JPediatr(RioJ).2015;91(6):509---511
www.jped.com.br
EDITORIAL
The
road
to
eliminate
mother-to-child
HIV
transmission
夽
,
夽夽
O
caminho
para
eliminac
¸ão
da
transmissão
vertical
do
HIV
Andrew
M.
Redmond
a,b,∗,
John
F.
McNamara
a,baInfectiousDiseasesUnit,RoyalBrisbaneandWomen’sHospital,MetroNorthHospitalandHealthService,Queensland,Australia bSchoolofMedicine,UniversityofQueensland,Queensland,Australia
TheWorldHealthOrganization’sGlobalHealthObservatory estimates that78 million peoplehave been infected with thehumanimmunodeficiencyvirus(HIV)duringthecourseof theepidemic,andthat39millionmen,women,andchildren havedied.1Nearly1in20adultsinsub-SaharanAfricaare
currentlylivingwiththeinfection.HIVrepresentsoneofthe world’smostserioushealthproblems.
The WHOglobalhealthsectorstrategyonHIV/acquired immunodeficiency syndrome (AIDS) has identified four strategic directions to guide countries’ HIV response to achievetheUnitedNations’MillenniumDevelopmentGoal ofhaltingthespreadofHIV/AIDS.Acoreelementof strate-gicdirectiononewastheeliminationofnewHIVinfections inchildren.2
It is encouraging that the number of new HIV infec-tionsin children isdecreasing inmost partsofthe world. In2011,therewereapproximately330,000newchildhood infections,andwhilethisisareductionof43%since2003, it remains unacceptably high.3 Unfortunately, increased
childhoodinfectionrateswereobservedinAngola,Congo, EquatorialGuinea,andGuinea-Bissau.
While a smallproportionof childhoodinfections result frombloodtransfusions, sexualabuse,orunsafeinjecting practices, the main cause is mother-to-child transmission
夽 Pleasecitethisarticleas:RedmondAM,McNamaraJF.Theroad
to eliminatemother-to-childHIVtransmission. JPediatr (RioJ). 2015;91:509---11.
夽夽SeepaperbydaRosaetal.inpages523---8.
∗Correspondingauthor.
E-mail:meinmuk@gmail.com(A.M.Redmond).
(MTCT),3,4 which may happen in-utero, peripartum, or
throughbreastfeeding.
SixteenmillionwomenwerelivingwithHIVattheendof 20135andmanyareofreproductiveage.Atotalof1,600,000
pregnancies arecomplicated by HIV infection worldwide, andMTCTrates,intheabsenceoftherapeuticintervention, areestimated to beas high as31%.6 Conditions resulting
inplacental inflammation, ageat first sexualintercourse, andgenitalulcerdiseaseareassociatedwithhigherratesof MTCT.
SubstantialimprovementsintheratesofMTCThavebeen achievedsincethefirstcaseofHIVMTCTwasidentifiedin 1983.RoutineHIVscreeninginpregnancyhasbeen recom-mendedsincethelate1990s;clinicaltrialsofantiretrovirals havedemonstratedsafe,efficaciousregimensduring preg-nancy,andfundshavebeendirectlyallocatedforresearch inMTCT.
Treatment of pregnant women with combination
antiretroviraltherapy(cART)hasleadtoadramaticimpact on MTCT.7 cART was shown to reduce MTCT by almost
20-fold.Itisestimatedthatbetween2009and2011,cART provided in pregnancy prevented 409,000 childhood HIV infections.3Inresponsetotheweightofevidencefor
pre-ventionofMTCT,theWHOConsolidatedGuidelinesonthe UseofAntiretroviralDrugsfor TreatingandPreventingHIV Infectionrecommends thatallpregnantandbreastfeeding women with HIV should be commenced on antiretroviral therapyandthosemeetingeligibilitycriteriashouldreceive lifelongtreatment.8
ItisbelievedthateliminationofMTCTcanbeachieved through effective antiretroviral coverage, education, and appropriate supportive care. However, antiretroviral
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510 RedmondAM,McNamaraJF
coverageof pregnantwomen withHIV remains poor, with only30%ofeligiblepregnantwomenreceivingantiretroviral therapy(ART),asopposedto54%foralleligibleadults.3The
majorityofHIV-infectedinfantsareborntomotherswhoare unawareoftheirHIVstatus,4highlightingtheimportanceof
screeningprogrammesduringpregnancy.
Asadevelopingcountry,Brazilbearsaheavyburdenof theHIVepidemic,andhasmadesignificantprogressin halt-ingthespreadoftheinfection.Brazilhasastableprevalence ofHIVestimatedat1%,withapproximately718,000people livingwiththevirus.TheprevalenceofHIVinfectioninkey populationsinBrazilisestimatedat5.9%amongdrugusers, 10.5%amongmenwhohavesexwithmen,and4.9%among femalecommercialsexworkers.9
In 2012, 8622 cases of AIDS were reported in women through the SINAN information system for notifiable dis-eases.Exposurein thesewomenwasdeterminedas96.6% heterosexual,2.5% intravenous drug use, 0.8% MTCT, and 0.1% via transfusion. In the ten years between 2003 and 2012,theageofpatientswithAIDShasshiftedtoyounger individuals, with highest rates observed in patients aged 30---49yearsofage.Therehasbeenan increasingtrendin detectionratesamongpeopleaged15---24years,9increasing
theproportionofwomenatreproductiveagewithHIV. TheBrazilian populationiswell-informedregardingthe transmissionofHIV:large-scalesurveysshowa97% agree-menttothestatementthatcondomuseisthebestwayto avoidHIV infection.Unfortunately,thisdoes nottranslate aswellaswouldbehopedtoaction,withonly55% preva-lenceofcondomusewithacasualpartnerintheprevious 12monthsinpeopleaged15---65years.9
Therehasbeenanoveralldecreaseinthedetectionrate ofAIDSamongstchildrenunder5years(35.8%)overtheten yearspreceding2012.Thisreductionwasnotobserved uni-formlyacrossBrazil,andincreasesinnotificationsofAIDSin childrenwereseenintheNorthandNortheastregions.9
MTCTremainsthemajorrouteofacquisitionof HIVfor children under 5 years of age in Brazil. Identification of HIVinpregnancyisimproving inBrazil,withanestimated screeningcoverageof80%inarecentstudyinwomen pre-sentingforpre-nataltesting.10However,itisestimatedthat
HIVtestingonlyreaches58.3%oftheexpectedcasesof HIV-positivepregnantwomen.9HIVinpregnancywasestimated
at0.38%prevalenceinBrazil,with50.7%ofthoseinfected withHIVagedbetween20and29years.
The article by da Rosa et al.,11 in this issue of Jornal
dePediatria,presentsaretrospectiveevaluationofratesof andfactorsassociatedwithMTCTofHIV-1atalarge hospi-talinSouthernBrazilovera14-yearperiod,between1998 and2011. Theauthorsextracteddatafromthelaboratory database and medical records for this purpose, and split thetimeintotwosectionsfor comparison.They reported that there had been a change in the prevalence of viral subtype C and in clinical management of HIV over time, althoughtheexact parametersofthesechangeswerenot presented.
During that period, there were 353 live births to HIV-infectedwomen.TherewasareductionintherateofMTCT ofHIVfrom11.8%to3.2%overthetwoperiods.The differ-encewashighlysignificant,bothstatisticallyandclinically, dramatically altering the lives of the children protected from HIV infection. The authors found that the rates of
low maternal viralload (<1000copies/mL), high maternal CD4+Tcellcount(>500
×109cells/mL),anduseofARTthat
wasdeemedcomplete(maternalARTduringpregnancyand at delivery and zidovudine post exposure prophylaxis for the neonate) increasedfrom the firstto the second time period. It was also observed that management of labour changedoverthetwoperiods,withmembranerupturetimes of greater than 4h being the norm in the earlier period (79.4%), butnot duringthe laterperiod(27%). Therewas not asignificant change in theroute of delivery over this time,howeveritislikelythatthechangeinmanagementof labourreflectsnationalhealthdepartmentpolicy.
The retrospective nature of the study prevents firm conclusions being drawn regarding the cause of the dra-matic fall in MTCT. Itis likelythat the fallin MTCT seen over the time evaluatedin this study is due toa combi-nationoffactors,butthatitisdominated bytheincrease intheproportionofwomenwithlowHIV viralload,which inturnisduetohigherratesofpregnantwomenreceiving cART.PreventionofMTCTisoneofthebenefitsoftreatment as prevention, and, as the implementation of this policy becomesmore widespread,both in Brazil andworldwide, wecanexpecttoseepreventionofdiseaseandprevention oftransmissionbothtochildrenofHIV-infectedmothersand tosexualpartnersofPLHIV.
A rangeof interventionsare recommended toprevent MTCTasoutlinedininternationalguidelines.12,13The
major-ity of these interventions are being applied in Brazil, with admirable timeliness, including identification of HIV infection in pregnant womenby screening during antena-tal care; engaging and retaining HIV-infected women in care; recommending andmaking available cARTfor these women;screeningforandtreatingothersexually transmissi-bleinfectionsinwomenatrisk;andprovidingpostexposure prophylaxisforchildrenofHIV-infectedmothers.9
Evidenceconcerningthe impactonMTCT of prolonged (>4h) rupture of membranes was evaluated in a meta-analysisin2001bytheInternationalPerinatalHIVGroup.14
This identified an increase in the risk of MTCT of 2% for each hour of membrane rupture. In contrast, a smaller, more recent study of 707 women who received prenatal careincludingARTatasinglecentreinMiami,Cotteretal. found no cases of perinatal transmission in women with plasmaviralloadsof<1000HIVcopies/mLwithmembrane rupture for up to 25h.15 In this cohort, only viral load
>10,000copies/mLwasanindependentriskfactorforMTCT. Sowhatisthedifferencehere?ItwouldappeartobecART. The studies included in the meta-analysis were predomi-nantlyconductedpriortotheavailabilityofcART,whilethe patientsintheMiami studywerereceivingcART.Whileda Rosa etal.11 found that prolonged rupture of membranes
wasariskfactorfortransmission,itislikelytobemuchless potentafactorthanuncontrolledHIVviraemia.Forwomen whohavenotachievedvirologicalsuppressionatthetime of delivery,it is likelythat elective caesareansection or, failingthat,avoidanceofprolongedruptureofmembranes isstillindicated.
Theroadtoeliminatemother-to-childHIVtransmission 511
such asthe engagementand retention in care of individ-ualswhouse injectable drugs,are morechallenging. Itis encouraging tosee the effortsand funding for this group beingprioritizedinBrazil.9WomenwhohaveHIVinfection
diagnosedduringpregnancyareakeyfocalgroup,asthere is less time between treatment initiation and delivery to achievevirologicalsuppressiontopreventMTCT.Also, treat-mentadherenceisakeyissueinHIVcarefor allpatients, but,asidentifiedinarecentreview,lessthanthreequarters of pregnant women have optimal treatment adherence.16
Whetherthisreflectsuncertaintyaboutthesafetyof medi-cationsforthefoetusorlackofengagementwithcare,this alsorepresentsakeyareaforattentiontoendHIV transmis-sion.
Thefindingsofthisstudy,alongwiththeresultsfromthe STARTstudyshowingtheclear individualhealth benefitof earlytreatment,17 tellusthatratherthancallingformore
research,itisnowtimetoimplementwhatwealreadyknow toachievethegoalofanHIV-freegeneration.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
References
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