Evidenceforinterventionstostrengthenthe

HIVpreventioncascade:asystematicreviewofreviews

ShariKrishnaratne etal.

CENTREFOREVALUATION

Improvingglobalhealthpracticethroughevaluation

WhyisHIVpreventionimportant?

• PreventionGapReport(UNAIDS,2016):Effortstoreachfewerthan500000newHIVinfectionsby2020areofftrack• Hugesuccessesintreatmentuptake• DeclineofnewHIVinfectionsissubstantiallyslowerthanthefallinAIDS-relateddeaths,andepidemiccontrolremainsoutofreach• In2015,theestimatednumberofnewHIVinfectionsinadults(1·9millionworldwide)wasnofewerthanin2010.

• AccelerateddeclineinnewHIVinfectionsisrequiredtoavoidareboundoftheepidemic,especiallyamongkeypopulations

Outline

• Introduction• HIVpreventioncascade:aformalised framework• Landscapeofpreventioninterventions

IncidenceDeterminantsframeworks• Whatpathogen?Where?• ModesoftransmissionOutbreak

• R=b.C.d• Transmission,Contact,DurationModelling

• CorepopulationstoMARPStokeypops• Generalised,concentrated,mixed,low-levelRiskStrata

• SocialCognitiveModels• Norms,Self-efficacy,Attitude,SkillsBehaviour

• Gender,Inequality• Globalisation,PoliticalEconomySocialTheory

• Proximatedeterminants,SocialEpi,SocialDrivers• Socio-ecological,StructuraldeterminantsMultilevelframeworks

PreventionInterventiontypologies• Growinglistoftechnologies• Condoms,PrEP,TasP etcBiomedical

• Differentsettings(schools,healthcentres)• Differentmodes(counselling,didactic,participatory)Behavioural

• SocialDeterminantsofBehaviour• Ecological/environmental/policylevelStructural

• Biomedical,Behavioural,Structural• Oftenmanifestsasalistofbiomedicaltools

CombinationPrevention

• Programmes• CriticalEnablers• DevelopmentSynergies

InvestmentFramework

Discussion

• Needformulti-level,multi-pathwayframeworks• But currentframeworksmaybetoodescriptive,complex,notattunedtothenewpreventionenvironment

• Needformulti-sectoral,combinationprevention• But artificialseparationofbiomedical,behaviouralandstructuralhasledtothembeingweakonhowpopulationimpactonincidencecanbeachieved• Biomedical:underestimatetechnology-impactgap• Behavioural:evidenceconfusesefficacyandeffectiveness• Structural:overlapwithbehavioural,weakontheoryofchange

• Absenceofanintegratedframeworklinkingneed,preventioninterventionsandastrategyforpopulation-levelimpact

Cascades

• PMTCT• HIVcare• HIVprevention?• Facility-levelorpopulation-leveldata• Cross-sectionalorlongitudinal• Representsoneinterventionatatimebutdoesnotimplytheyshouldbeusedinisolation• E.g TasP,condoms,VMMC,PrEP,sexualpartnernumbers

Limitations

• ApplytoHIVacquisitiononly,nottransmission• Quantifydirectprotectiononly• Donotshowcombinedprotectionofmorethanonepreventionintervention• Basedonpopulation-at-risk,whichcanonlybeinferredfromepidemioloigcal data

Preventionevidence• TherehasbeenrecentprogressinbiomedicalHIVpreventioninterventions- malecircumcision,pre-exposureprophylaxis,andearlyinitiationofwidespreadantiretroviraltherapy(‘testandtreat’)• Fewevaluationsofthesebiomedicalinterventionsonapopulationlevelexist• Therearealsofewlarge-scaleevaluationsofbehaviouralandstructuralHIVpreventioninterventions• Theobjectiveofthisresearchistoconsolidatetheavailableevidenceontheeffectivenessofbiomedical,structuralandbehaviouralHIVpreventioninterventions

ReviewMethods

• ConductedasynthesisoftheevidenceonHIVpreventioninterventionsinLMICsoverthepasttwentyyears.• EvidencefromasystematicreviewofreviewsofHIVpreventioninterventions.• Threeindependentsearchesforreviewsonbiomedical,structural,andbehaviouralinterventionsforHIVprevention.• SearchedPubmed/MEDLINE,OVID,ISIWebofKnowledge/Science,theCochraneLibraryofSystematicReviews,clinicaltrials.gov,andhealth-evidence.org usingspecificsearchterms.• Includedreviewsthatwerepublishedafter1995.• ExtractedprimarystudiesfromthereviewsiftheyassessedatleastoneofHIVincidence,HIVprevalence,reportedcondomuse,anduptakeofHIVtesting,andwereimplementedinanLMIC(structural/behaviouralonly).

HIVpreventioncascade

• Demandfor• Supplyof• Adherenceto• Productefficacy

Byappropriatepopulation

Directmechanisms• Interventionsinclude:malecircumcision,PrEP,microbicides,condoms• Thereisgoodevidencethatbiomedicalinterventionsworkattheindividuallevel• Moststudiesofbiomedicalpreventionproductsfocusonefficacy(includingmanyRCTs)• Example:malecircumcisiontoreduceriskofHIVinfectioninheterosexualmen

• StrongevidenceofadecreasedriskofHIVacquisition- pooledresultsfromRCTsandobservationalstudiesdemonstratearelativeriskreductionof~54%(Perera etal;Millsetal;Byakika-Tusiime etal;Kriegeretal;Leietal)

• Example:oralPReP• Evidencefromfourtrialsdemonstratedefficaciesof44-75%indifferentpopulations

(iPrEx trial,Bangkoktrial,TDF2trial,andthePartnersPrEP study)(Okwundu etal;Jiangetel)

Supplyinterventions• Interventionsinclude:condomdistribution,cleanneedle/syringeexchangeprogrammes,communitymobilization• EvidencefrominterventionsthatincreasesupplyofHIVpreventionservices• Example:masscondomdistribution• Strongandconsistentevidencethatsuchprogrammeshavepositiveeffectsonreportedcondomuse(Charania etal;Fossetal;Shamanesh etal)

• SomeevidencetosuggestreductionsHIVprevalenceandincidence

Demand-focused

• Interventionsinclude:peer-basedapproaches,information,education,andcommunicationapproaches• Oftentargetedatkeypopulations,youngpeople,contextspecific• Example:Empowermentforfemalesexworkers

• Moderateevidence(RCTsandobservationalstudies)ofconsistenteffectivenessatincreasinguptakeofHIVtesting (Kerriganetal[2013;2015];Cherisch etal;Tanetal;Wariki etal)

• Strongevidenceofagenerallypositive,butnotconsistenteffectoncondomuse• Mixedpositive/inconsistentreductionsinHIVincidenceandprevalence

Use-focused

• Interventionsinclude:counselling-basedapproaches,socialdeterminantsofhealthapproaches• Example:SouthAfricaprogrammewhichfocusedonpeoplenotlivingwithHIVanddelivereda60-minuteriskreductioncounsellingsessionledbyhealtheducatoranddeliveredwithinahealthcaresetting.• Example:InterventioninSouthAfricaconsistedofpatient-centered discussionsbetweencounsellorsandpatientslivingwithHIVduringregularclinicalvisitsfocusedonHIVriskreductionandtailoredtospecificpatientneeds.• Example:CashtransfersinMalawifocusedonkeepingyounggirlsinschool

Assessmentofstrengthofevidence

DirectMechanisms

Demandsideinterventions

Supply-sideinterventions

Adherence/useinterventions

Discussion

• EvidencefromseveralstudiesusingrandomizedtrialdesignsinsupportoftheefficacyofdirectmechanismstopreventHIV.• Evidencetosuggestthatsupplysideinterventionsthatincreaseaccesstotheseefficacioustechnologiescanbeeffective• Demand,supplyanduseinterventionsareallcriticaltoincreasinguptakeofandadherencetodirectmechanismstopreventHIV.• Interventionsandcombinationofinterventionsrequiredtotranslatetheefficacyofdirectmechanismsintopopulation-levelimpactwillrequiremonitoringthesedomainstounderstandgapsandsupportinterventiondevelopment.

Conclusions

• Wehavepreventiontoolsthatworkattheindividuallevel,and thegoalofensuringpopulationlevelimpactofthesetoolsisachievable• UseofanHIVpreventioncascadethatincludesthesedomainsprovidesaframeworktounderstandwhyaprovendirectmechanismisfailingtohaveapopulation-levelimpactandsupportsthedevelopmentandimplementationofinterventionstotargetthesedomains.• Systematicreviewswhichexplorethecurrentevidenceinlinewiththecascadeshouldbeconductedinordertofullyunderstand‘whatworks,’forwhom,andunderwhichcircumstances.