JPediatr(RioJ).2014;90(6):533---535
www.jped.com.br
EDITORIAL
Taking
care
of
the
caretakers
to
enhance
antiretroviral
adherence
in
HIV-infected
children
and
adolescents
夽
,
夽夽
Cuidando
dos
cuidadores
para
melhorar
a
adesão
antirretroviral
em
crianc
¸as
e
adolescentes
infectados
com
o
HIV
Yvonne
Bryson
DavidGeffenSchoolofMedicine,MattelChildren’sHospitalUCLA,DepartmentofPediatrics,DivisionofInfectiousDiseases, LosAngeles,UnitedStates
The article by Cruz etal., ‘‘Viral suppressionand adher-ence among HIV-infected children and adolescents on antiretroviraltherapy:resultsofamulticenterstudy,’’1
pub-lished in this journal reports important results regarding adherence to combined antiretroviral treatments from a large multicenter trial in perinatal human immunodefi-ciency virus (HIV)-infectedchildren and adolescents with HIV in five geographically-distinct reference centers of Brazil. Although major advances have been made in the diagnosis,treatment,andaccesstoantiviraldrugsfor chil-dren and adolescents withHIV, the desired outcome of a healthyand prolongedlife is limitedby theability of the child/adolescentandthecaregivertoconsistentlyadhereto thedailyneedtotakemultipleantiretroviralmedications.2
Chronicadministrationofmedicationisaconsiderable chal-lengeinmostpopulations,andespeciallysoinadolescents.3
DOIoforiginalarticle:
http://dx.doi.org/10.1016/j.jped.2014.04.007
夽 Pleasecitethisarticleas:BrysonY.Takingcareofthecaretakers toenhanceantiretroviraladherenceinHIV-infectedchildrenand adolescents.JPediatr(RioJ).2014;90:533---5.
夽夽SeepaperbyCruzetal.inpages563---71.
E-mail:ybryson@mednet.ucla.edu
As reported by Cruz et al., despite collection of data fromquestionnaireswithadherenceratesof92.6%of chil-dren(caregiversinformation)and77.2%ofadolescents,only 57%ofchildren and28/57 (49%)ofadolescentshad docu-mentedHIVRNAviralloadsbelow50cp/mL.Adherenceto medicationsis critical toassure persistent suppression of HIVtoundetectablelevels,whichallowsforthepotential reconstitutionofCD4T-cellsandimmunecompetence, pre-ventingtherapid developmentof antiviral resistanceand ultimate virological failure. There are limited opportuni-ties for new effective antiviral regimens, as observed in thispopulation,where63%of subjectswereonor beyond theirsecondregimen.Ourgoalsshouldbedirectedtowards improving medication adherence with the first regimen, giventochildrenandadolescentsasearlyaspossible follow-ingdiagnosisinordertomaximizethe long-termoutcome and reduce the potential for development of viral drug resistance.
Numerousstudieshaveuseddifferentmethodstoassess adherenceinHIV-infectedchildrenandadultswithvarying results.Inpediatricpopulations,adherencequestionnaires about cART-missed doses are used most frequently as in adults.Other methodsinclude recordsof pharmacyvisits; medication diaries; pill counts by study personnel and by electronic devices such as Medication Event Monitor-ing System (MEMS) (AARDEX Ltd, Union City, CA, USA)
http://dx.doi.org/10.1016/j.jped.2014.08.001
534 BrysonY
caps; and therapeutic drug monitoring.4---6 The article by
Cruz et al. found that the questionnaires about adher-encewereunreliable,sincethecaretakersandadolescent subjects were more optimistic about the consistency of adherencethanwhatwasevidenced bythepercentageof children/adolescentswithdocumentationofcontrolledviral replication.Severalkeypointsareworthyofreiteration;if instituted,theycouldimprovetheoveralloutcomeof HIV-infectedchildrenandadolescents.
The authors observed that careful monitoring of phar-macyrecordsarekeytoassureadherence,sincethosewho returnedapproximatelymonthlyfornewprescriptionswere significantlymorelikelytoremainvirologicallysuppressed thanthosewhocamelessfrequently. Thereoughttobea monthlyflagsenttocliniciansandcarepartnersif prescrip-tionsarenotpickedup.Otherinnovativesolutions,suchas homedeliveryof medications,couldbeusedifnecessary. Pharmacyreportscanprovideimmediatelyuseful informa-tionthatcanbeeasilyincorporatedintoroutinecareasa monitoringtool.7
Anotherkeycomponentwasthefindingthathealth;use of drugs and alcohol; and mental, cognitive, and quality of life assessments of the caregiver were very important inpredictingadherenceandinidentifyingareastoprovide assistance.TheauthorsusedtheAlcohol,Smoking,and Sub-stanceInvolvementScreening Test (ASSIST)asascreening toolforcaretakers;thispracticehasbeenproven success-fulinotherstudiesandisrecommendedbytheWorldHealth Organization(WHO)foradultswithHIV,sincemanagement ofsubstance abusehasbeen associatedwithcommitment tocARTtreatment28.
As expected, a negative association between moder-ate/heavy alcohol consumption and viral suppression has beenreportedin theliterature.8 Likewise,increased
anx-iety scores of caretakers have been associated withpoor adherence.Insuchcases,focusedinterventionstohelpthe caretakerscouldthenbeinstituted.Theincorporationofa screeninginstrumentfordruguseandqualityoflifeamong caregiversmaycontribute tostrategies aimingtoimprove adherenceinthepediatricpopulation.
Duringthisstudy,from2009to2011,themajorityof chil-drenandadolescentsinfollow-up werediagnosedlate,at a median of 9.5 years after the onset of symptoms, and 43%werediagnosedaftertheonsetofacquired immunode-ficiencysyndrome(AIDS),whichmayreflectontheabilityto achievesustainedviralsuppression,aswell asfamily atti-tudesaboutthenecessityofdailyARVtreatment.Thebest adherencerateswereobservedininfantsorchildren diag-nosedearly asa result of follow-up of a HIV-seropositive motherorfamilymember.
AdvancesintheintegratedcareofHIV-infectedpregnant mothersandHIV-exposedchildren,availabilityofearly diag-nosis,better accesstoantiviral medications,andchanges in ARV guidelines have greatly improved the initiation of cARVinpediatric andadolescent populationsinBraziland elsewhere.9
Duetoamajorreductioninearlymortalityand morbid-itywithinitiationofearlycombinedantiviraltreatmentin infants,treatmentofallHIV-infectedinfantsdiagnosedless thanoneyearisnowrecommended.10---12
ImprovingtheabilitytosustainHIVviralsuppressionisa continuingchallenge,notonlytoreducetheemergenceof
viraldrugresistanceandtoimprovethequalityoflife,but alsotoachievethepotentialfuturegoalofHIVremission.
Alargeclinicaltrialofpreventionofmother-to-childHIV transmissionconducted in Brazil,South Africa,Argentina, and the United States enrolled high risk infants within 48hoursofage,borntoHIV-infectedmotherswhodidnot receive prenatal treatment, andshowed thatinfants who receivedtwo or threeARVs prophylactically,comparedto singledose Zidovudine,had50% reductionoftransmission at the timeof birth.13 This study observed thatthe
iden-tification of HIV-positive pregnant mothers at thetime of deliveryandtheirhigh-riskHIV-exposedneonatesisfeasible inBrazilandinothermiddle-incomecountries,suchasSouth Africa;infantscanbestartedonARVveryearlyaspartof acomprehensiveprogramofpreventionofmother-to-child HIVtransmission.
The recent report of HIV remission in an infant who wasinfectedwithHIVinuteroandreceivedearly(31hours of age) triple combination treatment, who has been off antiretroviraltreatmentforthreeyearswithoutevidenceof HIVrebound,hasspurredfurtherstudiesofearlyARV treat-mentfor high-risk HIVinfants andisexpectedtoenroll in Brazil.14,15
In addition,recent studies in HIV-infected adolescents haveshown thatearlycombination treatmentat lessthan 6 monthsof ageand long-term, consistentlutightcontrol ofviralreplicationinperinatallyHIV-infectedpatientslead toreductionandcontinualdecayofHIVviralreservoirs.16---18
Improvedpoint-of-carerapiddiagnosisininfantsandmore frequentmonitoringofHIVviralloadinordertoassure ade-quateviralsuppressionarestillneeded.
Startingcombination ARV treatment early andassuring the best possible adherence during early years, with the goalofreducingHIVviralreservoirsandpreservingimmune function,and evenpreparingthese childrenfor strategies targetingHIVremission,iscriticalfortheirlong-term out-comeofthesechildren.
These new goals make the findings of the article by Cruzetal.evenmoreimportant,inordertodirectefforts to enhance adherence in this vulnerable population, who dependoncaretakersandmedicalinfrastructuretoensure that medications are available and delivered over many years.Weneedtohelptakecare ofthecaretakersofHIV infectedchildrenandadolescents.
Conflicts
of
interest
Theauthordeclaresnoconflictsofinterest.
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