HIV in Pregnancy

6/8/2015 HIVinPregnancy

http://emedicine.medscape.com/article/1385488overview 1/10

HIVinPregnancyAuthor:TeresaMarino,MDChiefEditor:ThomasChihChengPeng,MDmore...

Updated:Jan15,2015

OverviewThereductioninmothertochildtransmissionofhumanimmunodeficiencyvirus(HIV)isregardedasoneofthemosteffectivepublichealthinitiativesintheUnitedStates.Intheabsenceoftreatment,theriskofverticaltransmissionofHIVisashighas2530%.WiththeimplementationofHIVtesting,counseling,antiretroviralmedication,deliverybycesareansectionpriortoonsetoflabor,anddiscouragingbreastfeeding,themothertoinfanttransmissionhasdecreasedtolessthan2%intheUnitedStates.

Beforethecurrenttreatmentera,approximately2000babieswereinfectedwithHIVeachyearintheUnitedStatesalone.DespiteincreasingHIVprevalence,thatfigurenowstandsatapproximately300infantsperyear.[1]

Therapidclinicalimplementationofresearchfindingsdirectedtowarddecreasingperinataltransmissioniscreditedasthekeytothisaccomplishment.In1994,thePediatricAIDSClinicalTrialsGroup(PACTG)protocol076demonstratedthattheadministrationofzidovudineduringpregnancyandlaborandthentothenewborndecreasedtheriskofperinataltransmissionofHIVby68%,from25.5%to8.3%.[2]Inthelate1990s,thecombineduseof3ormoreantiretroviralmedicationswasfoundtobehighlysuccessfulatsuppressingviralreplication.

TheexactmechanismofmothertochildtransmissionofHIVremainsunknown.Transmissionmayoccurduringintrauterinelife,delivery,orbreastfeeding.Thegreatestriskfactorforverticaltransmissionisthoughttobeadvancedmaternaldisease,likelyduetoahighmaternalHIVviralload.[3]Unfortunately,about30%ofpregnantwomenarenottestedforHIVduringpregnancy,andanother1520%receivenoorminimalprenatalcare,therebyallowingforpotentialnewborntransmission.[4]

Epidemiology

UnitedStatesstatistics

Earlyintheacquiredimmunodeficiencysyndrome(AIDS)epidemic,womenwererarelydiagnosedwithHIVorAIDS,butby2005,womenrepresented27%oftheestimated45,669newdiagnosisofHIV/AIDS,withthegreatestriseamongyoungwomen.[5]About80%ofnewcasesinwomenintheUnitedStatesarecontractedthroughheterosexualintercourse,20%bycontaminatedneedles,andmostoftheremainingcasesbymaternalchildtransmission.Testingofdonatedbloodhasessentiallyeliminatedbloodtransfusionsasasourceofinfection.

OfwomenwithAIDS,71%werediagnosedbetweentheagesof25and44,implyingthatmanyofthemmayhavebeeninfectedasadolescents.IntheUnitedStates,AfricanAmericanandHispanicwomenrepresent25%ofthefemalepopulationbutaccountfor82%ofthetotalnumberofwomenwithAIDS.Furthermore,womenofcoloraccountfor80%ofnewlydiagnosedHIV/AIDScases.[6]

Internationalstatistics

TheJointUnitedNationsProgrammeonHIV/AIDS(UNAIDS)hasestimatedthat,in2008,approximately33.4millionpeopleworldwide(1%oftheglobaladultpopulationaged1549y)wereinfectedwithHIV,adeclinefrom2006(39.5millionreportedatthattime)67%ofallpeoplelivingwithHIVworldwideliveinsubSaharanAfrica,and91%ofallnewinfectionsamongchildrenoccurthere.[7]

Morethan500,000babiesworldwidecontractHIVfromtheirmothers90%ofthesecasesoccurindevelopingcountries.In2005,AIDSclaimedanestimated2.43.3millionlivesmorethan500,000ofwhichwerechildren.OnethirdofthesedeathswereinsubSaharanAfrica.[5]

ProphylaxisandPregnancyOutcomeTheAntiretroviralPregnancyRegistry,wherecliniciansshouldreportcasesofexposuretoantiviraltherapyinpregnancy,containsapproximately5,000reportedexposuresandnotesnoincreaseinthecongenitalmalformationratewithexposuretoantiretroviralmedications,eveninthefirsttrimester,withtheexceptionofefavirenz.Earlyexposuretoefavirenzhasbeenassociatedwithneuraltubedefects.

Concernwasraisedthatantiretroviraltherapymayincreasetheincidenceofadversepregnancyoutcomes.Severalstudieshaveshownthatzidovudinemonotherapyhadnonegativeeffectonpregnancy.

AlthoughdatafromcohortsintheUnitedStateshavenotshownanincreasedriskofpretermbirthwithcombinationtherapy,aEuropeancollaborativestudyshowedanincreasedriskofpretermlaborinwomeninfectedwithHIVwhoweretakingcombinationantiretroviraltherapy,withanoddsratioforpretermbirthof1.8forcombinationtherapywithoutaproteaseinhibitorand2.6forcombinationtherapythatincludedaproteaseinhibitor.[8]

InaUSstudyofpregnantwomeninfectedwithHIV,theoverallrateofadversepregnancyoutcome,includingprematurity,lowbirthweight,stillbirth,andabnormalApgarscores,wassimilarinwomenwhoreceivedantiretroviraltherapyduringpregnancyandthosewhodidnot.[9]Ofthe2123womeninthestudy,1590receivedmonotherapy,396receivedcombinationtherapywithoutaproteaseinhibitor,and137receivedcombinationtherapywithaproteaseinhibitor1143didnotreceiveantiretroviraltherapy.

Ratesofprematurityandextremeprematuritydidnotdiffersignificantlyaccordingtoantiretroviralregimen.Althoughtheriskoflowandverylowbirthweightwasgreaterinthegroupreceivingaproteaseinhibitor,theresults

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didnotreachstatisticalsignificance.Furthermore,thismaybeareflectionofhigherviralloadoradvancedstageofdiseaseratherthanexposuretoproteaseinhibitors.[9]

Inamorerecentretrospectivestudy(20042012)thatevaluatedUSinfantgrowthpatternsduringtheirfirstyearoflifeamongthoseborntoperinatallyHIVinfected(PHIV)(32infants,25mothers)andnonperinatallyHIVinfected(NPHIV)mothers(120infants,99mothers)whoreceivedcare,infantsofPHIVmothershadlowermeanlengthforagezscores(LAZ)thatwereassociatedwithbirthlength.Othersmallforgestationalageanthropometricparameterassociationsincludedthoseofbirthweightandweightforagezscores(WAZ)andthoseofbothbirthlengthandweightwithweightforlengthzscores(WLZ).TheinvestigatorsalsoreportedanassociationbetweendeliveryHIVRNAlevelbelow400copies/mLwithincreasedWAZandWLZ.[10]

Alargemetaanalysisthatincludedarticlesfromseveralcountriesbetween1998and2006showedthatoverall,highlyactiveantiretroviraltherapy(HAART)didnotincreasetheriskofprematurityhowever,theuseofregimenswithproteaseinhibitorsseemedtoincreaseprematurityslightly.[11]

ApossibleassociationexistsbetweenHAARTandpreeclampsia.[12]

ThedevelopmentofglucoseintolerancemaybemorecommoninpregnantwomenwithHIV.Originallythoughttobeassociatedwithproteaseinhibitors,gestationaldiabetesappearstobesomewhatincreasedregardlessofthemedicationregimen.Assuch,duringpregnancy,womenshouldbescreenedandmonitoredforglucoseintolerance.[13]

HIVandPregnancyPlanningPreliminarydatasuggestthatwomenwithHIVmaysufferfromsubfertility.Conceptionincoupleswhohaveneverconceivedmayoccurinamedianof6monthswith2actsofintercourseduringtheovulatoryperiodofthecycle.Witheachact,theriskofsexualtransmissionmustbeconsideredeveninthepresenceofanundetectableviralload.ConductingtestingandconsideringreproductivetechniquesinwomeninfectedwithHIVmaybeworthwhileinanefforttoreducetheriskofinfectiontoahealthypartner.

Incouplesplanningapregnancywhereonlythemalepartnerisinfected,naturalconceptioncarriesariskofsexualtransmissiontotheuninfectedfemale.CounselingprovidedtosuchcouplesshouldincludestrategiestominimizeHIVtransmission.Optionsincludeadoption,spermdonation,andassistedreproductiontechniques.Whileantiretroviraltherapycanreduceviralloadinthebloodtoundetectablelevels,somereportshaveshownthatmencanstillhaveasubstantialviralconcentrationinsemeninthepresenceofanundetectableplasmaviralload.

Whenpossible,confirmationofundetectableseminalplasmaviralloadmaybeconsidered.IfHIVviralloadcannotbesuppressed,semenwashinghasbeenproposedandmaydecreasetheHIVRNAandDNAtoundetectablelevels.Afterprocessingandrecheckingforresidualcontamination,thespermatozoacanbeusedforintrauterineinseminationorinvitrofertilization.

PregnancydoesnotappeartoinfluencetheprogressionofHIVdisease.[14,15]AlargecohortofFrenchwomenwithknownseroconversiondatesnotedapregnancyadjustedrelativeriskofprogressionfromHIVtoAIDSof0.7.[16]Furthermore,pregnancydoesnotseemtoaffectsurvivalofwomeninfectedwithHIV.[17]

Forserodiscordantcoupleswhowanttoconceive,theuseofantiretroviraltherapy(ART)isrecommendedfortheHIVinfectedpartner,withthestrengthoftherecommendationdifferingbasedontheCD4cellcountoftheinfectedpartner.Additionally,NIHguidelinesincludediscussionregardingpreexposureprophylaxis(PrEP)studiesinheterosexualcouples.NewrecommendationsregardingpericonceptionadministrationofantiretroviralPrEPforHIVuninfectedpartnersmayofferanadditionaltooltoreducetheriskofsexualtransmission.Theguidelinesincludeinformationoncounseling,laboratorytesting,andmonitoringofindividualsonPrEPandtheimportanceofreportinguninfectedwomenwhobecomepregnantonPrEPtotheAntiretroviralPregnancyRegistry.[18,19,20]

HIVinfectionriskreductionstrategiesinconjunctionwithrelativelyinexpensivefertilityawarenessmethods(FAMs)maybeusefulforcounselingHIVserodiscordantcoupleswhowanttoconceive.[21]Suchmethodsincludeuseofaccessibleandhighlysensitive,butpoorlyspecific,strategieslikethecalendarmethod,basalbodytemperaturemeasurements,andcervicovaginalmucussecretionfeatures.Urinaryluteinizinghormonetestinghashighspecificityandcostwithlesssensensitivity.Timedcondomlesssexhaslowcostbutnecessitatesunderstandinghowtopreciselypredictthefertileperiodinamenstrualcycle.[21]

PatientEducationApproximately30%ofwomenintheUnitedStatesarenottestedforHIVduringpregnancy.Reasonsfordecliningshouldbeexploredandpatientscounseledappropriately.Testingstrategiesalsoincludereofferingscreeninginthethirdtrimestertowomenwhodeclinedfirsttrimesterscreeningorwhoareinhighriskgroups.TheCentersforDiseaseControlandPrevention(CDC)recommendsroutinethirdtrimesterscreeninginwomenwithhighriskbehaviorsorwhoexhibitsignsorsymptomsofthedisease.[4]

ClinicianswhocareforwomenwithHIVneedtoprovidefamilyplanningservicesandcounselingregardingoptimizinghealthstatus.Thisincludesencouragingcompliancetomedicationregimens,cessationofsmoking,andupdatingimmunizations.

Stressingtheimportanceoftakingtheirmedicationregularlytodecreasethepossibilityofthedevelopmentofantiretroviraldrugresistancemayencouragewomentocomplywiththerapy.Cigarettesmoking,concurrentuseofdrugs(cocaine,heroin),andunprotectedintercoursehavebeenassociatedwithincreasedriskofperinataltransmission.

Itisencouragingtonotetherehasbeenasubstantialreductioninsubstanceuseinthepast2decades.[22]Inaretrospectivestudyovera23yearperiod(19902012)thatevaluateddatafromtwoprospectivecohortstudies(WomenandInfantsTransmissionStudy,SurveillanceMonitoringforAntiretroviralTherapyToxicitiesStudy),investigatorsnotedadramaticdecreaseinsubstanceuseamong5451HIVinfectedpregnantwomen(1990:82%2012:23%).Therewasasignificantdeclineinuseofeachsubstancebetween1990and2006,whenitreachedaplateau,whichtheinvestigatorssuggestedmayhavebeencausedbyanepidemiologictransitionoftheHIVepidemicamongUSwomen.[22]Substanceusewasinverselyassociatedwithreceivingantiretroviraltherapy.Womenwithmultiplepregnancieswithsubstanceuseintheirpreviouspregnancywereathigherriskofsubstance

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useintheirnextpregnancy.[22]

Unfortunately,15%ofwomeninfectedwithHIVreceivenoorminimalprenatalcare,and20%donotinitiateprenatalcareuntillateinthethirdtrimester.Womenwhoarenottreatedduringpregnancyshouldbetreatedwithoneoftheappropriateintrapartumantiretroviraldrugregimens.

Evenintheabsenceofantepartumtreatment,intrapartumandearlyneonatalprophylaxiscanreducethemothertochildtransmissionrisk.Womenshouldbeextensivelycounseledregardingtheabilitytodecreasetheriskofperinataltransmissionwithhighlyactiveantiretroviraltherapy(HAART)prophylaxisortreatment.InwomenwhoarebeingtreatedwithHAARTandplanningapregnancy,theteratogenicpotentialofcertainantiretroviralmedicationsmustbereviewedandeffectivecontraceptiondiscussed.Thesemedicationsshouldbestoppedpriortoplanningapregnancy.

HistoryandPhysicalExamination

History

Inpregnancy,theinitialhistoryshouldassessthestatusofthepatientsHIVdisease(eg,CD4+Tcellcount,viralload),theneedforbeginningoralteringantiretroviralmedication,andwaystoreduceperinataltransmission.Acarefulreviewofthemedicalandsurgicalhistory,gynecologichistory,highriskhabits,andpreviousobstetrichistoryshouldbedoneatthefirstprenatalvisit.

Physicalexamination

Duringpregnancy,acompletephysicalexaminationmustbeperformed.Knowledgeofthenormalphysiologicchangesofpregnancy,suchasanenlargedthyroidglandandasystolicmurmur,isimportanttodifferentiatefromdiseaseprocess.HIVinfectioncanaffectessentiallyallbodysystems.

ScreeningTheAmericanCongressofObstetricsandGynecology(ACOG)recommendsroutineHIVscreeningforwomenaged1964yearsandtargetedscreeningforatriskwomenoutsideofthisagereference.AllpregnantwomenshouldhavetheirHIVserostatusevaluatedwhentheyfirstpresentforprenatalcare.

WomenshouldhavetherighttorefusetestingafterbeinginformedthatHIVtestingwillbedrawnaspartoftheirroutineprenatalpanel.Thisoptoutapproachtoprenatalscreening,asadvocatedbytheInstituteofMedicine,isassociatedwithhighertestingratesamongpregnantwomen.However,severalstateshavelawsthatprohibitthisapproachandmandatethatpatientssignconsentformsfortesting,knownastheoptinapproach.[23]

ELISA

Themostcommonscreeningtestisanenzymelinkedimmunosorbentassay(ELISA),whichlooksforthepresenceofantibodies.Ifthistestresultispositive,theELISAisrepeatedtoeliminatelaboratoryerrorpriortoproceedingtoaconfirmatorytestbyWesternblot.TheELISAhas98%sensitivity.Falsenegativeresultsmayoccurearlyinthedisease,andfalsepositiveresultshavebeenreportedaftercertainvaccines.Repeattestingseveralmonthslaterusuallyconfirmsseronegativityinsuchcases.ApositivetestissentforWesternblot.

Westernblot

FortheWesternblot,specificviralproteinsareseparatedbyelectrophoresis,andreactionofantibodyto3proteinsmustoccurforthetesttobeconsideredpositive.Indeterminateresultsoccurwhen1or2oftheproteinsarepresent.Inlowriskpopulations,indeterminateresultsusuallyreverttonegativeoverseveralmonths.Westernblothasafalsepositiverateof1in20,000.

Bloodcountsandviralload

ForpregnantwomeninfectedwithHIV,inadditiontothestandardprenatalassessment,continuedassessmentofHIVstatusisimportant.Acompletebloodcounttoassessanemiaandwhitebloodcellcountaswellasrenalandliverfunctiontestsshouldbeincluded.InitialevaluationincludesCD4+counts,whichhelpdeterminethedegreeofimmunodeficiency.

Viralload,determinedbyplasmaHIVRNAcopynumber(copies/mL)assessestheriskofdiseaseprogression.Theviralloadisimportantindecisionsregardingmaternaltreatmentanddeliverymanagementhowever,becauseperinatalHIVtransmissioncanoccurevenatloworundetectableHIVRNAcopynumbers,theviralloadisnotusedinpregnancytodecidewhethertostartantiretroviralmedications.

Ifaviralloadisdetected,antiretroviraldrugresistancestudies(HIVgenotype)shouldbeperformedbeforestartingtherapyunlessthediagnosisismadelateinthepregnancy,inwhichcasestartingmedicationswhileawaitingresultsisrecommended.Ingeneral,pregnancyhasnotbeenassociatedwithariskofrapidprogressionofHIV.[17]

Withappropriatetherapy,theviralloadshoulddropby1logwithinthefirstmonthandbecomenondetectablewithin6monthsafterinitiatingtreatment.Thehighertheviralload,thelongerthedecreasemaytakehowever,iftheviralloadpersistsorincreasesat6months,treatmentfailuremustbeconsidered.

Lipidprofileandultrasound

Otherlaboratorystudiesshouldincludealipidprofile,whichisnotusuallyobtainedinpregnancy.Althoughcholesterolnormallyincreasesinpregnancy,baselinevaluesarerequired,ascertainmedicationshavebeenassociatedwithincreasedtriglycerideandcholesterollevels.Evaluationofotherinfectiousdiseasestatesandpossibleopportunisticinfections,suchassyphilis,cytomegalovirus,andtoxoplasmosis,alsoneedstobedone.

Initialobstetricultrasonographyforviabilityanddatingisimportantfordeterminingtreatmentandplanningdelivery.Potentialteratogenicityishighestduringthefirsttrimester,andsomepatientsmayconsiderdelayingtreatmentuntilafterthefirst12weeksofpregnancy.Inwomenwhoareseverelyill,therisksandbenefitsofthisdelaymustbeweighed.Atargetedultrasonographymaybewarranteddependingonmedicationexposure.

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Hepatitistesting

HepatitisBsurfaceantigenstatusisrecommendedforallpregnantwomen.InthecaseofacutehepatitisBinfection(HBV),theriskofverticaltransmissionalsovarieswithgestationalage,withan8090%riskoftransmissiontotheoffspringiftheinfectionoccursinthethirdtrimester.[23]WomenwhoarecoinfectedwithHIVandchronichepatitisBmayrequiredifferentmanagementinpregnancy.

CoinfectionwithHIVandhepatitisCvirus(HCV)iscommonandmayrangefrom1754%.[24]ThediagnosisofhepatitisCisconfirmedbyidentificationofthehepatitisCantibodyviaanELISAtest.FalsenegativeHCVtestresultsmayoccuriftheCD4countisverylow.Morespecifictests,(eg,hepatitisCviralRNAdetectionbypolymerasechainreaction)areavailable.Highmaternalviraltitershavebeenassociatedwithanincreasedriskofverticaltransmission.

AllwomenwhoarechroniccarriersofHBVorHCVshouldinformsexualpartners,householdcontacts,andneedlesharingcontactsandreviewprecautionstodecreasetransmission.

Opportunisticinfectionassessment

AssessmentoftheneedforprophylaxisagainstPneumocystisjirovecipneumonia(PCP)orMycobacteriumaviumcomplex(MAC)infectionisnecessary.ForwomenwithlowCD4counts,prophylaxisforPCPiswithtrimethoprimsulfamethoxazole(TMPSMX).Duetopotentialteratogenicity,aerosolizedpentamidinemaybesubstitutedinthefirsttrimester,asitisnotabsorbedsystemically.ForprophylaxisofMAC,azithromycinisusedinplaceofclarithromycinbecauseofpotentialteratogenicity.[14]

Othersexuallytransmitteddiseasetesting

Screeningforothermaternalsexuallytransmitteddiseasesisrecommendedinpregnancy.Forexample,screeningformaternalsyphilisisimportantnotonlyforthepreventionofcongenitalsyphilisbutalsobecausematernalsyphilishasbeenassociatedwithanincreasedriskofmothertochildtransmissionofHIV.[25]

Vaginalspeculumexaminationshouldbeperformedtoobtaincervicalcytologysmearandassaysforgonorrheaandchlamydia.Allsexuallytransmitteddiseasesshouldbetreatedpromptly.GenitalwartsandvulvarintraepithelialneoplasiaaremorecommonamongHIVseropositivethanHIVseronegativewomen,butwartregressionisascommoninwomenwithHIVasthosewithoutandcancerisinfrequent.[26]WomeninfectedwithHIVhaveahigherincidenceofcervicaldysplasia.

Vaccination

Vaccinationsshouldbekeptupdated.Duringpregnancy,liveattenuatedvaccines(eg,measlesmumpsrubella[MMR],varicellavaccines)shouldbeavoided.AnnualinfluenzavaccineandpneumococcalvaccineshouldbeadministeredtoallpregnantwomenwhoareHIVpositive.TheH1N1influenzavaccineshouldbeadministeredtoallpregnantwomenandissafeinwomenwithHIV.

Tuberculosistesting

CoinfectionwithHIVandtuberculosisisverycommonindevelopingnations.ImmunosuppressionfromHIVinfectioncontributesnotonlytoahigherrateoftuberculosisreactivationbutalsotoanincreaseddiseaseseverity.

Tuberculosisskintestingshouldbeperformedanda5mmpurifiedproteinderivative(PPD)resultinterpretedaspositive.Ifpositive,chestradiographycanbeperformedduringpregnancybecauseradiationriskisexceedinglylow.

Presentationduringlabor

Forwomenwhopresentinlaborandhavenothadprenataltesting,rapidtestingshouldbeoffered.UnliketheELISA,therapidHIVtestisabloodorsalivaantibodytestandresultsareusuallyavailablewithinanhour.Therapidtestisreportedtohaveahighnegativepredictivevalue(100%)andtobehighlysensitiveandspecific(approaching100%)however,thepositivepredictivevalueinpregnancyvariesfrom44100%.[4]PatientswhotestpositiveinlaborbyELISAshouldbetreatedasHIVpositiveuntilconfirmatoryresultsareavailable.

AntiretroviralTherapy

Overview

Mothertochildtransmissionislinkedtoviralload.Assuch,antiretroviraltherapyshouldbeofferedtoallpregnantwomeninfectedwithHIVtoreducetheriskofperinataltransmissiontobelow2%.[27]Combinationantiretroviraltherapyshouldbeofferedinallcases.Aszidovudine(ZDV)istheonlyagentspecificallyshowntoreduceperinataltransmission,itshouldbeusedwheneverpossibleaspartofthehighlyactiveantiretroviraltherapy(HAART)regimen.[2]

Ifapregnantwomanhasreceivedantiretroviralmedicationinthepastbutisnotcurrentlyonanymedication,thechoiceofregimenmayvaryaccordingtothehistoryofprioruse,theindicationforstoppingtreatmentinthepast,gestationalage,andresistancetesting.Inthissetting,ifthereisnoresistancetothedrugsandtheregimensuppressedviralload,antiretroviralmedicationcanbeusedagain,butavoiddrugswithteratogenicpotentialoradversematernaleffects.

IfapatientwhoisonaHAARTregimenpresentsforprenatalcare,continuinghertreatmentduringthefirsttrimesterisreasonable,providedthatcareistakentoavoidmedicationsthatarecontraindicatedinearlypregnancy.HIVantiretroviraldrugresistancetestingisrecommendedifaviralloadisdetectable.Considerationsofdrugsnotusuallyusedearlyinpregnancymaybenecessaryifdrugresistanceisconfirmedandthepatientreceivesextensivecounselingregardingriskandbenefits.

InanHIVinfectedpregnantwomanwhohasneverbeenexposedtoantiretroviralmedication,HAARTshouldbestartedassoonaspossible,includingduringthefirsttrimester.Again,recommendationsarefordrugresistancetestingandcaretoavoidmedicationsthatmaypotentiallycauseadversematernalandfetaleffects.

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IfprenatalHIVtestingwasnotperformedandarapidHIVtestreturnspreliminarilypositive,thepatientshouldbetreatedlikeanyotherwomaninfectedwithHIV.Certainly,thegestationalageandobstetricalscenariomaydictatethetreatmentoptionsavailable,butastheexposurerisktoantiretroviralmedicationisminimaltobothmotherandfetus,antiretroviraltherapyshouldbeinitiated.[4]

Thepatientwithapositiverapidtestmustbecounseledregardingthepossibilityofafalsepositivescreen,andtheresultsshouldbedocumentedaspreliminaryinthemedicalchart.Ifthistestwasperformedonarrivalinlabor,treatmentwiththeZDVprotocolthroughlaborisrecommended,followedbyadministrationtotheneonateuntilconfirmatorytestingonthemotherbecomesavailable.

Antiretroviralregimens

TreatmentofwomeninfectedwithHIVshouldnotbewithheldbecauseofpregnancy.Althoughthedecisionregardingstartingormaintainingcurrentantiretroviraltherapyisbasedonthesamecriteriaasinnonpregnantpatients,severalconsiderationsmustbetakenintoaccountbecauseofpotentialeffectsonthefetus.

Theuseofthe3partZDVprophylaxisregimen,aloneorincombinationwithotherantiretroviralmedications,shouldbediscussedandofferedtoallpregnantwomenbecauseZDVwasthefirstagenttoshowsignificantdecreaseinthemothertochildtransmissionofHIV.[2]Theregimenchosenshouldalsotakeintoaccountpriortherapyandresponsetothatregimen,aswellasresistancetesting.Gestationalageandpotentialfetalandneonataltoxicitymustalsobetakenintoaccountwhenselectingaregimen.

Themechanismofactionwithwhichthesedrugsreduceperinataltransmissionincludesloweringmaternalviralloadhowever,asthesedrugscrosstheplacenta,thereappearstobeprenatalprophylaxisaswell.Thethirdcomponent,prophylaxisofthenewborn,furtherdecreasestheriskofperinataltransmission.

Theantiretroviraldrugsusedinpregnancyfallbroadlyinto3categories:thenucleosideandnucleotideanaloguereversetranscriptaseinhibitors(NRTIs),nonnucleosidereversetranscriptaseinhibitors(NNRTIs),andproteaseinhibitors(PIs).Thereareinsufficientdatatoallowrecommendationsregardingtheuseofentryinhibitorsorintegraseinhibitorsinpregnancy.

GuidelinesforperinatalARTwererevisedinJuly2012regardingwhichagentsareconsideredpreferred,alternative,ortobeusedunderspecialcircumstances.Combinationregimens,usuallyincluding2NRTIswitheitheranNNRTIor1ormoreproteaseinhibitors(PIs)arerecommended.Forfurtherinformation,seeTable1.

Table1.ARTagentsduringpregnancy[18](OpenTableinanewwindow)

ARTClass Preferred* Alternate SpecialCircumstances InsufficientDatatoRecommendNRTIs zidovudine(ZDV)

lamivudine(3TC)

abacavir

emtricitabine

tenofovir

didanosine

stavudine

NNRTIs nevirapine efavirenz etravirine

rilpivirine

PIs atazanavir

lopinavir+ritonavir

ritonavir

darunavir

saquinavir

indinavir

nelfinavir

fosamprenavir

tipranavir

FusionInhibitors enfuvirtide

maraviroc

IntegraseInhibitors

raltegravir

*ZDVplus3TCisarecommendeddualNRTIbackboneregimenplusanNNRTIand1ormorePIsforpregnantwomenwithHIV

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Nucleotideanaloguereversetranscriptaseinhibitors

TheNRTIsaregenerallywelltoleratedandcrosstheplacenta.TheFDAhasclassifiedtheseaspregnancyclassBorC,dependingontheagent.ThesedrugsdobindtomitochondrialDNAgammapolymeraseandmaycausemitochondrialdysfunctionmanifestingascardiomyopathy,neuropathy,lacticacidosis,andliverdysfunction.Geneticsusceptibilitytothesedrugsmayplayarole,andtheeffectsusuallyresolvewithcessationofthemedication.[1]

ThecombinationofdidanosineandstavudinehasbeenassociatedwithlacticacidosisandhepaticfailureleadingtofatalitiesandshouldbeusedwithcautionoronlyincaseswhereotherNRTIscannotbeusedduetoresistanceortoxicity.Finally,ZDVandstavudinehaveoverlappingtoxicitiesandareantagonisticandshouldbeavoidedincombination.[27]

Nonnucleosidereversetranscriptaseinhibitors

FiveNNRTIsareFDAapproved:delavirdine(Rescriptor),efavirenz(Sustiva),etravirine(Intelence),nevirapine(Viramune),andrilpivirine(Edurant).AlthoughlessinformationisavailableregardingNNRTIuseinpregnancy,nevirapineandefavirenzbothcrosstheplacenta.Themostcommonsideeffectisrash,whichcanoccurinupto17%ofpatientsonnevirapine.[14]

Useofefavirenzisnotrecommendedinthefirsttrimesterbecauseofreportedcasesoffetalneuraltubedefects.TheFDAhaschangedthepregnancyclassificationofthisdrugtocategoryD.[28]

Severenevirapineassociatedskinrashandhepatictoxicityhavebeenreportedinpregnancy.Thepotentiallyfatalhepatotoxicityappearstobeincreasedinwomen,duringpregnancy,andinpatientswithaCD4+Tcellcountgreaterthan250cells/mL.Becauseofthesesignificantcomplications,nevirapineshouldnotbeusedasfirstlinetherapyunlessnootheroptionisavailable.

InwomenwhoseCD4+Tcellcountswerebelow200cells/mLandwhowerepreviouslyexposedtoperipartumsingledosenevirapine,ritonavirboostedlopinavirplustenofoviremtricitabinewassuperiortonevirapineplustenofoviremtricitabineforinitialantiretroviraltherapy.[29]

InchildrenpreviouslyexposedtosingledosenevirapineforperinatalpreventionofHIVtransmission,zidovudineandlamivudineplusritonavirboostedlopinavirforantiretroviraltreatmentresultedinbetteroutcomesthantreatmentwithzidovudineandlamivudineplusnevirapine.[30]

Proteaseinhibitors

Proteaseinhibitorsdonotcrosstheplacentaeasily,andnoteratogeniceffectshavebeennotedinanimals.TheyareclassifiedasclassBorCbytheFDA.

AlsoseetheMedscapeDrugs&DiseasestopicAntiretroviralTherapyforHIVInfection.

PeripartumTreatmentInanypregnantwomaninfectedwithHIVwhopresentsinlabor,whetherherHIVpositivestatuswaspreviouslyknownorwasdeterminedbyrapidtestresult,morethanonetreatmentoptionisavailableduringlaboranddelivery.AllHIVinfectedwomenwithHIVRNA400copies/mL(orunknownHIVRNA)neardeliveryshouldbeadministeredIVzidovudine(ZDV)duringlabor,regardlessofantepartumregimenormodeofdelivery.IVZDVisnolongerrequiredforHIVinfectedwomenreceivingcombinationARTregimenswhohaveHIVRNA

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ARTatthefollowingweightsanddosages:

Birthweight1.52kg:8mg/dosePOBirthweight>2kg:12mg/dosePO

Administer3dosesinthefirstweekoflife1stdose48hoursafterbirth,give2nddose48hoursafter1stdose,and3rddose96hoursafter2nddose.

HepatitisCoinfectionThecurrentrecommendationfortreatingwomencoinfectedwithHIVandHBVistotreatthesewomenwithtenofovirandlamivudineoremtricitabine.[32]All3haveshownactivityagainstHBV.Ametaanalysisfoundthattheuseoflamivudineeffectivelypreventsmothertochildtransmission,eveninpregnantwomenwhohaveahighdegreeofHBVinfectiousnessinlatepregnancy.[33]

Althoughdataareinsufficientfortheuseoftenofovirinpregnancy,thebenefitslikelyoutweightherisksinwomenwithHBV/HIVcoinfection.Womenreceivingtreatmentshouldbeadvisedofthesignsandsymptomsoflivertoxicity,andregularfollowupoftransaminaselevelsiswarranted.TheinfantshouldreceivehepatitisBimmunoglobulinandstartthe3doseseriesofhepatitisBvaccinewithinthefirst12hoursoflife.[18]

PregnancydoesnotappeartoalterthecourseofHCVinfectionhowever,coinfectionwithHIVdoesappeartoincreasetheriskofperinataltransmissionofHCV.Assuch,a3drugantiviralcombinationisrecommendedregardlessoftheviralload.AswithHBVcoinfection,patientsshouldbemadeawareofthesignsandsymptomsoflivertoxicity,andtransaminasesshouldbefollowedevery24weeks.

AswithHIV,prolongedruptureofmembranesmayincreasetheriskofperinatalHCVtransmissionhowever,thedataremaininconclusiveregardingtheuseofcesareansectiondeliverytodecreasetheriskoftransmission.Assuch,deliveryrecommendationsarebasedontheHIVstatus.InfantscanbeevaluatedbytestingHCVRNAat2and6monthsofageorHCVantibodyafter15monthsofage.[18]

CesareanDeliveryCesareandeliverymustbediscussedandthepatientcounseledregardingthepossibilityofanunnecessarysurgicalprocedureshouldthefinalHIVresultbenegative.[18]Careshouldbeindividualizedaccordingtoclinicalscenario.

Earlystudiesregardingcesareandeliveryandtransmissionriskshowedconflictingresults.Cesareandeliverybeforetheonsetoflabormaypreventmicrotransfusionthatoccurswithuterinecontractions,andavoidingvaginaldeliveryeliminatesexposuretovirusinthecervicovaginalsecretionsandbloodattimeofdelivery.

Inthelate1990s,prospectivecohortstudiesnotedadecreaseinmothertochildtransmissioninwomenonzidovudine(ZDV)whounderwentelectivecesareandeliverycomparedwithwomenwhodidnottakeZDVprophylaxis.[34,35]In1999,resultsfromalargemetaanalysisofindividualpatientdatafrom15prospectivecohortstudiesdemonstrateda50%reductionofverticaltransmissionwiththeuseofelectivecesareandeliveryforwomenwithHIV,afteradjustingforantiretroviraltherapy,maternalstageofdisease,andinfantbirthweight.

Ofnote,verticaltransmissionriskdidnotchangewhenthestudygroupwaslimitedtothosewomenwhohadruptureofmembranesshortlybeforesurgery.Thetransmissionriskwasdecreasedbyabout80%forwomenwhohadbothanelectivecesareandeliveryandweretakingantiretroviralmedication.[36]

Inthesameyear,ACOGissuedanopinionthatelectivecesareandeliveryshouldbediscussedandofferedtoallpregnantwomenwhowereHIVpositiveat38weeksgestationtoavoidthepotentialriskofspontaneouslaborandruptureofmembranes.[31]

ThesestudiesdidnotadjustforviralloadandwereperformedbeforeHAARTcameintouse.InpatientsonHAARTwithanundetectableviralload(

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becausethepotentialformaternalmorbidityissignificant.

Consultationandfollowupwithspecialistsininfectiousdiseaseandmaternalfetalmedicineisrecommended.

DietandActivityDuringpregnancy,ahealthy,wellbalanceddietisrecommended,andthisrecommendationisnotalteredbyHIV.Certainfoodsneedtobelimitedandavoidedduringallpregnancies.Alcoholshouldbeavoided.Generally,eatingfishlowinmercurycontentisrecommended.Caffeinemustalsobelimited,aswellasfoodshighinnitritesandsoftcheeses.CurrentavailableevidencesuggeststhatvitaminAsupplementationduringpregnancy(nottoexceed10,000IUinthefirsttrimester)improvesbirthweight.[38]Lightexerciseisrecommendedinpregnancy,andthisrecommendationisnotalteredbyHIVinfection.Walkingandswimmingareexcellentprogramsduringpregnancy.Womenshoulddiscusstheirexerciseroutinewiththeirphysician.

DeterrenceandPrevention

Currently,novaccineisavailableforHIVtherefore,preventioniscrucialtodecreasingtheriskoftransmission.[39]Womenmustbecounseledonmethodstoavoidtransmissiontoothers,includingsafesexpracticeandavoidingdonationofbloodororgans.

Regularuseoflatexcondomsandavoidanceofunprotectedintercourseisimportant.Treatmentofgenitaltractinfectionsandinflammationinbothpartnersisimportanttoavoidmucosalbreaks.Thefrequentuseofnonoxyynol9vaginalgelhasbeenassociatedwithincreasedriskofHIVacquisitioninthehighriskpopulation.Womenshouldnotsharetoothbrushesorrazors,assmallamountsofbloodmaybepresent.

Inareasoftheworldwheresafealternativesareavailable,breastfeedingisnotrecommended.Thisalsoappliestowomenonantiretroviraltherapy.[5,14]Passageofantiretroviralsintobreastmilkhasbeenshownforseveralagents,includingzidovudineandlamivudine.[18]

ContributorInformationandDisclosuresAuthorTeresaMarino,MDAssistantProfessor,AttendingPhysician,DivisionofMaternalFetalMedicine,TuftsMedicalCenter,TuftsUniversitySchoolofMedicine,Boston,Massachusetts

Disclosure:Nothingtodisclose.

SpecialtyEditorBoardFranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollegeofPharmacyEditorinChief,MedscapeDrugReference

Disclosure:MedscapeSalaryEmployment

ChiefEditorThomasChihChengPeng,MDProfessor(Collateral),DepartmentObstetricsandGynecology,VirginiaCommonwealthUniversitySchoolofMedicine,VCUHealthSystem

ThomasChihChengPeng,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofObstetriciansandGynecologists,AmericanInstituteofUltrasoundinMedicine,andSocietyforMaternalFetalMedicine

Disclosure:Nothingtodisclose.

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