hiv transmission routes, pathology, treatment and prevention · truvada (tenofovir and ftc)...
TRANSCRIPT
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HIVTransmissionRoutes,Pathology,TreatmentandPreventionDamianKellyFeb2017
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HIVTransmissionRoutes• Factorsnecessaryfortransmission
• HIVpresenceinbodyfluids
• Commonroutesoftransmission
• Lesscommonroutesoftransmission
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• HIVpresentininfectiousquantitiesinblood,semenandvaginalfluids,breastmilkofanHIVpositiveperson
• Entersbodythroughsexualorgans,bloodstream,mouth
• Presenceofvirusinbodyfluid
• Quantityofvirusinbodyfluid
• Qualityofvirusinbodyfluid
• Routeintothebody/bloodstream
Quality
Quantity
Routeoftransmission
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CommonRoutesofTransmission
• Unprotectedanalorvaginalsex
• Bloodtobloodcontact– e.g.sharingneedles
• Mothertobaby– duringpregnancy,birthorthroughbreastfeeding
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LessCommonRoutesofTransmission• Oralsexwithoutacondom
• Sharingsextoys
• Needlestickinjuries
• Eyesplashes
• Skinpiercing/tattooing(unsterilised equipment)
• Donatedbloodandtissueincountrieswithinadequatescreening
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WhenshouldyougetanHIV test?Youhavesexwithoutacondom,withotherpeopleotherthanyourpartner– *oral,vaginaloranalsex
Youhaveunprotectedsex(withoutcondomorimpropercondomuse)withyourpartnerwhoinjectsdrugsorhassexwithothers
Youinjectdrugsandshareneedleswithotherpeople
Watch:https://www.youtube.com/watch?v=Kw_e_O6MdM4
Allpregnantwoman
Sexualassault/rape
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HIVTestingAntibodytest
• Antibodytests• Rapidtestsandhometests
• Antibodiesareproducedbytheimmunesystemwhichiswhatthetestlooksfor.Canbeusedinbloodandoralfluid
• 3– 12weeksafterinfectionbeforedetection
• Rapidantibodyscreeningtesttakes30minutes• OraQuick HIVtestswabfromthemouthtakesabout20minutes• Hometestingkitsinvolvesafingerprickbloodsamplecantake7– 10daysforresults
• Allpositivetestresultswillrequireasecondconformationtest
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FourthGenerationTests
• Fourthgenerationtestslookfor• HIVantibodiesandantigens• Antigensareforeignsubstancesthatcauseyourimmunesystemtoactivate• Antigenispartofthevirusandpresentduringacuteinfection• Antigenp24isproducedbeforeantibodiesareproduced
• 2– 6weeksforthebodytomakeenoughantigensandantibodiesforthetesttodetectHIV
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NucleicAcidTest(NAT)
• Nucleicacidtest• Doesnotlookforantigensorantibodies
• Itlooksforthevirus• Givesapositiveornegativeresult• Andtheactualamountofthevirus
Takes7– 28daysforNATtodetectthevirus
Veryexpensiveandrarelyused
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HIVTypes• Type1• 4strainsclassedintofourgroups• M,N,O,P.M(major)groupglobalinfections• WithingroupMatleast9subtypesA-K• Baccountsformostclinicaltrials
• Type2• ConcentratedinWestAfrica
• Lessinfectious• Progressesslower• Fewclinicaltrials• Optimumtreatmentpoorlyunderstood
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HIVlifecycle
https://www.youtube.com/watch?v=fBPicJ-AZAk
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HIVDrugs• ThereareseveralcategoriesofdrugsusedtotreatHIV
• Acombinationofcategoriesshouldbeused• Monotherapy1980’sx• Dualtherapy1980’s– 1990’sx• Tripletherapy1990’sonwards
• Untilrecentlywhendualtherapyandevenmonotherapyarebeinginvestigatedagainwiththenewdrugs.
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WhyStartTreatment?• Topreventinjury/damagetotheimmunesystem
• Torepairdamagedone
• Topreventonwardtransmission
• Toremainhealthy
• Tobeincontrol
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KeyTerms• Viralload• CD4count• Resistancetests• Druglevels• Viraltropism• Renalfunctiontest• Liverfunctiontests• Fullbloodcount
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ViralLoad• Themostimportanttestoncestartedontreatment!
• Showshowmuchvirusisintheblood
• Resultmaylooklike100000copies/mLforsomeonenotonART• ForsomeoneonARTitmaylooklike3copies/mL(undetectable)
• ViralloadsshowiftheARVtherapyisworkingornot
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CD4Count• Thismeasureshowyourimmunesystemisfunctioning-
• AhighCD4countmeansitsgood• AlowCD4countisnot
• Anythingunder250isdangerous• ThemostimportanttestbeforecommencingARVtherapy
• CD4cellsarelymphocytecells(whitebloodcells)sometimeknownasT-cells
• TwotypesofT-cells– CD4arehelpercellsandleadagainstinfectionandCD8cells“suppressor”cells.Thesearealsokillercells
• AnormalCD4countrangewouldbe400– 1600cellspercubicmillimeter
• CD4%isthetotallymphocytes(whitebloodcells)thatareCD4cells
• StartingARVwillincreasetheCD4countastheimmunesystemrecovers
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WhentoStartTreatmentAIDS /symptoms
CD4<200
CD4200- 350
CD4350- 500
CD4>500
USDHHS2016 RECOMMENDED
IAS/USA2016 RECOMMENDED
EACS2016 RECOMMENDED
BHIVA2016 RECOMMENDED
WHO2016 StronglyrecommendedPRIORITY
Stronglyrecommended
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ResistanceTesting• ThisshowsiftheHIVvirusisresistanttoHIVdrugs• Itshowsifthechosendrugwillwork
• Avirusthathasmutatedmaycausedrugresistancetooccur• K103NwillstopEFVandNVPfromworking• M184Vwillstop3TCandFTCworking
• Missingmedicationcancauseresistancetodevelop
• Andetectableviralloadwhileontreatmentcancauseamutationtooccur
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TherapeuticDrugMonitoring• Drugleveltesting
• ThisshouldbedoneoncecommencedonARV
• Detectshowmuchdrugthebodyisabsorbing• ForARV’stoworkproperlytherehastobeasetlevelofdruginthebody
• Sometimesadoseadjustmentmaybeneededorachangeoftherapyifthebodydoesnotabsorbthedrugcorrectly• Manyreasonswhydrugsarenotabsorbed• Adherencelevelisthebiggestreasonwhydruglevelsmaybelow….
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RenalFunctionTests(TX&PrEP)• HIVAssociatedNephropathy(HIVAN)
damagecausedbyHIVtokidneys
• NephrotoxicitytoxicityorinjurytothekidneyssideeffectsofARV’s
• Upto30%ofHIV+peoplehavekidneydisease
• Measuresthelevelsofurea,creatinineandsaltsdipstickurinetestsoftenpickupincreasedproteinlevelswhichindicatepotentialkidney
damage
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DrugClasses• Fixeddosecombination(STR)singletabletregime
• Nukes;nucleosideornucleotidereversetranscriptaseinhibitors(NRTIs)
• Non-nucleosidereversetranscriptaseinhibitors(NNRTIs)
• Integraseinhibitors(INIs)
• CCR5Inhibitors(entryinhibitor)
• ProteaseInhibitor(PIs)
• PK(pharmacokinetic)booster
• AttachmentInhibitor
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Fixed Dose Combination (STR) single tablet regime
NAME Restrictions and recommended dose
Ammount of Tablets
Atripla Efavirenz 600mg + emtricitabine 200mg +Tenofovir DF 300mg
Take at night and not with high fat meal
1 tablet a day
Eviplera Rilpivirine 25mg + emtricitabine 200mg + Tenofovir DF 300mg
Take with food 1 tablet a day
Odefsey Rilpivirine 25mg + emtricitabine 200mg + TAF 25mg
With food 1 tablet a day
Triumeq Dolutegravir 50mg + Abacavir 600mg + lamivudine 300mg
With or without food 1 tablet
Genvoya Elvitegravir 150mg + cobicistat 150mg + emtricitabine 200mg + TAF 10mg
Take with food 1 tablet a day
Stirbald Elvitegravir 150mg + cobicistat 150mg + emtricitabine 200mg + Tenofovir DF 300mg
Take with food 1 tablet a day
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Nukes;nucleosideornucleotidereversetranscriptinhibitors(NRTIs)
SingleNukes
lamivudine(3TC)
1x300mgor2x
150mgtakenasonce
dailyortwicedaily
dose
1if300mg
2if150mg
Abacavir
(Ziagen,Epzicom
2x300mgtablets
takenasoncedailyor
twicedailydose
2Tablets
Emtricitabine(FTC)
(Emtriva)
1x200mgonceaday 1Tabletaday
TenofovirDF
(Viread)
1X300MGtabletonce
aday
1Tabletaday
Zidovudine(AZT) 1x250mgtwicedaily 2tablets
ddi
(Videx,Didanosine)
1tabletadayeither;
125,200,250or
400mg)takeonempty
stomach2hrsbefore
eating
1tabletaday
DualNukes
Truvada(Tenofovirand
FTC)
TenofovirDF300mg+
emtricitabine200mg
1Tabletaday
Descovy(TAF) TAF25mg+
Emtricitabine200mg
1tabletaday
Kivexa(Abacavirand
3tc)
Abacavir600mg+
lamivudine300mg
1Tabletaday
Combivir(AZTand3T) Onetablettwiceaday 2Tabletsaday
TripleNukes
Trizivir
(AZT+3TC+abacavir)
Onetablettwiceaday 2tabletsaday
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Non-nucleosidereversetranscriptaseinhibitors(NNRTI’s)
Efavirenz Notwithhighfatmeal.1x600mgtabletor3x200mgtabletsatnight
1Tabletor3tabletsdependingondose
Nevirapine200mg(Viramune)Nevirapine400mg(Viramunepr)
200mgoncedailyforfirst14days.Then1x200mgtablettwiceadayor2x200mgonceadayOR1x400mgprolongedreleasetabletonceaday
1or2Tabletsdependingwhether200mg0r400mg
Etravirine (Intelence)
1x200mgtablettwiceadaytakewithfood
2Tabletsaday
Rilpivirine(Edurant)
1x25mgtabletonceadaywith500kcal)
1Tabletaday
NottobeusedtotreatHIVtype2infections
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Integraseinhibitors(INIs)
Raltegravir(Isentress)
1x400mgtablettwiceadaywithorwithoutfood
2Tabletsaday
Elvitegravir(Vitekta)
1x85mgtabletonceaday(or1x50mgtablettwiceadayifdrugresistance)Withorwithoutfood
1Tabletaday
Dolutegravir(Ticicay) 1x50mgtabletonceadayor1x50mgtwiceadayifdrugresistanceWithorwithoutfood
1or2Tabletsaday
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EntryInhibitor(CCR5inhibitors)
Maraviroc 150mg300mgor600mgasdirectedanddependingonwhichotherdrugsareused
1or2or4tabletsaday
T20(Fuzeon,enfuvirtide)
90mginjectionundertheskintwiceaday
2injectionsaday
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ProteaseInhibitors(PIs)
Atazanavir(Reyataz)
1x300mgtablet+aboosteronceadaywithfood.150mgand200mgarealsoavailable
1Tabletplusabooster
Darunavir(Prezista)
1x800mgplusboosteronceadayor1x600mgplus100mgboostertwiceadayifresistance.Takewithfood
1or2tablets(basedondose)plusboosters
Atazanavir/cobicistat(Evotaz)
Takewithfood 1tabletaday
Darunavir/cobicistat(Prezcobix)
Takewithfood 1tabletaday
Lopinavir(Kaletra)200/50or100/25mg
2x200/50mgtwicedailyOR4x100/25mgwithorwithoutfood
4TablestusingthelargerdoseOR8Tabletsusingthesmallerdose
Foasamrenavir(Telzir)
1x700mg+100mgRitonavirtwiceadayTakewithorwithoutfood
2Tabletsadayplusbooster
Saquinavir(Invirase)
2x500mgtwiceadayTakewithfood
4tabletsadayplusbooster
Tripranavir(Aptivus)
2x250mgtwiceadaytakewithfood
4Tabletsadayplusbooster
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Pharmacokineticboosters(PK)
Cobicistat(Tybost)
150mgtabletonceadayusedetoboostAtazanavir,DarunavirandElvitegravir
Dependsonboosteddrug
Ritonavir(RTV)Norvir
100mgtabletsusedatdifferentdoses
DependsonPIdrugs
WarningofDrugDrugInteractionsespeciallyEcstasyandViagra
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WhattoStartNRTI NNRTI PI INS
USDHHS2016 TAF/FTCTDF/FTCABC/3TC
DRV/r DTGEVGRAL
IAS2016 TAF/FTCABC/3TC
DTGEVGRAL
EACS TAF/FTCTDF/FTCABC/3TC
RPV DRV/r or/c DTGEVGRAL
BHIVA2016 TAF/FTCTDF/FTC
RPV ATV/rDRV/r
DTGEVGRAL
WHO2015 TDF+3TCorFTC EFV
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ARTin2017• 29approveddrugs• 5broadmechanisticclassesNRTI,NNRTI,PI,INI’s,entryinhibitor
• 10recommendedfirstlinechoices• 1standardstrategy:2NRTI’s+1NNRTIorPIorINSTI
• Properties• virologic activity• safetyandtolerability• convenience• Accessandcost• Lifeexpectancy
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Undetectable – Whatdoesitmean?Undetectablemeanshavingaviralloadbelow50copies.
Undetectable doesNOT meancuredofHIV.HIVinfectionisstillpresentwithinthebodybutcannotbepickeduponastandardHIVtest.
Undetectable meansthevirushasbeen“switchedoff”andisnolongerreplicatingathighlevelswithinthebody.
Undetectable meanstheriskofonwardtransmissionisvirtually0%chanceoftransmittingthevirus.
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Adherence
• Whatisadherence?
• Howmuchisenough?
• Howcanadherencebeimproved?
• Whataboutmissedorforgottentablets?
Andsoto….
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PreExposureProphylaxis
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PrEPPreExposureProphylaxis
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PrEPISNOTNEW….
“The reduction in mother-to-child transmission of humanimmunodeficiency virus (HIV) is regarded as one of the mosteffective public health initiatives.
In the absence of treatment, the risk of vertical transmission of HIV is as high as 25-30%. With the implementation of HIV testing, counseling, antiretroviral medication,delivery by cesarean section prior to onset of labor, and discouraging breastfeeding, themother-to-infant transmission has decreased to less than 2%”
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PrEPPreExposureProphylaxis
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Oct2009:RV144HIVvaccine
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July2010:Tenofovirmicrobicide
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Oct2013:Firstrectalmicrobicidetrial• MTN017:• PhaseIItrial• Reducedglycerineformulationoftenofovirgel
• Daily• Beforeandaftersex
• Truvadaoraldaily• Enrolling186MSM/TSWinPeru,SouthAfrica,ThailandandtheUnitedStates
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Howaretheantiretrovirals used? • Oralpill• Topicalgel(microbicide)
•Rectal•Vaginal
• Injection• Intravaginalring
Howoftenaretheantiretroviralsused? • Daily• Intermittently• Coitally(before/sex)
Howmanyantiretroviralsareused? • Single• Combination
Whatantiretroviralsareused? • MostlyTRUVADA• Over25available
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Adherence
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PrEPPreExposureProphylaxis
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PrEPPreExposureProphylaxis
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PrEPPreExposureProphylaxis
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PrEPPreExposureProphylaxis
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Adherence
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Adherence
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Adherence
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Adherence
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Adherence
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