HIVdanInfeksiOportunistik:PilihanTerapidanPrognosis

YudiantoBudiSaroyoFakultasKedokteranUniversitasIndonesia/

RSUPNdr.CiptoMangunkusumo

TopikPembicaraan

Epidemiologi Patofisiologi InfeksiOportunistik ProfilaksisdanTerapi Pencegahan Kesimpulan

Sumber:HIV/AIDSReport,WHOSEARO,2010.In:PedomannasionalpencegahanpenularanHIVdariibukeanak.Edisikedua.KementerianKesehatanRI,Jakarta,2011

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JumlahHIVdanAIDSyangDilaporkanperTahunsdMaret2013

Sumber:LaporanHIVAIDSTriwulan12013.DirektoratJenderalPengendalianPenyakitDanPenyehatanLingkungan(P2ML)KementerianKesehatan,2014

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SepuluhProvinsiyangMelaporkanJumlahKumulatifAIDSTerbanyakTahun1987 2013

Sumber:LaporanHIVAIDSTriwulan12013.DirektoratJenderalPengendalianPenyakitDanPenyehatanLingkungan(P2ML)KementerianKesehatan,2014

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Sumber:PemodelanMatematikEpidemiHIV,Kemkes,2012.In:PedomannasionalpencegahanpenularanHIVdariibukeanak.Edisikedua.KementerianKesehatanRI,Jakarta,2011

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AtlasofSexuallyTransmittedDiseasesandAIDS4thEd,14HumanImmunodeficiencyVirusInfectionandtheAcquiredImmunodeficiencySyndrome,StephenA.Morse,240255,2010

HIV1virionstructure

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TheHIVreplicationcycle

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,130AntiretroviralTherapyforHumanImmunodeficiencyVirusInfection,JohnE.Bennett,16221641.e6,2015

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EffectofHIVonimmunesystem

AtlasofSexuallyTransmittedDiseasesandAIDS4thEd,14HumanImmunodeficiencyVirusInfectionandtheAcquiredImmunodeficiencySyndrome,StephenA.Morse,240255,2010

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Hunter'sTropicalMedicineandEmergingInfectiousDisease9thEd,27HumanImmunodeficiencyVirusInfection,AlanJ.Magill, 217247,2013

HIVdiseaseprogressionandtheoccurrenceofselectcomplication

Natural history of untreated HIV infection and relationship of specific opportunistic infections to CD4 count.

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Initialinfectionanddisseminationofhumanimmunodeficiencyvirus(HIV)infection

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,123TheImmunologyofHumanImmunodeficiencyVirusInfection,JohnE.Bennett,15261540.e3,2015

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Directandindirecteffectsofhumanimmunodeficiencyvirus(HIV)infection

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,123TheImmunologyofHumanImmunodeficiencyVirusInfection,JohnE.Bennett,15261540.e3,2015

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AtlasofSexuallyTransmittedDiseasesandAIDS4thEd,14HumanImmunodeficiencyVirusInfectionandtheAcquiredImmunodeficiencySyndrome,StephenA.Morse,240255,2010

MechanismsforCD4+Tcell

killing

Directcellkilling

Indirect

Apoptosis

Immuneattackofuninfected

cells

lHIVinhibitedhematopoiesis

Thymusdamage

Lymphnodedamage

Tcellanergy

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Hunter'sTropicalMedicineandEmergingInfectiousDisease9thEd,27HumanImmunodeficiencyVirusInfection,AlanJ.Magill, 217247,2013

EstimatedPerActRiskforAcquisitionofHIVbyExposureRoute*

ExposureRoute Riskper100exposurestoanHIVinfectedsource

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Bloodtransfusion 90.Needlesharinginjectiondruguse 0.67Percutaneousneedlestick 0.3

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Receptiveanalintercourse 0.5Receptivepenilevaginalintercourse 0.1Insertiveanalintercourse 0.065Insertivepenilevaginalintercourse 0.05Receptiveoralintercourse 0.01Insertiveoralintercourse 0.005

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s Mothertochildtransmission(withoutbreastfeeding) 30Breastfeedingfor18months 15

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Positivepredictiverateofhumanimmunodeficiencyvirus(HIV)confirmatoryassayisafunctionofdiseaseprevalence

Atverylowdiseaseprevalence(0.01%),thepositivepredictivevalueoftestingdeclinessharplywithanyfalsepositivetestresults.Astheprevalenceofinfectionincreases,thepositivepredictivevalueimprovesdespiteafewfalsepositivetestresults.AsHIVscreeningeliminatesthemajorityofHIVnegativeindividualsforfurtherconfirmation,theprevalenceofthepopulationofsamplesreferredforconfirmatoryassayincreasesdramaticallyandwillbeintherangeof90%.Thepositivepredictivevalue forthesequentialstrategyremainshighdespiteanyfalsepositive

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,122DiagnosisofHumanImmunodeficiencyVirusInfection,JohnE.Bennett,15031525.e7,2015

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WHOstagesofHumanImmunodeficiencyVirus(HIV)infection*byCD4+Tlymphocytecountandpercentageoftotal

lymphocytes.

Stage1(HIVInfection) CD4+TLymphocytecountof500cells/LStage2(HIVInfection) CD4+TLymphocytecountof350499cells/LStage3(AdvancedHIVdisease{AHD}) CD4+TLymphocytecountof200349cells/LStage4(AquiredImmunodeficiencySyndrome{AIDs})

CD4+TLymphocytecountof200cells/LorCD4+Tlymphocytepercentageof15

*Forreportingpurposesonly.Amongadultsandchildrenaged5years.Percentageapplicableforstage4only.Amongadultsandadolescents(aged13years).CDCalsoincludesafourthstage.Stageunknown:laboratoryconfirmationofHIVinfectionbutnoinformationonCD4+TLymphocytecountorpercentageandnoinformationonAIDsdefiningconditions.

AtlasofSexuallyTransmittedDiseasesandAIDS4thEd,13HumanImmunodeficiencyVirusInfectionandtheAcquiredImmunodeficiencySyndromeEpidemiology,StephenA.Morse,230239,2010

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AtlasofSexuallyTransmittedDiseasesandAIDS4thEd,14HumanImmunodeficiencyVirusInfectionandtheAcquiredImmunodeficiencySyndrome,StephenA.Morse,240255,2010

HIVRNAsetpointandriskofdiseaseprogression

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AIDSDefiningConditions Bacterialinfections,multipleorrecurrent*

Candidiasisofbronchi,trachea,orlungs

Candidiasis,esophageal

Cervicalcancer,invasive

Coccidioidomycosis,disseminatedorextrapulmonary

Cryptococcosis,extrapulmonary

Cryptosporidiosis,chronicintestinal(>1moduration)

Cytomegalovirusdisease(otherthanliver,spleen,ornodes)

Cytomegalovirusretinitis(withlossofvision)

Encephalopathy,HIVrelated

Herpessimplex,chroniculcer(s)(>1moduration);bronchitis,pneumonitis,oresophagitis

Histoplasmosis,disseminatedorextrapulmonary

Isosporiasis,chronicintestinal(>1moduration)

Kaposisarcoma

Lymphoidinterstitialpneumoniaand/orpulmonarylymphoidhyperplasia*

Lymphoma,Burkitts(orequivalentterm)

Lymphoma,immunoblastic(orequivalentterm)

Lymphoma,primary,ofbrain

MycobacteriumaviumintracellularecomplexorMycobacteriumkansasii,disseminatedorextrapulmonary

Mycobacteriumtuberculosis,anysite(pulmonaryorextrapulmonary)

Mycobacterium,otherspeciesorunidentifiedspecies,disseminatedorextrapulmonary

Pneumocystisjiroveciipneumonia

Pneumonia,recurrent

Progressivemultifocalleukoencephalopathy

Salmonellasepticemia,recurrent

Toxoplasmosisofbrain

WastingsyndromeofHIVinfection

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,121EpidemiologyandPreventionofAIDSandHumanImmunodeficiencyVirusInfection,JohnE.Bennett

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Goldman'sCecilMedicine24thEd,396TreatmentofHumanImmunodeficiencyVirusInfectionandAcquiredImmunodeficiencySyndrome,LeeGoldman,21852196,2012

LikelihoodfordevelopmentofAIDSwithin3years.

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Terapi

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,131ManagementofOpportunisticInfectionsAssociatedwithHPVInfection,JohnE.Bennett,16421665.e5,

Terapi

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,131ManagementofOpportunisticInfectionsAssociatedwithHPVInfection,JohnE.Bennett,16421665.e5,

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Terapi

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,131ManagementofOpportunisticInfectionsAssociatedwithHPVInfection,JohnE.Bennett,16421665.e5,

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Terapi

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,131ManagementofOpportunisticInfectionsAssociatedwithHPVInfection,JohnE.Bennett,16421665.e5,

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ProphylaxistoPreventFirstEpisodeofOpportunisticDisease

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,131ManagementofOpportunisticInfectionsAssociatedwithHPVInfection,JohnE.Bennett,16421665.e5,

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Profilaksis

Goldman'sCecilMedicine24thEd,396TreatmentofHumanImmunodeficiencyVirusInfectionandAcquiredImmunodeficiencySyndrome,LeeGoldman,21852196,2012

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Goldman'sCecilMedicine24thEd,396TreatmentofHumanImmunodeficiencyVirusInfectionandAcquiredImmunodeficiencySyndrome,LeeGoldman,21852196,2012

Opportunisticinfectionprophylaxisandtreatmentinadolescentsandadults

Riskfactor Agent Prophylacticmedication

CD4cellcount

Goldman'sCecilMedicine24thEd,396TreatmentofHumanImmunodeficiencyVirusInfectionandAcquiredImmunodeficiencySyndrome,LeeGoldman,21852196,2012

Opportunisticinfectionprophylaxisandtreatmentinadolescentsandadults

Riskfactor Agent ProphylacticmedicationPPD>5mmindurationorrecentTBcontactmonthbutnoactiveTBandnohistoryoftreatmentforactiveorlatentTB

Mycobacteriumtuberculosis

INHpyridoxinefor9months;ifunlikelytocomplete9courseandonHAART:rifabutinpluspyrizinamidefor2months

Contactwithchickenpoxorshinglesinvaricellazosterseronegativeindividuals

Varicellazoster Varicellazosterimmunoglobulins(VZIG)

HIVinfected Streptococcuspneumoniae PneumovaxMeningococcus foryouthattendingthemilitaryorcollegeandconsiderForunvaccinatedadults

Menactra

Negativeanti HBcandpreviouslyunimmunizedorunderimmunizedtohepatitisB

HepatitisB RecombivaxHBorEnergerixB

Negativeanti hepatitisAserology HepatitisA Havrix

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Profilaksis

Goldman'sCecilMedicine24thEd,396TreatmentofHumanImmunodeficiencyVirusInfectionandAcquiredImmunodeficiencySyndrome,LeeGoldman,21852196,2012

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TopikPembicaraan

Epidemiologi Patofisiologi InfeksiOportunistik ProfilaksisdanTerapi Pencegahan Kesimpulan

PotentialFactorsInfluencingMothertoChildTransmissionofHIVMaternalFactors AdvancedHIVdisease,asmeasuredby:

Clinicalstaging LowCD4+lymphocytecount Higherviralloads p24antigenemia

PrimaryHIVinfection Viralphenotype:syncytiuminducing Viralgenotype:virulentmutantstrainofHIV Coinfectionwithothersexuallytransmitteddiseases Firstborntwins Obstetricevents

Vaginaldelivery Invasiveproceduresorfetalmonitoringduringlabor Prolongedprematureruptureofmembranes(>4hr)

Oldermaternalage Cigarettesmokingandillicitdruguseduringpregnancy Breastfeeding Unprotectedsexualintercoursewithmultiplepartnersweight

LabororBirthCanalFactors

Cervicovaginalviralload

LocalHIVspecificimmuneresponse

Maternalfetaltransfusionofblood

ImmuneFactorsHumoral Neutralizingantibody

Antibodydependentcellularcytotoxicity

gp120V3loopantibody

MHCconcordanceandhomozygosity

MaternalhumanleukocyteantigenA*2301

CellMediated CytotoxicTlymphocytes CD8suppression

Mucosalimmunity OtherFetalorPlacentalFactors Chorioamnionitis Prematurity Lowbirth

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,128HumanImmunodeficiencyVirusInfectioninWomen,JohnE.Bennett,15901615.e8,2015

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AtlasofSexuallyTransmittedDiseasesandAIDS4thEd,14HumanImmunodeficiencyVirusInfectionandtheAcquiredImmunodeficiencySyndrome,StephenA.Morse,240255,2010

RelativesensitivitiesofvariousvirologicalassaysfortheearlydiagnosisofHIV1infectionininfantsfrombirthto6monthsofage

HIV1assay Timetodetection114days 14months 6monthsMeansensitivity(%)*Culture 41 89 91DNAPCR 40 80 97p24antigen 27 40 56ICDp24antigen 32 97 87RNAPCR 32 91 100PCR,polymerasechainreaction;ICD,immunecomplexdissociated.*Dataisbasedonninepublishedstudies.

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FactorsAssociatedwithFertilityDesiresandIntentionsinWomenLivingwithHIVInfection

POSITIVE INFLUENCES NEGATIVE INFLUENCESYounger age Personal health concernsNo children Having had one or more childrenAntiretroviral therapy Concerns about infecting partnerInterventions to preventmothertochild transmission

Concerns about infecting child

Partners/family members wishforchildren

Negative or judgmental attitudes ofhealthcare workers, family, andcommunity

HIVrelated stigma HIVrelated stigmaNewmale partner Fear of disclosure

Mandell,Douglas,andBennett'sPrinciplesandPracticeofInfectiousDiseases8thEd,128HumanImmunodeficiencyVirusInfectioninWomen,JohnE.Bennett,15901615.e8,2015

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Kesimpulan

Deteksidini ARVsedinimungkin MonitorCD4dankemungkinanIO(InfeksiOportunistik) Pencegahan:BerbasisCD4,imunisasi

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