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HIVinPregnancy
Author:TeresaMarino,MDChiefEditor:ThomasChihChengPeng,MDmore...
Updated:Jan15,2015

Overview
Thereductioninmothertochildtransmissionofhumanimmunodeficiencyvirus(HIV)isregardedasoneofthe
mosteffectivepublichealthinitiativesintheUnitedStates.Intheabsenceoftreatment,theriskofvertical
transmissionofHIVisashighas2530%.WiththeimplementationofHIVtesting,counseling,antiretroviral
medication,deliverybycesareansectionpriortoonsetoflabor,anddiscouragingbreastfeeding,themotherto
infanttransmissionhasdecreasedtolessthan2%intheUnitedStates.
Beforethecurrenttreatmentera,approximately2000babieswereinfectedwithHIVeachyearintheUnitedStates
alone.DespiteincreasingHIVprevalence,thatfigurenowstandsatapproximately300infantsperyear. [1]
Therapidclinicalimplementationofresearchfindingsdirectedtowarddecreasingperinataltransmissioniscredited
asthekeytothisaccomplishment.In1994,thePediatricAIDSClinicalTrialsGroup(PACTG)protocol076
demonstratedthattheadministrationofzidovudineduringpregnancyandlaborandthentothenewborndecreased
theriskofperinataltransmissionofHIVby68%,from25.5%to8.3%. [2]Inthelate1990s,thecombineduseof3or
moreantiretroviralmedicationswasfoundtobehighlysuccessfulatsuppressingviralreplication.
TheexactmechanismofmothertochildtransmissionofHIVremainsunknown.Transmissionmayoccurduring
intrauterinelife,delivery,orbreastfeeding.Thegreatestriskfactorforverticaltransmissionisthoughttobe
advancedmaternaldisease,likelyduetoahighmaternalHIVviralload. [3]Unfortunately,about30%ofpregnant
womenarenottestedforHIVduringpregnancy,andanother1520%receivenoorminimalprenatalcare,thereby
allowingforpotentialnewborntransmission. [4]

Epidemiology
UnitedStatesstatistics
Earlyintheacquiredimmunodeficiencysyndrome(AIDS)epidemic,womenwererarelydiagnosedwithHIVor
AIDS,butby2005,womenrepresented27%oftheestimated45,669newdiagnosisofHIV/AIDS,withthegreatest
riseamongyoungwomen. [5]About80%ofnewcasesinwomenintheUnitedStatesarecontractedthrough
heterosexualintercourse,20%bycontaminatedneedles,andmostoftheremainingcasesbymaternalchild
transmission.Testingofdonatedbloodhasessentiallyeliminatedbloodtransfusionsasasourceofinfection.
OfwomenwithAIDS,71%werediagnosedbetweentheagesof25and44,implyingthatmanyofthemmayhave
beeninfectedasadolescents.IntheUnitedStates,AfricanAmericanandHispanicwomenrepresent25%ofthe
femalepopulationbutaccountfor82%ofthetotalnumberofwomenwithAIDS.Furthermore,womenofcolor
accountfor80%ofnewlydiagnosedHIV/AIDScases. [6]

Internationalstatistics
TheJointUnitedNationsProgrammeonHIV/AIDS(UNAIDS)hasestimatedthat,in2008,approximately33.4
millionpeopleworldwide(1%oftheglobaladultpopulationaged1549y)wereinfectedwithHIV,adeclinefrom
2006(39.5millionreportedatthattime)67%ofallpeoplelivingwithHIVworldwideliveinsubSaharanAfrica,and
91%ofallnewinfectionsamongchildrenoccurthere. [7]
Morethan500,000babiesworldwidecontractHIVfromtheirmothers90%ofthesecasesoccurindeveloping
countries.In2005,AIDSclaimedanestimated2.43.3millionlivesmorethan500,000ofwhichwerechildren.One
thirdofthesedeathswereinsubSaharanAfrica. [5]

ProphylaxisandPregnancyOutcome
TheAntiretroviralPregnancyRegistry,wherecliniciansshouldreportcasesofexposuretoantiviraltherapyin
pregnancy,containsapproximately5,000reportedexposuresandnotesnoincreaseinthecongenitalmalformation
ratewithexposuretoantiretroviralmedications,eveninthefirsttrimester,withtheexceptionofefavirenz.Early
exposuretoefavirenzhasbeenassociatedwithneuraltubedefects.
Concernwasraisedthatantiretroviraltherapymayincreasetheincidenceofadversepregnancyoutcomes.Several
studieshaveshownthatzidovudinemonotherapyhadnonegativeeffectonpregnancy.
AlthoughdatafromcohortsintheUnitedStateshavenotshownanincreasedriskofpretermbirthwithcombination
therapy,aEuropeancollaborativestudyshowedanincreasedriskofpretermlaborinwomeninfectedwithHIVwho
weretakingcombinationantiretroviraltherapy,withanoddsratioforpretermbirthof1.8forcombinationtherapy
withoutaproteaseinhibitorand2.6forcombinationtherapythatincludedaproteaseinhibitor. [8]
InaUSstudyofpregnantwomeninfectedwithHIV,theoverallrateofadversepregnancyoutcome,including
prematurity,lowbirthweight,stillbirth,andabnormalApgarscores,wassimilarinwomenwhoreceivedantiretroviral
therapyduringpregnancyandthosewhodidnot. [9]Ofthe2123womeninthestudy,1590receivedmonotherapy,
396receivedcombinationtherapywithoutaproteaseinhibitor,and137receivedcombinationtherapywitha
proteaseinhibitor1143didnotreceiveantiretroviraltherapy.
Ratesofprematurityandextremeprematuritydidnotdiffersignificantlyaccordingtoantiretroviralregimen.
Althoughtheriskoflowandverylowbirthweightwasgreaterinthegroupreceivingaproteaseinhibitor,theresults

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didnotreachstatisticalsignificance.Furthermore,thismaybeareflectionofhigherviralloadoradvancedstageof
diseaseratherthanexposuretoproteaseinhibitors. [9]
Inamorerecentretrospectivestudy(20042012)thatevaluatedUSinfantgrowthpatternsduringtheirfirstyearof
lifeamongthoseborntoperinatallyHIVinfected(PHIV)(32infants,25mothers)andnonperinatallyHIVinfected
(NPHIV)mothers(120infants,99mothers)whoreceivedcare,infantsofPHIVmothershadlowermeanlengthfor
agezscores(LAZ)thatwereassociatedwithbirthlength.Othersmallforgestationalageanthropometricparameter
associationsincludedthoseofbirthweightandweightforagezscores(WAZ)andthoseofbothbirthlengthand
weightwithweightforlengthzscores(WLZ).TheinvestigatorsalsoreportedanassociationbetweendeliveryHIV
RNAlevelbelow400copies/mLwithincreasedWAZandWLZ. [10]
Alargemetaanalysisthatincludedarticlesfromseveralcountriesbetween1998and2006showedthatoverall,
highlyactiveantiretroviraltherapy(HAART)didnotincreasetheriskofprematurityhowever,theuseofregimens
withproteaseinhibitorsseemedtoincreaseprematurityslightly. [11]
ApossibleassociationexistsbetweenHAARTandpreeclampsia. [12]
ThedevelopmentofglucoseintolerancemaybemorecommoninpregnantwomenwithHIV.Originallythoughtto
beassociatedwithproteaseinhibitors,gestationaldiabetesappearstobesomewhatincreasedregardlessofthe
medicationregimen.Assuch,duringpregnancy,womenshouldbescreenedandmonitoredforglucoseintolerance.
[13]

HIVandPregnancyPlanning
PreliminarydatasuggestthatwomenwithHIVmaysufferfromsubfertility.Conceptionincoupleswhohavenever
conceivedmayoccurinamedianof6monthswith2actsofintercourseduringtheovulatoryperiodofthecycle.
Witheachact,theriskofsexualtransmissionmustbeconsideredeveninthepresenceofanundetectableviral
load.ConductingtestingandconsideringreproductivetechniquesinwomeninfectedwithHIVmaybeworthwhilein
anefforttoreducetheriskofinfectiontoahealthypartner.
Incouplesplanningapregnancywhereonlythemalepartnerisinfected,naturalconceptioncarriesariskofsexual
transmissiontotheuninfectedfemale.Counselingprovidedtosuchcouplesshouldincludestrategiestominimize
HIVtransmission.Optionsincludeadoption,spermdonation,andassistedreproductiontechniques.While
antiretroviraltherapycanreduceviralloadinthebloodtoundetectablelevels,somereportshaveshownthatmen
canstillhaveasubstantialviralconcentrationinsemeninthepresenceofanundetectableplasmaviralload.
Whenpossible,confirmationofundetectableseminalplasmaviralloadmaybeconsidered.IfHIVviralloadcannot
besuppressed,semenwashinghasbeenproposedandmaydecreasetheHIVRNAandDNAtoundetectable
levels.Afterprocessingandrecheckingforresidualcontamination,thespermatozoacanbeusedforintrauterine
inseminationorinvitrofertilization.
PregnancydoesnotappeartoinfluencetheprogressionofHIVdisease. [14,15]AlargecohortofFrenchwomenwith
knownseroconversiondatesnotedapregnancyadjustedrelativeriskofprogressionfromHIVtoAIDSof0.7. [16]
Furthermore,pregnancydoesnotseemtoaffectsurvivalofwomeninfectedwithHIV. [17]
Forserodiscordantcoupleswhowanttoconceive,theuseofantiretroviraltherapy(ART)isrecommendedforthe
HIVinfectedpartner,withthestrengthoftherecommendationdifferingbasedontheCD4cellcountoftheinfected
partner.Additionally,NIHguidelinesincludediscussionregardingpreexposureprophylaxis(PrEP)studiesin
heterosexualcouples.NewrecommendationsregardingpericonceptionadministrationofantiretroviralPrEPforHIV
uninfectedpartnersmayofferanadditionaltooltoreducetheriskofsexualtransmission.Theguidelinesinclude
informationoncounseling,laboratorytesting,andmonitoringofindividualsonPrEPandtheimportanceofreporting
uninfectedwomenwhobecomepregnantonPrEPtotheAntiretroviralPregnancyRegistry. [18,19,20]
HIVinfectionriskreductionstrategiesinconjunctionwithrelativelyinexpensivefertilityawarenessmethods(FAMs)
maybeusefulforcounselingHIVserodiscordantcoupleswhowanttoconceive. [21]Suchmethodsincludeuseof
accessibleandhighlysensitive,butpoorlyspecific,strategieslikethecalendarmethod,basalbodytemperature
measurements,andcervicovaginalmucussecretionfeatures.Urinaryluteinizinghormonetestinghashighspecificity
andcostwithlesssensensitivity.Timedcondomlesssexhaslowcostbutnecessitatesunderstandinghowto
preciselypredictthefertileperiodinamenstrualcycle. [21]

PatientEducation
Approximately30%ofwomenintheUnitedStatesarenottestedforHIVduringpregnancy.Reasonsfordeclining
shouldbeexploredandpatientscounseledappropriately.Testingstrategiesalsoincludereofferingscreeninginthe
thirdtrimestertowomenwhodeclinedfirsttrimesterscreeningorwhoareinhighriskgroups.TheCentersfor
DiseaseControlandPrevention(CDC)recommendsroutinethirdtrimesterscreeninginwomenwithhighrisk
behaviorsorwhoexhibitsignsorsymptomsofthedisease. [4]
ClinicianswhocareforwomenwithHIVneedtoprovidefamilyplanningservicesandcounselingregarding
optimizinghealthstatus.Thisincludesencouragingcompliancetomedicationregimens,cessationofsmoking,and
updatingimmunizations.
Stressingtheimportanceoftakingtheirmedicationregularlytodecreasethepossibilityofthedevelopmentof
antiretroviraldrugresistancemayencouragewomentocomplywiththerapy.Cigarettesmoking,concurrentuseof
drugs(cocaine,heroin),andunprotectedintercoursehavebeenassociatedwithincreasedriskofperinatal
transmission.
Itisencouragingtonotetherehasbeenasubstantialreductioninsubstanceuseinthepast2decades. [22]Ina
retrospectivestudyovera23yearperiod(19902012)thatevaluateddatafromtwoprospectivecohortstudies
(WomenandInfantsTransmissionStudy,SurveillanceMonitoringforAntiretroviralTherapyToxicitiesStudy),
investigatorsnotedadramaticdecreaseinsubstanceuseamong5451HIVinfectedpregnantwomen(1990:82%
2012:23%).Therewasasignificantdeclineinuseofeachsubstancebetween1990and2006,whenitreacheda
plateau,whichtheinvestigatorssuggestedmayhavebeencausedbyanepidemiologictransitionoftheHIV
epidemicamongUSwomen. [22]Substanceusewasinverselyassociatedwithreceivingantiretroviraltherapy.
Womenwithmultiplepregnancieswithsubstanceuseintheirpreviouspregnancywereathigherriskofsubstance

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useintheirnextpregnancy. [22]
Unfortunately,15%ofwomeninfectedwithHIVreceivenoorminimalprenatalcare,and20%donotinitiate
prenatalcareuntillateinthethirdtrimester.Womenwhoarenottreatedduringpregnancyshouldbetreatedwith
oneoftheappropriateintrapartumantiretroviraldrugregimens.
Evenintheabsenceofantepartumtreatment,intrapartumandearlyneonatalprophylaxiscanreducethemotherto
childtransmissionrisk.Womenshouldbeextensivelycounseledregardingtheabilitytodecreasetheriskof
perinataltransmissionwithhighlyactiveantiretroviraltherapy(HAART)prophylaxisortreatment.Inwomenwhoare
beingtreatedwithHAARTandplanningapregnancy,theteratogenicpotentialofcertainantiretroviralmedications
mustbereviewedandeffectivecontraceptiondiscussed.Thesemedicationsshouldbestoppedpriortoplanninga
pregnancy.

HistoryandPhysicalExamination
History
Inpregnancy,theinitialhistoryshouldassessthestatusofthepatientsHIVdisease(eg,CD4+Tcellcount,viral
load),theneedforbeginningoralteringantiretroviralmedication,andwaystoreduceperinataltransmission.A
carefulreviewofthemedicalandsurgicalhistory,gynecologichistory,highriskhabits,andpreviousobstetrichistory
shouldbedoneatthefirstprenatalvisit.

Physicalexamination
Duringpregnancy,acompletephysicalexaminationmustbeperformed.Knowledgeofthenormalphysiologic
changesofpregnancy,suchasanenlargedthyroidglandandasystolicmurmur,isimportanttodifferentiatefrom
diseaseprocess.HIVinfectioncanaffectessentiallyallbodysystems.

Screening
TheAmericanCongressofObstetricsandGynecology(ACOG)recommendsroutineHIVscreeningforwomenaged
1964yearsandtargetedscreeningforatriskwomenoutsideofthisagereference.Allpregnantwomenshould
havetheirHIVserostatusevaluatedwhentheyfirstpresentforprenatalcare.
WomenshouldhavetherighttorefusetestingafterbeinginformedthatHIVtestingwillbedrawnaspartoftheir
routineprenatalpanel.Thisoptoutapproachtoprenatalscreening,asadvocatedbytheInstituteofMedicine,is
associatedwithhighertestingratesamongpregnantwomen.However,severalstateshavelawsthatprohibitthis
approachandmandatethatpatientssignconsentformsfortesting,knownastheoptinapproach. [23]

ELISA
Themostcommonscreeningtestisanenzymelinkedimmunosorbentassay(ELISA),whichlooksforthepresence
ofantibodies.Ifthistestresultispositive,theELISAisrepeatedtoeliminatelaboratoryerrorpriortoproceedingto
aconfirmatorytestbyWesternblot.TheELISAhas98%sensitivity.Falsenegativeresultsmayoccurearlyinthe
disease,andfalsepositiveresultshavebeenreportedaftercertainvaccines.Repeattestingseveralmonthslater
usuallyconfirmsseronegativityinsuchcases.ApositivetestissentforWesternblot.

Westernblot
FortheWesternblot,specificviralproteinsareseparatedbyelectrophoresis,andreactionofantibodyto3proteins
mustoccurforthetesttobeconsideredpositive.Indeterminateresultsoccurwhen1or2oftheproteinsare
present.Inlowriskpopulations,indeterminateresultsusuallyreverttonegativeoverseveralmonths.Westernblot
hasafalsepositiverateof1in20,000.

Bloodcountsandviralload
ForpregnantwomeninfectedwithHIV,inadditiontothestandardprenatalassessment,continuedassessmentof
HIVstatusisimportant.Acompletebloodcounttoassessanemiaandwhitebloodcellcountaswellasrenaland
liverfunctiontestsshouldbeincluded.InitialevaluationincludesCD4+counts,whichhelpdeterminethedegreeof
immunodeficiency.
Viralload,determinedbyplasmaHIVRNAcopynumber(copies/mL)assessestheriskofdiseaseprogression.The
viralloadisimportantindecisionsregardingmaternaltreatmentanddeliverymanagementhowever,because
perinatalHIVtransmissioncanoccurevenatloworundetectableHIVRNAcopynumbers,theviralloadisnotused
inpregnancytodecidewhethertostartantiretroviralmedications.
Ifaviralloadisdetected,antiretroviraldrugresistancestudies(HIVgenotype)shouldbeperformedbeforestarting
therapyunlessthediagnosisismadelateinthepregnancy,inwhichcasestartingmedicationswhileawaitingresults
isrecommended.Ingeneral,pregnancyhasnotbeenassociatedwithariskofrapidprogressionofHIV. [17]
Withappropriatetherapy,theviralloadshoulddropby1logwithinthefirstmonthandbecomenondetectablewithin
6monthsafterinitiatingtreatment.Thehighertheviralload,thelongerthedecreasemaytakehowever,iftheviral
loadpersistsorincreasesat6months,treatmentfailuremustbeconsidered.

Lipidprofileandultrasound
Otherlaboratorystudiesshouldincludealipidprofile,whichisnotusuallyobtainedinpregnancy.Although
cholesterolnormallyincreasesinpregnancy,baselinevaluesarerequired,ascertainmedicationshavebeen
associatedwithincreasedtriglycerideandcholesterollevels.Evaluationofotherinfectiousdiseasestatesand
possibleopportunisticinfections,suchassyphilis,cytomegalovirus,andtoxoplasmosis,alsoneedstobedone.
Initialobstetricultrasonographyforviabilityanddatingisimportantfordeterminingtreatmentandplanningdelivery.
Potentialteratogenicityishighestduringthefirsttrimester,andsomepatientsmayconsiderdelayingtreatmentuntil
afterthefirst12weeksofpregnancy.Inwomenwhoareseverelyill,therisksandbenefitsofthisdelaymustbe
weighed.Atargetedultrasonographymaybewarranteddependingonmedicationexposure.

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Hepatitistesting
HepatitisBsurfaceantigenstatusisrecommendedforallpregnantwomen.InthecaseofacutehepatitisB
infection(HBV),theriskofverticaltransmissionalsovarieswithgestationalage,withan8090%riskof
transmissiontotheoffspringiftheinfectionoccursinthethirdtrimester. [23]WomenwhoarecoinfectedwithHIV
andchronichepatitisBmayrequiredifferentmanagementinpregnancy.
CoinfectionwithHIVandhepatitisCvirus(HCV)iscommonandmayrangefrom1754%. [24]Thediagnosisof
hepatitisCisconfirmedbyidentificationofthehepatitisCantibodyviaanELISAtest.FalsenegativeHCVtest
resultsmayoccuriftheCD4countisverylow.Morespecifictests,(eg,hepatitisCviralRNAdetectionby
polymerasechainreaction)areavailable.Highmaternalviraltitershavebeenassociatedwithanincreasedriskof
verticaltransmission.
AllwomenwhoarechroniccarriersofHBVorHCVshouldinformsexualpartners,householdcontacts,andneedle
sharingcontactsandreviewprecautionstodecreasetransmission.

Opportunisticinfectionassessment
AssessmentoftheneedforprophylaxisagainstPneumocystisjirovecipneumonia(PCP)orMycobacteriumavium
complex(MAC)infectionisnecessary.ForwomenwithlowCD4counts,prophylaxisforPCPiswithtrimethoprim
sulfamethoxazole(TMPSMX).Duetopotentialteratogenicity,aerosolizedpentamidinemaybesubstitutedinthe
firsttrimester,asitisnotabsorbedsystemically.ForprophylaxisofMAC,azithromycinisusedinplaceof
clarithromycinbecauseofpotentialteratogenicity. [14]

Othersexuallytransmitteddiseasetesting
Screeningforothermaternalsexuallytransmitteddiseasesisrecommendedinpregnancy.Forexample,screening
formaternalsyphilisisimportantnotonlyforthepreventionofcongenitalsyphilisbutalsobecausematernalsyphilis
hasbeenassociatedwithanincreasedriskofmothertochildtransmissionofHIV. [25]
Vaginalspeculumexaminationshouldbeperformedtoobtaincervicalcytologysmearandassaysforgonorrheaand
chlamydia.Allsexuallytransmitteddiseasesshouldbetreatedpromptly.Genitalwartsandvulvarintraepithelial
neoplasiaaremorecommonamongHIVseropositivethanHIVseronegativewomen,butwartregressionisas
commoninwomenwithHIVasthosewithoutandcancerisinfrequent. [26]WomeninfectedwithHIVhaveahigher
incidenceofcervicaldysplasia.

Vaccination
Vaccinationsshouldbekeptupdated.Duringpregnancy,liveattenuatedvaccines(eg,measlesmumpsrubella
[MMR],varicellavaccines)shouldbeavoided.Annualinfluenzavaccineandpneumococcalvaccineshouldbe
administeredtoallpregnantwomenwhoareHIVpositive.TheH1N1influenzavaccineshouldbeadministeredto
allpregnantwomenandissafeinwomenwithHIV.

Tuberculosistesting
CoinfectionwithHIVandtuberculosisisverycommonindevelopingnations.ImmunosuppressionfromHIV
infectioncontributesnotonlytoahigherrateoftuberculosisreactivationbutalsotoanincreaseddiseaseseverity.
Tuberculosisskintestingshouldbeperformedanda5mmpurifiedproteinderivative(PPD)resultinterpretedas
positive.Ifpositive,chestradiographycanbeperformedduringpregnancybecauseradiationriskisexceedinglylow.

Presentationduringlabor
Forwomenwhopresentinlaborandhavenothadprenataltesting,rapidtestingshouldbeoffered.Unlikethe
ELISA,therapidHIVtestisabloodorsalivaantibodytestandresultsareusuallyavailablewithinanhour.The
rapidtestisreportedtohaveahighnegativepredictivevalue(100%)andtobehighlysensitiveandspecific
(approaching100%)however,thepositivepredictivevalueinpregnancyvariesfrom44100%. [4]Patientswhotest
positiveinlaborbyELISAshouldbetreatedasHIVpositiveuntilconfirmatoryresultsareavailable.

AntiretroviralTherapy
Overview
Mothertochildtransmissionislinkedtoviralload.Assuch,antiretroviraltherapyshouldbeofferedtoallpregnant
womeninfectedwithHIVtoreducetheriskofperinataltransmissiontobelow2%. [27]Combinationantiretroviral
therapyshouldbeofferedinallcases.Aszidovudine(ZDV)istheonlyagentspecificallyshowntoreduceperinatal
transmission,itshouldbeusedwheneverpossibleaspartofthehighlyactiveantiretroviraltherapy(HAART)
regimen. [2]
Ifapregnantwomanhasreceivedantiretroviralmedicationinthepastbutisnotcurrentlyonanymedication,the
choiceofregimenmayvaryaccordingtothehistoryofprioruse,theindicationforstoppingtreatmentinthepast,
gestationalage,andresistancetesting.Inthissetting,ifthereisnoresistancetothedrugsandtheregimen
suppressedviralload,antiretroviralmedicationcanbeusedagain,butavoiddrugswithteratogenicpotentialor
adversematernaleffects.
IfapatientwhoisonaHAARTregimenpresentsforprenatalcare,continuinghertreatmentduringthefirst
trimesterisreasonable,providedthatcareistakentoavoidmedicationsthatarecontraindicatedinearlypregnancy.
HIVantiretroviraldrugresistancetestingisrecommendedifaviralloadisdetectable.Considerationsofdrugsnot
usuallyusedearlyinpregnancymaybenecessaryifdrugresistanceisconfirmedandthepatientreceivesextensive
counselingregardingriskandbenefits.
InanHIVinfectedpregnantwomanwhohasneverbeenexposedtoantiretroviralmedication,HAARTshouldbe
startedassoonaspossible,includingduringthefirsttrimester.Again,recommendationsarefordrugresistance
testingandcaretoavoidmedicationsthatmaypotentiallycauseadversematernalandfetaleffects.

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IfprenatalHIVtestingwasnotperformedandarapidHIVtestreturnspreliminarilypositive,thepatientshouldbe
treatedlikeanyotherwomaninfectedwithHIV.Certainly,thegestationalageandobstetricalscenariomaydictate
thetreatmentoptionsavailable,butastheexposurerisktoantiretroviralmedicationisminimaltobothmotherand
fetus,antiretroviraltherapyshouldbeinitiated. [4]
Thepatientwithapositiverapidtestmustbecounseledregardingthepossibilityofafalsepositivescreen,andthe
resultsshouldbedocumentedaspreliminaryinthemedicalchart.Ifthistestwasperformedonarrivalinlabor,
treatmentwiththeZDVprotocolthroughlaborisrecommended,followedbyadministrationtotheneonateuntil
confirmatorytestingonthemotherbecomesavailable.

Antiretroviralregimens
TreatmentofwomeninfectedwithHIVshouldnotbewithheldbecauseofpregnancy.Althoughthedecision
regardingstartingormaintainingcurrentantiretroviraltherapyisbasedonthesamecriteriaasinnonpregnant
patients,severalconsiderationsmustbetakenintoaccountbecauseofpotentialeffectsonthefetus.
Theuseofthe3partZDVprophylaxisregimen,aloneorincombinationwithotherantiretroviralmedications,should
bediscussedandofferedtoallpregnantwomenbecauseZDVwasthefirstagenttoshowsignificantdecreasein
themothertochildtransmissionofHIV. [2]Theregimenchosenshouldalsotakeintoaccountpriortherapyand
responsetothatregimen,aswellasresistancetesting.Gestationalageandpotentialfetalandneonataltoxicity
mustalsobetakenintoaccountwhenselectingaregimen.
Themechanismofactionwithwhichthesedrugsreduceperinataltransmissionincludesloweringmaternalviral
loadhowever,asthesedrugscrosstheplacenta,thereappearstobeprenatalprophylaxisaswell.Thethird
component,prophylaxisofthenewborn,furtherdecreasestheriskofperinataltransmission.
Theantiretroviraldrugsusedinpregnancyfallbroadlyinto3categories:thenucleosideandnucleotideanalogue
reversetranscriptaseinhibitors(NRTIs),nonnucleosidereversetranscriptaseinhibitors(NNRTIs),andprotease
inhibitors(PIs).Thereareinsufficientdatatoallowrecommendationsregardingtheuseofentryinhibitorsor
integraseinhibitorsinpregnancy.
GuidelinesforperinatalARTwererevisedinJuly2012regardingwhichagentsareconsideredpreferred,alternative,
ortobeusedunderspecialcircumstances.Combinationregimens,usuallyincluding2NRTIswitheitheranNNRTI
or1ormoreproteaseinhibitors(PIs)arerecommended.Forfurtherinformation,seeTable1.
Table1.ARTagentsduringpregnancy[18](OpenTableinanewwindow)
ARTClass

Preferred*

Alternate

SpecialCircumstances InsufficientDatatoRecommend

NRTIs

zidovudine(ZDV)

abacavir

didanosine

lamivudine(3TC)

emtricitabine stavudine

tenofovir

NNRTIs

nevirapine

efavirenz

etravirine

rilpivirine

PIs

atazanavir

darunavir

indinavir

fosamprenavir

lopinavir+
ritonavir

saquinavir

nelfinavir

tipranavir

enfuvirtide

ritonavir

FusionInhibitors

maraviroc

Integrase
Inhibitors

raltegravir

*ZDVplus3TCisarecommendeddualNRTIbackboneregimenplusanNNRTIand1ormorePIsforpregnant
womenwithHIV

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Nucleotideanaloguereversetranscriptaseinhibitors
TheNRTIsaregenerallywelltoleratedandcrosstheplacenta.TheFDAhasclassifiedtheseaspregnancyclassB
orC,dependingontheagent.ThesedrugsdobindtomitochondrialDNAgammapolymeraseandmaycause
mitochondrialdysfunctionmanifestingascardiomyopathy,neuropathy,lacticacidosis,andliverdysfunction.Genetic
susceptibilitytothesedrugsmayplayarole,andtheeffectsusuallyresolvewithcessationofthemedication. [1]
Thecombinationofdidanosineandstavudinehasbeenassociatedwithlacticacidosisandhepaticfailureleadingto
fatalitiesandshouldbeusedwithcautionoronlyincaseswhereotherNRTIscannotbeusedduetoresistanceor
toxicity.Finally,ZDVandstavudinehaveoverlappingtoxicitiesandareantagonisticandshouldbeavoidedin
combination. [27]
Nonnucleosidereversetranscriptaseinhibitors
FiveNNRTIsareFDAapproved:delavirdine(Rescriptor),efavirenz(Sustiva),etravirine(Intelence),nevirapine
(Viramune),andrilpivirine(Edurant).AlthoughlessinformationisavailableregardingNNRTIuseinpregnancy,
nevirapineandefavirenzbothcrosstheplacenta.Themostcommonsideeffectisrash,whichcanoccurinupto
17%ofpatientsonnevirapine. [14]
Useofefavirenzisnotrecommendedinthefirsttrimesterbecauseofreportedcasesoffetalneuraltubedefects.
TheFDAhaschangedthepregnancyclassificationofthisdrugtocategoryD. [28]
Severenevirapineassociatedskinrashandhepatictoxicityhavebeenreportedinpregnancy.Thepotentiallyfatal
hepatotoxicityappearstobeincreasedinwomen,duringpregnancy,andinpatientswithaCD4+Tcellcount
greaterthan250cells/mL.Becauseofthesesignificantcomplications,nevirapineshouldnotbeusedasfirstline
therapyunlessnootheroptionisavailable.
InwomenwhoseCD4+Tcellcountswerebelow200cells/mLandwhowerepreviouslyexposedtoperipartum
singledosenevirapine,ritonavirboostedlopinavirplustenofoviremtricitabinewassuperiortonevirapineplus
tenofoviremtricitabineforinitialantiretroviraltherapy. [29]
InchildrenpreviouslyexposedtosingledosenevirapineforperinatalpreventionofHIVtransmission,zidovudineand
lamivudineplusritonavirboostedlopinavirforantiretroviraltreatmentresultedinbetteroutcomesthantreatment
withzidovudineandlamivudineplusnevirapine. [30]
Proteaseinhibitors
Proteaseinhibitorsdonotcrosstheplacentaeasily,andnoteratogeniceffectshavebeennotedinanimals.They
areclassifiedasclassBorCbytheFDA.
AlsoseetheMedscapeDrugs&DiseasestopicAntiretroviralTherapyforHIVInfection.

PeripartumTreatment
InanypregnantwomaninfectedwithHIVwhopresentsinlabor,whetherherHIVpositivestatuswaspreviously
knownorwasdeterminedbyrapidtestresult,morethanonetreatmentoptionisavailableduringlaboranddelivery.
AllHIVinfectedwomenwithHIVRNA400copies/mL(orunknownHIVRNA)neardeliveryshouldbeadministered
IVzidovudine(ZDV)duringlabor,regardlessofantepartumregimenormodeofdelivery.IVZDVisnolonger
requiredforHIVinfectedwomenreceivingcombinationARTregimenswhohaveHIVRNA<400copies/mLnear
delivery. [18]
ZDVisgivenintravenouslyduringlaboratadoseof2mg/kginfusedover1hour,followedbyacontinuousinfusion
of1mg/kgthroughoutlabor.Thisregimen,alongwithmaternalantepartumandinfantzidovudine,reducedperinatal
transmissionby66%overall. [18]Ifthepatientishavingaplannedcesareandelivery,theIVinfusionshouldbegin3
hoursbeforetheprocedure. [14,27,31]AnotheroptionisZDVinfusionfollowedbyasingledoseof200mgof
nevirapine.Thisregimenshouldbefollowedbylamivudine(3TC)150mgevery12hours.Ifthelatterregimenis
usedinpregnancy,thepatientmustcontinueZDV/lamivudine(Combivir)foratleast7dayspostpartumtoavoid
nevirapineresistance. [14]
WomenwithdocumenteddrugresistancetoZDVorwhoseantepartumregimendidnotincludeZDVshouldstillbe
giventheintravenousZDVprotocolduringlaboranddeliveryorbeforecesareandelivery. [14,31]Furthermore,the
otherantiretroviralagentsmustbecontinuedonschedulethroughouttheintrapartumorpreoperativeperiod.
StavudineistheonlyagentthatcanantagonizeZDVandshouldbestoppedpriortotheIVinfusionofZDV. [27]
Inpatientsattemptingavaginaldelivery,allinvasiveproceduressuchasamniotomy,internalfetalscalpelectrode,
orscalpsamplingshouldbeavoided,asthesemayincreasetheriskoftransmission.
WhenHAARTisgivensolelyforpreventionofperinatalHIVtransmission,itmaybestoppedinthepostpartum
period.TheriskofpromotingthedevelopmentofresistantviralstrainsbyusingshortcoursesofHAARTcanbe
decreasedbyusingamaximallysuppressiveregimenanddiscontinuingallagentsatthesametime.Theexception
remainsiftheregimenincludesanucleosidereversetranscriptaseinhibitor(NRTI).TheNRTIshouldbecontinued
foranadditional7daystodecreasetheriskofresistance. [14]
InfantARTprophylaxis [18]
AllHIVexposedinfantsshouldreceivezidovudineinthefollowingdoses:
<30weeksgestation:2mg/kgPOor1.5mg/kgIVBIDafterage4weeks,advanceto3mg/kgPOor2.3
mg/kgIVq12hr
>30to<35weeksgestation:2mg/kgPOBIDafterage15days,advanceto3mg/kgPOor2.3mg/kgIV
q12hr
>35weeksgestation:4mg/kgPOor3mg/kgIVBIDx6weeks
Initiateassoonafterdeliveryaspossible(preferablywithin612hours)andcontinuethroughage6weeksand
administerbirththrough6weeks.
AdditionalprophylaxiswithnevirapineisneededforHIVexposedinfantsofwomenwhodidnotreceiveantepartum

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ARTatthefollowingweightsanddosages:
Birthweight1.52kg:8mg/dosePO
Birthweight>2kg:12mg/dosePO
Administer3dosesinthefirstweekoflife1stdose48hoursafterbirth,give2nddose48hoursafter1stdose,and
3rddose96hoursafter2nddose.

HepatitisCoinfection
ThecurrentrecommendationfortreatingwomencoinfectedwithHIVandHBVistotreatthesewomenwith
tenofovirandlamivudineoremtricitabine. [32]All3haveshownactivityagainstHBV.Ametaanalysisfoundthatthe
useoflamivudineeffectivelypreventsmothertochildtransmission,eveninpregnantwomenwhohaveahigh
degreeofHBVinfectiousnessinlatepregnancy. [33]
Althoughdataareinsufficientfortheuseoftenofovirinpregnancy,thebenefitslikelyoutweightherisksinwomen
withHBV/HIVcoinfection.Womenreceivingtreatmentshouldbeadvisedofthesignsandsymptomsofliver
toxicity,andregularfollowupoftransaminaselevelsiswarranted.TheinfantshouldreceivehepatitisB
immunoglobulinandstartthe3doseseriesofhepatitisBvaccinewithinthefirst12hoursoflife. [18]
PregnancydoesnotappeartoalterthecourseofHCVinfectionhowever,coinfectionwithHIVdoesappearto
increasetheriskofperinataltransmissionofHCV.Assuch,a3drugantiviralcombinationisrecommended
regardlessoftheviralload.AswithHBVcoinfection,patientsshouldbemadeawareofthesignsandsymptomsof
livertoxicity,andtransaminasesshouldbefollowedevery24weeks.
AswithHIV,prolongedruptureofmembranesmayincreasetheriskofperinatalHCVtransmissionhowever,the
dataremaininconclusiveregardingtheuseofcesareansectiondeliverytodecreasetheriskoftransmission.As
such,deliveryrecommendationsarebasedontheHIVstatus.InfantscanbeevaluatedbytestingHCVRNAat2
and6monthsofageorHCVantibodyafter15monthsofage. [18]

CesareanDelivery
Cesareandeliverymustbediscussedandthepatientcounseledregardingthepossibilityofanunnecessarysurgical
procedureshouldthefinalHIVresultbenegative. [18]Careshouldbeindividualizedaccordingtoclinicalscenario.
Earlystudiesregardingcesareandeliveryandtransmissionriskshowedconflictingresults.Cesareandeliverybefore
theonsetoflabormaypreventmicrotransfusionthatoccurswithuterinecontractions,andavoidingvaginaldelivery
eliminatesexposuretovirusinthecervicovaginalsecretionsandbloodattimeofdelivery.
Inthelate1990s,prospectivecohortstudiesnotedadecreaseinmothertochildtransmissioninwomenon
zidovudine(ZDV)whounderwentelectivecesareandeliverycomparedwithwomenwhodidnottakeZDV
prophylaxis. [34,35]In1999,resultsfromalargemetaanalysisofindividualpatientdatafrom15prospectivecohort
studiesdemonstrateda50%reductionofverticaltransmissionwiththeuseofelectivecesareandeliveryforwomen
withHIV,afteradjustingforantiretroviraltherapy,maternalstageofdisease,andinfantbirthweight.
Ofnote,verticaltransmissionriskdidnotchangewhenthestudygroupwaslimitedtothosewomenwhohad
ruptureofmembranesshortlybeforesurgery.Thetransmissionriskwasdecreasedbyabout80%forwomenwho
hadbothanelectivecesareandeliveryandweretakingantiretroviralmedication. [36]
Inthesameyear,ACOGissuedanopinionthatelectivecesareandeliveryshouldbediscussedandofferedtoall
pregnantwomenwhowereHIVpositiveat38weeksgestationtoavoidthepotentialriskofspontaneouslaborand
ruptureofmembranes. [31]
ThesestudiesdidnotadjustforviralloadandwereperformedbeforeHAARTcameintouse.InpatientsonHAART
withanundetectableviralload(<1000copies),theriskoftransmissionisverylow,andwhethercesareandelivery
offersanyfurtherbenefitremainsunknown.
ThisledtoanupdatedACOGstatementin2000,statingthatwomeninfectedwithHIVwhoseviralloadsare
greaterthan1,000copies/mLshouldbecounseledregardingthepotentialbenefitofscheduledcesareandeliveryto
furtherreducetheriskofverticaltransmissionofHIVbeyondthatachievedwithantiretroviraltherapyalone. [31]
However,dataareinsufficienttodemonstrateabenefitforneonatesofwomenwithviralloadslessthan1,000
copies/mL.
Longerdurationofrupturedmembranesmaybeassociatedwithahigherrateofmothertochildtransmission.The
InternationalPerinatalHIVgroupmetaanalysisfoundthattheriskofverticaltransmissionincreasedby2%for
everyincreaseof1hourinthedurationofrupturedmembranes.Ifcesareandeliveryisperformedaftertheonsetof
labororruptureofmembranes,thebenefitofsurgerymaybelost.Inthisscenario,adecisionregardingtherouteof
deliveryshouldbeindividualized. [31,36]
OperativeriskmayoutweighthepotentialbenefitoffurtherreducingHIVtransmission.InastudybyLouisetalthat
comparedtheoutcomeofcesareansectionin378womeninfectedwithHIVandinmorethan54,000uninfected
women,HIVinfectedwomenhadahigherrateofintraoperativeneedforbloodtransfusionaswellasincreased
incidenceofpostpartumendometritis,sepsis,pneumonia,admissiontotheintensivecareunit,andmaternaldeath.
[37]

IntheHIVinfectedgroup,morbidityandmortalitywereassociatedwithinfectionandrelatedtoimmunefunction,
withthegreatestriskbeingforwomenwithaCD4countlessthan200cells/mL. [37]
BecausemorbidityisincreasedinwomeninfectedwithHIVwhoundergocesareandelivery,prophylacticantibiotics
shouldbeadministered.Scheduledcesareandeliveryshouldbediscussedandrecommendedforwomenwithviral
loadsgreaterthan1000copies/mL,whetherornottheyaretakingantiretroviraltherapy.
Discussionoftheoptionofscheduledcesareandeliveryshouldbeginasearlyaspossibleinpregnancywithevery
pregnantwomaninfectedwithHIV,togiveheranadequateopportunitytoconsiderthechoiceandplanforthe
procedure.Therisks,whichappeartobegreaterforthemother,mustbebalancedwiththebenefitsexpectedfor
theneonate.Thepatient'sautonomymustberespectedwhenmakingthedecisiontoperformacesareandelivery,

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becausethepotentialformaternalmorbidityissignificant.
Consultationandfollowupwithspecialistsininfectiousdiseaseandmaternalfetalmedicineisrecommended.

DietandActivity
Duringpregnancy,ahealthy,wellbalanceddietisrecommended,andthisrecommendationisnotalteredbyHIV.
Certainfoodsneedtobelimitedandavoidedduringallpregnancies.Alcoholshouldbeavoided.Generally,eating
fishlowinmercurycontentisrecommended.Caffeinemustalsobelimited,aswellasfoodshighinnitritesandsoft
cheeses.CurrentavailableevidencesuggeststhatvitaminAsupplementationduringpregnancy(nottoexceed
10,000IUinthefirsttrimester)improvesbirthweight. [38]Lightexerciseisrecommendedinpregnancy,andthis
recommendationisnotalteredbyHIVinfection.Walkingandswimmingareexcellentprogramsduringpregnancy.
Womenshoulddiscusstheirexerciseroutinewiththeirphysician.

DeterrenceandPrevention
Currently,novaccineisavailableforHIVtherefore,preventioniscrucialtodecreasingtheriskoftransmission. [39]
Womenmustbecounseledonmethodstoavoidtransmissiontoothers,includingsafesexpracticeandavoiding
donationofbloodororgans.
Regularuseoflatexcondomsandavoidanceofunprotectedintercourseisimportant.Treatmentofgenitaltract
infectionsandinflammationinbothpartnersisimportanttoavoidmucosalbreaks.Thefrequentuseofnonoxyynol9
vaginalgelhasbeenassociatedwithincreasedriskofHIVacquisitioninthehighriskpopulation.Womenshouldnot
sharetoothbrushesorrazors,assmallamountsofbloodmaybepresent.
Inareasoftheworldwheresafealternativesareavailable,breastfeedingisnotrecommended.Thisalsoappliesto
womenonantiretroviraltherapy. [5,14]Passageofantiretroviralsintobreastmilkhasbeenshownforseveralagents,
includingzidovudineandlamivudine. [18]

ContributorInformationandDisclosures
Author
TeresaMarino,MDAssistantProfessor,AttendingPhysician,DivisionofMaternalFetalMedicine,Tufts
MedicalCenter,TuftsUniversitySchoolofMedicine,Boston,Massachusetts
Disclosure:Nothingtodisclose.
SpecialtyEditorBoard
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenter
CollegeofPharmacyEditorinChief,MedscapeDrugReference
Disclosure:MedscapeSalaryEmployment
ChiefEditor
ThomasChihChengPeng,MDProfessor(Collateral),DepartmentObstetricsandGynecology,Virginia
CommonwealthUniversitySchoolofMedicine,VCUHealthSystem
ThomasChihChengPeng,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeof
ObstetriciansandGynecologists,AmericanInstituteofUltrasoundinMedicine,andSocietyforMaternalFetal
Medicine
Disclosure:Nothingtodisclose.

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