,we recom-mendthatadulthealthcareprovidersshouldcloselymonitor these transitioning youths. Comprehensive care should be offeredwithamulti-professionalteam,implementing proto-colstotracktreatmentfailure,stimulatehealthierlifestyles, encourageactiveparticipationofcaregiversinthetransition process,affordpsychologicalandsocialsupport,anddevelop ayouth-friendlyenvironmentpreparedforopen communica-tionaboutallaspectsofyouth’shealth.
Funding
Thisresearchdidnotreceiveanyspecificgrantfromfunding agenciesinthepublic,commercial,ornot-for-profitsectors.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgments
TheauthorskindlythankDelsaNagata,CamilaPiccone,Elza HabeandCleideMaluvayshifortheirvaluablehelpwithdata collection.
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