HIV in Pregnancy
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HIV in Pregnancy Author: Teresa Marino, MD; Chief Editor: Thomas Chih Cheng Peng, MD more... Updated: Jan 15, 2015 Overview The reduction in mothertochild transmission of human immunodeficiency virus (HIV) is regarded as one of the most effective public health initiatives in the United States. In the absence of treatment, the risk of vertical transmission of HIV is as high as 2530%. With the implementation of HIV testing, counseling, antiretroviral medication, delivery by cesarean section prior to onset of labor, and discouraging breastfeeding, the motherto infant transmission has decreased to less than 2% in the United States. Before the current treatment era, approximately 2000 babies were infected with HIV each year in the United States alone. Despite increasing HIV prevalence, that figure now stands at approximately 300 infants per year. [1] The rapid clinical implementation of research findings directed toward decreasing perinatal transmission is credited as the key to this accomplishment. In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) protocol 076 demonstrated that the administration of zidovudine during pregnancy and labor and then to the newborn decreased the risk of perinatal transmission of HIV by 68%, from 25.5% to 8.3%. [2] In the late 1990s, the combined use of 3 or more antiretroviral medications was found to be highly successful at suppressing viral replication. The exact mechanism of mothertochild transmission of HIV remains unknown. Transmission may occur during intrauterine life, delivery, or breastfeeding. The greatest risk factor for vertical transmission is thought to be advanced maternal disease, likely due to a high maternal HIV viral load. [3] Unfortunately, about 30% of pregnant women are not tested for HIV during pregnancy, and another 1520% receive no or minimal prenatal care, thereby allowing for potential newborn transmission. [4] Epidemiology United States statistics Early in the acquired immunodeficiency syndrome (AIDS) epidemic, women were rarely diagnosed with HIV or AIDS, but by 2005, women represented 27% of the estimated 45,669 new diagnosis of HIV/AIDS, with the greatest rise among young women. [5] About 80% of new cases in women in the United States are contracted through heterosexual intercourse, 20% by contaminated needles, and most of the remaining cases by maternalchild transmission. Testing of donated blood has essentially eliminated blood transfusions as a source of infection. Of women with AIDS, 71% were diagnosed between the ages of 25 and 44, implying that many of them may have been infected as adolescents. In the United States, African American and Hispanic women represent 25% of the female population but account for 82% of the total number of women with AIDS. Furthermore, women of color account for 80% of newly diagnosed HIV/AIDS cases. [6] International statistics The Joint United Nations Programme on HIV/AIDS (UNAIDS) has estimated that, in 2008, approximately 33.4 million people worldwide (1% of the global adult population aged 1549 y) were infected with HIV, a decline from 2006 (39.5 million reported at that time); 67% of all people living with HIV worldwide live in subSaharan Africa, and 91% of all new infections among children occur there. [7] More than 500,000 babies worldwide contract HIV from their mothers; 90% of these cases occur in developing countries. In 2005, AIDS claimed an estimated 2.43.3 million lives; more than 500,000 of which were children. One third of these deaths were in subSaharan Africa. [5] Prophylaxis and Pregnancy Outcome The Antiretroviral Pregnancy Registry, where clinicians should report cases of exposure to antiviral therapy in pregnancy, contains approximately 5,000 reported exposures and notes no increase in the congenital malformation rate with exposure to antiretroviral medications, even in the first trimester, with the exception of efavirenz. Early exposure to efavirenz has been associated with neural tube defects. Concern was raised that antiretroviral therapy may increase the incidence of adverse pregnancy outcomes. Several studies have shown that zidovudine monotherapy had no negative effect on pregnancy. Although data from cohorts in the United States have not shown an increased risk of preterm birth with combination therapy, a European collaborative study showed an increased risk of preterm labor in women infected with HIV who were taking combination antiretroviral therapy, with an odds ratio for preterm birth of 1.8 for combination therapy without a protease inhibitor and 2.6 for combination therapy that included a protease inhibitor. [8] In a US study of pregnant women infected with HIV, the overall rate of adverse pregnancy outcome, including prematurity, low birth weight, stillbirth, and abnormal Apgar scores, was similar in women who received antiretroviral therapy during pregnancy and those who did not. [9] Of the 2123 women in the study, 1590 received monotherapy, 396 received combination therapy without a protease inhibitor, and 137 received combination therapy with a protease inhibitor; 1143 did not receive antiretroviral therapy. Rates of prematurity and extreme prematurity did not differ significantly according to antiretroviral regimen. Although the risk of low and very low birth weight was greater in the group receiving a protease inhibitor, the results
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Transcript of HIV in Pregnancy
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6/8/2015 HIVinPregnancy
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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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