HIV Prevention in Clinical Care Settings2014 Recommendations of the International Antiviral ...

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ClinicalReview&Education
SpecialCommunication
HIV Prevention in Clinical Care Settings
2014 Recommendations of the International Antiviral Society–
USA Panel
JeanneM.Marrazzo,MD,MPH;CarlosdelRio,MD;DavidR.Holtgrave,PhD;MyronS.Cohen,MD;
SethC.Kalichman,PhD;KennethH.Mayer,MD;JulioS.G.Montaner,MD;DarrellP.Wheeler,PhD,MPH;
RobertM.Grant,MD,MPH;BeatrizGrinsztejn,MD,PhD;N.Kumarasamy,MD,PhD;StevenShoptaw,PhD;
RochelleP.Walensky,MD,MPH;FrancoisDabis,MD,PhD;JeremySugarman,MD,MPH;ConstanceA.Benson,MD
Editorialpage349
IMPORTANCEEmergingdatawarranttheintegrationofbiomedicalandbehavioral
Supplementalcontentat
recommendationsforhumanimmunodeficiencyvirus(HIV)preventioninclinicalcare jama.com
settings.
CMEQuizat
jamanetworkcme.comand
OBJECTIVE ToprovidecurrentrecommendationsforthepreventionofHIVinfectioninadults
CMEQuestionspage430
andadolescentsforintegrationinclinicalcaresettings.
DATASOURCES,STUDYSELECTION,ANDDATASYNTHESIS Datapublishedorpresentedas
abstractsatscientificconferences(past17years)weresystematicallysearchedandreviewed
bytheInternationalAntiviral(formerlyAIDS)Society—USAHIVPreventionRecommenda-
tionsPanel.Panelmemberssuppliedadditionalrelevantpublications,reviewedavailable
data,andformedrecommendationsbyfull-panelconsensus.
RESULTS TestingforHIVisrecommendedatleastonceforalladultsandadolescents,with
repeatedtestingforthoseatincreasedriskofacquiringHIV.Cliniciansshouldbealerttothe
possibilityofacuteHIVinfectionandpromptlypursuediagnostictestingifsuspected.At
diagnosisofHIV,allindividualsshouldbelinkedtocarefortimelyinitiationofantiretroviral
therapy(ART).Supportforadherenceandretentionincare,individualizedriskassessment
andcounseling,assistancewithpartnernotification,andperiodicscreeningforcommon
sexuallytransmittedinfections(STIs)isrecommendedforHIV-infectedindividualsaspartof
care.InHIV-uninfectedpatients,thosepersonsathighriskofHIVinfectionshouldbe
prioritizedfordeliveryofinterventionssuchaspreexposureprophylaxisandindividualized
counselingonriskreduction.Dailyemtricitabine/tenofovirdisoproxilfumarateis
recommendedaspreexposureprophylaxisforpersonsathighriskforHIVbasedon
backgroundincidenceorrecentdiagnosisofincidentSTIs,useofinjectiondrugsorshared
needles,orrecentuseofnonoccupationalpostexposureprophylaxis;ongoinguseof
preexposureprophylaxisshouldbeguidedbyregularriskassessment.Forpersonswhoinject
drugs,harmreductionservicesshouldbeprovided(needleandsyringeexchangeprograms,
supervisedinjection,andavailablemedicallyassistedtherapies,includingopioidagonistsand
antagonists);low-thresholddetoxificationanddrugcessationprogramsshouldbemade
available.Postexposureprophylaxisisrecommendedforallpersonswhohavesustaineda
mucosalorparenteralexposuretoHIVfromaknowninfectedsourceandshouldbeinitiated
assoonaspossible.
CONCLUSIONSANDRELEVANCE Datasupporttheintegrationofbiomedicalandbehavioral
approachesforpreventionofHIVinfectioninclinicalcaresettings.Aconcertedeffortto
implementcombinationstrategiesforHIVpreventionisneededtorealizethegoalofan
AIDS-freegeneration.
AuthorAffiliations:Author
affiliationsarelistedattheendofthis
article.
CorrespondingAuthor:JeanneM.
Marrazzo,MD,MPH,Box359932,
HarborviewMedicalCenter,
3259thAve,Seattle,WA98104
JAMA.2014;312(4):390-409.doi:10.1001/jama.2014.7999 ([email protected]).
390 jama.com
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CombinationHIVPreventioninClinicalSettings SpecialCommunication ClinicalReview&Education
T
heavailabilityofcombinationantiretroviraltherapy(ART) PanelrecommendationswerelimitedtoHIVpreventionfor
haschangedthelivesofmillionsofindividualslivingwith clinicalcaresettingsfornonpregnantadultsandadolescents.
humanimmunodeficiencyvirus(HIV),transformingHIV RecommendationsforpreventionincludedARTthatwasavail-
fromafatalinfectiontoamanageablechronicdisease.Incidenceof able(approvedbyregulatorybodiesorinexpandedaccess[com-
newHIV-1infectionsworldwidehasdecreasedbyanestimated33% passionateuse])orinlate-stagedevelopment(newdrugapplica-
since2001butremainshighatapproximately2.3millionnewin- tionfiled).Recommendationsweremadebyfull-panelconsensus
fectionsin2012.IntheUnitedStates,approximately50000new andratedaccordingtostrengthoftherecommendationandqual-
infectionsoccureachyear—anumberthathasremainedlargelyun- ityofsupportingdata(Table1andBox1).4Ratingswereprovided
changedsincethe1990s.1 onlyforrecommendationssupportedbyclinicalorobservational
Theintegrationofbiomedicalandbehavioralapproachesto studydata.Thepaneldevelopedtheserecommendationsregard-
HIVprevention,coupledwithARTforthoseinfected,represents lessofclinicalsetting;thus,theyarerelevanttotheglobalcom-
thecornerstoneofeffortstocurbthespreadofHIVinfection.2In munity.However,mostofthecost-effectivenessliteraturecitedis
anefforttoprovidepracticingclinicians,publichealthexperts, specifictotheUnitedStatesandotherwell-resourcedsettings,
andpolicymakerswithaframeworktoimplementthebestHIV suchasCanada,WesternEurope,andAustralia.Totheextentthat
preventioninterventions,theInternationalAntiviralSociety—USA resourceutilization,carestructures,andARTcostsvarywidely
(IAS—USA)Panelhasdevelopedrecommendationsthatintegrate acrossdifferentsettings,theeconomicdiscussionsshouldbe
biomedicalandbehavioralpreventioninthecareofpeopleliving interpretedaccordingly.
withoratriskforHIVinfection.Theserecommendationsare
intendedasbestpracticebasedonavailableevidence.Imple-
mentingtheserecommendationsmaypresentstructural,eco-
SectionA.HIVTestingandKnowledge
nomic,orpoliticalchallenges.However,benefitstobederived
fromtheirimplementationshouldcontributesubstantiallytopre- ofSerostatus
ventingdiseaseprogression,promotinghealthylifeyearsgained,
Self-knowledgeofHIVserostatusisthepivotalstepindirectingin-
andpreventingnewHIVinfections.
terventionstopreventHIVinfection,enablinglinkageofnewly
Informulatingtheserecommendations,thepanelintention-
diagnosedpersonstocareaswellasprovisionofpreventioninter-
allyavoideddistinguishingbetweenbehavioralandbiomedicalin-
ventionstothosefoundtobeHIV-seronegativebutatriskofinfec-
terventions,choosingtoemphasizethatprovidingpreventionin
tion.Despitetheimportanceofthisknowledge,approximately50%
care—forpeoplelivingwithoratriskforHIVinfection—requiresa
ofpeoplelivingwithHIVworldwide—and16%ofthoseintheUnited
combinationofactivities.
States—donotknowtheirserostatus.5Moreover,HIV-infectedper-
sonswhoareunawareoftheirserostatusmayaccountforasmuch
as45%ofnewHIVinfectionsintheUnitedStates.6Inaddition,per-
Methods sonswhoreceiveapositiveHIVtestresultoftenreducetheirHIV-
relatedriskbehaviors.6-8
AsystematicliteraturereviewusingMedlineandEMBASEwas
In2006,theUSCentersforDiseaseControlandPrevention
conductedtoidentifyrelevantpublisheddata.Specificsearch
(CDC)issuedguidelinesrecommendingroutineopt-outHIV
termsandlimitsaredetailedinthesupplementalsectiononthe
processofrecommendationdevelopment(eMethodsinthe
Supplement).Approximately250relatedmanuscriptswere
Table1.StrengthofRecommendationandQualityofEvidenceRating
selectedbasedonscientificevidenceormajorguidelines.Panel Scalea
membersalsoconductedhandsearchesfornewlypublished
Category/Grade Definition
reportsandabstractsfromscientificconferencesthroughoutthe
Strengthofrecommendation
process.Datanotpublishedorpresentedinapeer-reviewedset-
A Strongsupport
tingwerenotconsidered.
B Moderatesupport
RecommendationsweredevelopedbytheInternationalAnti-
C Limitedsupport
viralSociety–USAHIVPreventionRecommendationsPanel,an
Qualityofevidence
internationalpanelofexpertsinHIVbiomedicalandbehavioral
Ia Evidencefrom1ormorerandomizedcontrolledclinical
scienceandpractice.ThepanelconvenedinpersoninMarch2013
trialspublishedinthepeer-reviewedliterature
andmetregularlybyteleconferencethereafter.Panelmembers
Ib Evidencefrom1ormorerandomizedcontrolledclinical
serveinavolunteer(nofinancialcompensation)capacityanddo trialspresentedinabstractformatpeer-reviewed
scientificmeetings
notparticipateinindustrypromotionalactivitiessuchasspeaker
IIa Evidencefromnonrandomizedclinicaltrialsorcohortor
bureaus,industry-paidlectures,orothermarketingactivitiesdur- case-controlstudiespublishedinthepeer-reviewed
ingpanelmembership(detailsavailableintheeMethodsinthe literature
Supplement).Teamsevaluatedevidenceandsummarizedpanel IIb Evidencefromnonrandomizedclinicaltrialsorcohortor
case-controlstudiespresentedinabstractformatpeer-
discussionsforeachsection.Priortoconvening,members reviewedscientificmeetings
declaredanddiscussedpotentialconflictsofinterestandrecused III Recommendationbasedonthepanel’sanalysisofthe
accumulatedavailableevidence
themselvesfromservingassectionleadersorteammembers
accordingly.Adescriptionofthepanelprocessisincludedinthe aAdaptedinpartfromtheCanadianTaskForceonthePeriodicHealth
Examination.4
eMethodsintheSupplement.
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ClinicalReview&Education SpecialCommunication CombinationHIVPreventioninClinicalSettings
Box1.RecommendationsforIntegratedBiomedicalandBehavioralApproachestoHIVPrevention
A.HIVTestingandKnowledgeofSerostatus NeedleExchangeandOtherHarm-ReductionInterventions
AlladultsandadolescentsshouldbeofferedHIVtestingatleastonce. AmongPeopleWhoInjectDrugs
Rating:AIII SimultaneousaccesstoART,needleandsyringeexchangeprograms,su-
Todirecttheneedforadditionaltesting,cliniciansshouldperiodically pervisedinjectionsites,medicalizedheroin,andmedicallyassistedtherapy
assessHIV-relatedrisks,includingsexualanddrug-useactivities,inall (whichincludesopioid-substitutiontherapy)shouldbeprovidedtoHIV-
adultsandadolescents. infectedpeoplewhoinjectdrugs.Rating:AIaforeachelement;AIIIfor
thecombination
Personsathigherrisk(thoseengaginginriskbehaviorsorresidingin
areasofortestingatvenueswithhighseroprevalence)shouldbetested Forindividualswhousesubstancesinwaysotherthaninjection,ARTwith
morefrequently,atintervalsappropriatetotheindividual’ssituation. adherencesupportandbehavioralcounselingshouldbeprovided.Rat-
ing:AIIa
AllpersonsshouldbeinformedpriortoundergoingHIVtesting;how-
ever,pretestcounselingshouldbesufficientonlytomeettheindividu-
C.Individual-andStructural-LevelInterventionstoPromoteMovement
al’sneedsandtocomplywithlocalregulations.Therighttorefusetest-
ofHIV-InfectedPersonsThroughtheContinuumofHIVCare:
ingmustbehonored,butcliniciansshouldensurethatrefusalsare
AdditionalConsiderations
informeddecisions.Rating:AIII
LinkagetoHIVcareforHIV-infectedindividualsisanessentialcompo-
Asthecircumstanceswarrantanddependingonthetestused,at-riskper-
nentofexpandedHIVtestingandshouldbeactivelyfacilitatedassoon
sonswhotestHIV-seronegativeshouldreceiveinformationaboutthepos-
aspossiblefollowinganewdiagnosisofHIV.Rating:AIa
sibilityofafalse-negativetestresultduringthewindowperiodpriorto
appearanceofdetectableantibodyandshouldbeencouragedtoobtain Strengths-basedcasemanagementinterventionsinwhichpatientsiden-
repeattestingatanappropriatetime.Rating:AIIa tifyandusepersonalstrengthsshouldbeusedtofacilitatelinkagetoand
retentioninHIVcare(examplesavailableathttp://effectiveinterventions
Approachtotesting
.org/en/HighImpactPrevention/PublicHealthStrategies/ARTAS.aspx).Rat-
Testswiththebestperformance(sensitivity/specificity)shouldbeused. ing:AIa
Rating:AIIa
Additionalpatientsupportservicesarerecommended,includingpa-
Rapidtestingshouldbeprioritizedforpersonslesslikelytoreturnfor tienthealthnavigation,communityandpeeroutreach,provisionofcul-
theirresults.Rating:AIIa turallyappropriateprintmedia,verbalmessagespromotinghealthcare
Couplestestingshouldbeaccommodatedandencouraged.Rating:AIa utilizationandretentionfromclinicstaff,andyouth-focusedcaseman-
agementandsupport.Rating:AIIa
Self-testingandhometestingshouldbeconsideredforthosewhohave
recurrentrisk,difficultieswithtestinginclinicalsettings,orboth.Rat-
ing:BIII D.PreventionMeasuresAimedatHIV-UninfectedIndividuals
RiskAssessmentandRiskReductionforHIVInfection
B.PreventionMeasuresSpecifictoHIV-InfectedIndividuals Aspecificriskassessmentcoveringrecentmonthsshouldbeconducted
AntiretroviralTherapy todeterminethesexualandsubstanceusepracticesthatshouldbethe
focusofriskreductioncounselingandappropriateriskreductionser-
Cliniciansshouldprovideeducationaboutthepersonalhealthbenefits
vicesshouldbeoffered.Rating:AIa
ofARTandthepublicbenefitsofpreventionoftransmissionandshould
assesspatients’readinesstoinitiateandadheretolong-termART.Rat- ForpeopleathighriskforHIVinfectionwhotestHIV-seronegative,risk-
ing:AIII reductioninterventionsorservicesarewarranted,especiallyforindi-
vidualsandcoupleswhoseekrepeatHIVtestingtomonitorseroconver-
ARTshouldbeofferedondetectionofHIVinfection.Rating:A1a
sion.RatingAIa
Strategiesforadherencesupportshouldbeimplementedandtailored
toindividualpatientneedsorthesetting.Rating:AIa PreexposureProphylaxis
CliniciansshouldbealerttothenonspecificpresentationofacuteHIVin- DailyFTC/TDFaspreexposureprophylaxisshouldbeofferedto
fectionandurgentlypursuespecificdiagnostictesting(plasmaHIVviral PersonsathighriskforHIVbasedonbackgroundincidence(>2%)or
load)ifthisissuspected.Rating:AIIa recentdiagnosisofincidentsexuallytransmittedinfections,espe-
ciallysyphilis,gonorrhea,orchlamydia.Rating:AIa
CounselingonRiskReduction,DisclosureofHIVSerostatus,
andPartnerNotification Individualswhohaveusedpostexposureprophylaxismorethantwice
inthepastyear.Rating:AIIa
Regularassessmentofsexualandsubstanceusepracticesshouldbeper-
formedinHIV-infectedpersonstodirectindividualizedrisk-reduction Peoplewhoinjectdrugsandwhoshareinjectionequipment,inject1
counseling,whichshouldbedeliveredincombinationwithscreeningfor ormoretimesaday,orinjectcocaineormethamphetamines.Rating:
sexuallytransmittedinfection,condomprovision,andharmreductionser- AIa
vices(discussedbelow)forpeoplewhoinjectdrugs,andintegratedwith Preexposureprophylaxisshouldbepartofanintegratedrisk-reduction
strategiestomaintainadherence.Rating:AIII strategy,soitsusemaybecomeunnecessaryifaperson’sbehavior
Assistanceshouldbeprovidedforpatient-orclinician-basednotifica- changed.Thus,cliniciansshouldregularlyassesstheirpatients’riskand
tionofsexandinjectiondrugusepartnerstofacilitatethepatient’stest- considerdiscontinuingpreexposureprophylaxisifthesexualandpart-
ingandlinkagetocareaswellaseffortstodiscloseHIVinfectiontorel- neringpracticesorinjectiondrugusebehaviorsthatinvolvedexposure
evantpartnersandotherkeypersons.Rating:AIII toHIVchange.Rating:AIII
(continued)
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CombinationHIVPreventioninClinicalSettings SpecialCommunication ClinicalReview&Education
Box1.RecommendationsforCombinationHIVPrevention(continued)
HIV-infectedpersonsshouldbeaskedabouttheHIVserostatusoftheir Voluntarymedicalmalecircumcisionshouldbediscussedwithmenwho
sexualpartners,andpreexposureprophylaxisshouldbediscussedifthey havesexwithmenandwhoengageinprimarilyinsertiveanalsex,par-
haveregularcontactwithHIV-uninfectedpartners.PartnerswhoseHIV ticularlyinsettingsofhighHIVprevalence.Rating:BIIb
serostatusisunknownshouldundergocounselingandtesting.Consid- Parentsandguardiansshouldbeinformedofthepreventivebenefitsof
erationsshouldincludewhethertheinfectedpartner’sviralloadissup- maleinfantcircumcision.3Rating:BIIb
pressedonART,accesstocarefortheuninfectedpartner,andcoverage
ofassociatedcosts.Rating:AIIb
E.PreventionIssuesRelevanttoAllPersonsWithoratRisk
HIVtestingshouldbeperformedbeforestartingpreexposureprophy- forHIV-1Infection
laxis,ideallywithasensitive,combinationantigen-antibodyassayca-
ScreeningandTreatmentforSexuallyTransmittedInfections
pableofdetectingacuteorearlyinfection(afourth-generationassay),
Routine,periodicscreeningforcommonsexuallytransmittedinfections
andregularly(monthlytoquarterlydependingonindividualrisk)there-
atanatomicalsitesbasedonsexualhistoryshouldbeperformed(Box2).
after.Screeningforclinicalsymptomsthatmaysignalacuteinfection
Rating:BIIa
shouldbeperformed.InsuspectedcasesofacuteHIVinfection,plasma
HIVviralloadshouldbedeterminedimmediatelyandpreexposurepro- HIV-infectedpersonsshouldbetestedforhepatitisCvirusatentrytocare
phylaxisshouldbedeferreduntilacuteinfectionisruledout.Rating:AIa andassessedatregularintervalsforrelatedrisks,includinghigher-risk
sexualpractices.Rating:BIIa
PersonstobegivenTDF-basedpreexposureprophylaxisshouldhavea
creatinineclearancerateofatleast60mL/min.Dataarenotavailableto Quadrivalenthumanpapillomavirusvaccinationshouldbeofferedtoall
informarecommendationforpreexposureprophylaxisforpersonswith HIV-infectedpersonswhofulfilltheAdvisoryCommitteeforImmuniza-
acreatinineclearancerateoflessthan60mL/min.Rating:AIa tionPracticescriteriaforitsadministration.Rating:AIIa
ImmunitytohepatitisBvirusshouldbeensuredforallpersonsinitiating ImmunitytohepatitisBvirusshouldbeensuredforallHIV-infectedper-
TDF-basedpreexposureprophylaxis.RatingAIIa sonsincarewhohavenotalreadybeeninfectedwithhepatitisBvirus.
RatingAIIa
PostexposureProphylaxis
RoutinescreeningforHSV-2infectionshouldbeconsideredforHIV-
Postexposureprophylaxisshouldbeofferedtoallpersonswhohavesus-
infectedpersonswhodonotknowtheirHSV-2serostatusandwishto
tainedamucosalorparenteralexposuretoHIVfromaknowninfected
considersuppressiveantiviraltherapytopreventtransmissionofHSV-2.
sourceasurgentlyaspossibleand,atmost,within72hoursafterexpo-
Rating:CIa
sure.Rating:AIIb
ThepostexposureprophylaxisregimenshouldconsistoftheUSPublic ReproductiveHealthCare:HormonalContraception
HealthService–preferredregimen,whichiscurrentlyFTC/TDFandralte- Currentdataarenotsufficientlyconclusivetorestrictuseofanyhor-
gravir.Rating:BIIb monalcontraceptionmethod,andwomenusingprogestin-onlyinject-
ablecontraceptionshouldbeadvisedtoalsoalwaysusecondomsand
Womenwhoreceivepostexposureprophylaxisshouldbeofferedemer-
otherHIV-preventivemeasuresasfeasible.Intheinterim,HIV-infected
gencycontraceptiontopreventpregnancy.Rating:BIIb
womenshouldbecounseledwithregardtotheavailabilityofarangeof
Personswhoreceivepostexposureprophylaxisshouldberescreenedwith optionsforfamilyplanning,includinghormonalcontraception.Rating:
afourth-generationHIVantigenandantibodytest3monthsaftercomple- BIIa
tionoftheregimen.Rating:BIIb
Abbreviations:ART,antiretroviraltherapy;FTC/TDF,emtricitabine/tenofovir
VoluntaryMedicalMaleCircumcision disoproxilfumarate;HIV,humanimmunodeficiencyvirus;HSV-2,herpessimplex
Voluntarymedicalmalecircumcisionshouldberecommendedtosexu- virustype2.
allyactiveheterosexualmalesforthepurposeofHIVprevention,espe-
ciallyinareaswithhighbackgroundHIVprevalence.Rating:AIa
testinginhealthcaresettings9;despitethis,manymissedoppor- diagnosistoapproximately15to20days,thusallowingdiagnosis
tunitiesfortestinginclinicalcarecontinuetooccur.In2013,theUS ofpersonswhoareoftenhighlyinfectious.14Newdiagnosticalgo-
PreventiveServicesTaskForcerecommendedroutineHIVscreen- rithmsalsoomittheneedforroutineconfirmatoryWesternblot
ingforallpersonsaged15to65years.10Bothoftheseguidelinesnote testing.15TheCDCSexuallyTransmittedDiseaseTreatmentGuide-
thatwhereprevalenceofundiagnosedHIVinfectionis0.1%orless, linesrecommendthatmenwhohavesexwithmen(MSM)whohave
routinescreeningmaybesupplantedbyscreeningonthebasisof multipleoranonymouspartners,havesexinconjunctionwithillicit
riskassessment. druguse,usemethamphetamine,orwhohavesexpartnerswhopar-
NewdevelopmentssuchasHIVrapidtests,fourth-generation ticipateintheseactivitiesbescreenedforsexuallytransmittedin-
antibodyandantigenassays(eTableintheSupplement),11fewerle- fections(STIs)andHIVmorefrequently(every3to6months)than
galbarrierstotesting,andintegrationofscreeningindiverseset- MSMwithoutsuchriskfactors.16
tingsshouldfacilitateincreasesinHIVtestingandearlydiagnosis, Forcoupleswhoareorplantobesexuallyactive,HIVtestingis
timelyreceiptofresults,andbetterlinkagetocare.12Home-andcom- aneffectiveinterventionforbothheterosexualandsame-sex
munity-basedtestingstrategies,includingself-testing,areespe- couples.17,18WithcouplesHIVtesting,participantsreceivetesting
ciallyimportantforpopulationswithunmethealthcareneeds.13 andcounselingtogether;individualslearnnotonlyoftheirownHIV
Fourth-generationassaysallowclinicianstodetectsomeacuteand serostatusbutalsothatoftheirpartner(s),whichfacilitatesthede-
recentHIVinfection,narrowingthewindowbetweeninfectionand liveryoftailoredpreventionmessagesandcareplans.
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ClinicalReview&Education SpecialCommunication CombinationHIVPreventioninClinicalSettings
CounselingassociatedwithHIVtestingisacomplextopic.In ThePresident’sEmergencyPlanforAIDSRelief69andthe
theUnitedStates,statelawsvaryastowhatisrequired.19Ata WorldHealthOrganization(WHO)70nowrecommendthatHIV-
minimum,individualsshouldknowthattheyarebeingtested. infectedpersonswhosesexpartnersareHIV-uninfectedbe
Somestudieshavefoundthatcounselingconductedatthetime offeredimmediateinitiationofART,irrespectiveofCD4cellcount.
ofHIVtestingservestoreduceHIV-relatedriskbehaviorsand TheInternationAntiviralSociety–USA71andUSDepartmentof
subsequentSTIs;however,somestudiesdidnotdemonstrate HealthandHumanServices72recommendthatARTinitiationbe
theseeffects.20-31Counselingshouldnotbeanimpedimentto offeredtopersonswithHIVinfection,regardlessofCD4cell
HIVtesting.Indeed,currentguidancefromtheCDCstatesthat count,forbothindividualhealthandtransmissionpreventionben-
preventioncounselingshouldnotberequiredwithHIVdiagnostic efits.Mostrecently,theWHOhasrecommendedthatARTbe
testingoraspartofHIVscreeningprogramsinhealthcare offeredtoallpersonswithCD4cellcountslessthan500/μL
settings.9Last,theeconomicvalueofHIVscreeningiswellsub- regardlessofsymptomsandwithCD4cellcountsgreaterthan
stantiatedandisenhancedwhentransmissionpreventionben- 500/μLinanumberofspecificclinicalsettings.70Extrapolating
efitsassociatedwithscreeningareincluded.32-34 fromobservedindividualandpopulationbenefits,studieshave
Briefriskassessmentandbriefclinicallyfeasibleriskreduc- demonstratedthatintheUnitedStates,expandedscreening
tionservicesmaybeconsideredforpersonsathighriskofHIV (1timeinlow-riskandannuallyinhigh-riskpersons,suchasthose
infection,includingthosewithanincidentSTI,evidenceofinjec- inserodiscordantpartnershipsorwithmultiplesexpartners)with
tiondruguse,orwhoreportsexualordrugusingrisk.Inthesec- immediateARTinitiationforindividualswhotestHIV-seropositive
tionsbelow,wediscusstheseservicesbothforpersonsliving isacost-effectivemethodofpreventingtransmission.73EarlyART
withHIVandforpersonsatincreasedriskforHIVinfection(see targetedtoHIV-serodiscordantcoupleshasalsobeenprojectedto
Table2and3). becost-effectiveinresource-limitedsettings.74
ForrecommendationsregardingHIVtestingandknowledgeof RecentecologicalanalysesfromareaswhereMSMaremost
HIVstatus,seeBox1. affectedbyHIVinfectionhavenotreporteddeclinesinHIVinci-
denceorprevalenceasARTusehasexpanded,despitethe
encouragingdatafromthePARTNERstudy.63,75SustainedHIV
transmissionfromuntreated(orinconsistentlytreated)MSMwith
SectionB.PreventionMeasuresSpecific
highlevelsofplasmaandgenitalHIVRNAislikelydrivingthese
toHIV-InfectedIndividuals
epidemics.75-77
AntiretroviralTherapy AcuteandearlyHIVinfectionmaylimittheeffectofARTon
SuppressionofinfectiousHIV-1inbloodandgenitalsecretions thepreventionofHIVtransmission.Duringthisperiod,plasma
throughprovisionofARTishighlyeffectiveinreducing—indeed, andgenitalviralloadsreachhighconcentrationsandmayremain
largelyeliminating—theriskofongoingHIVtransmission.Observa- elevatedforseveralmonths.Veryfewpeoplelearntheirserosta-
tionalstudiesofheterosexualcoupleshaveconfirmedthatsuccess- tusduringthisperiod.78NewerHIVtests12andtestingalgorithms
fulARTreducesprobabilityofHIVtransmission.58,59In11of13such thatincorporateHIV-1RNAtestingmayenhancethelikelihoodof
studies,almostnoHIVtransmissionwasobservedwhenthein- detectionduringthistime,buttheoveralleffectislikelytobe
fectedpartnerwasreceivingART.60,61Instudiesinwhichtransmis- smallbecausetheclinicaldiagnosisofacuteHIVinfectionisfre-
sioneventsoccurreddespiteART,theHIV-infectedparticipantswere quentlynotsuspected.79Becausepeoplewithacuteandearly
likelynotreliablyadherenttoART.62ThePARTNERstudy,apro- HIVinfectioncontributedisproportionatelytothespreadof
spectiveobservationalstudyof767serodiscordantcouples,40% HIV,80,81correctdiagnosisandpromptinterventionareneeded.7
ofwhichweresame-sexmalecouples,recentlyreportednoHIV SmallstudiesofthesexualbehaviorofpeoplewithearlyHIV
transmissionoccurringduringanestimated894couple-yearsofob- infectiondonotsuggestthatbehaviorchangealonewillsuffice;
servationduringwhichthemajorityofpenetrativeanalorvaginal thus,immediate,lifelongARTisrecommended.82Earlytreatment
sexwascondomless,andwheretheHIV-infectedpartnerwasre- preservesCD4cellcounts83andreducesongoingviraldiversifica-
ceivingART.63 tionandthesizeoftheviralreservoir.84,85Moreover,failureto
TheHPTN052(HIVPreventionTrialsNetwork052)study64was provideARTduringaclinicalencounterthatoccursearlyinthe
arandomizedclinicaltrial(RCT)undertakentoprospectivelydeter- diseasecanresultinlosstofollow-upwiththepatient,whomay
minethepreventionbenefitofART.Among1763HIVserodiscor- re-engagewithcareonlywhentheyhavedevelopedanHIV-
dantcouplesin9countries,HIVtransmissionwasreducedbymore relatedcomplication.86
than96%duringaperiodof18monthsbyaddingARTtostandard AdherencetoARTiscrucialforsustainedHIV-1suppression.Con-
preventionstrategies.Theresultsalsodemonstratedaclinicalben- sistentwiththecurrentInternationalAssociationofPhysiciansin
efit(reductioninincidenttuberculosis)toindividualsofferedART AIDSCareguidelines,once-daily,fixed-dosecombinationARTispre-
atCD4cellcountsgreaterthan350/μLcomparedwithARTinitia- ferredwheneverpossible.71,72,87Evenwithsuchregimens,com-
tionatCD4cellcountslessthan250/μL.65Anecologicalstudyamong pleteadherencecanbechallenging.Behavioralinterventions88that
peoplewhoinjectdrugsinVancouver,BritishColumbia,Canada,sug- haveshownpromiseincludebriefpsychosocialcounseling,suchas
gestedthatARTsignificantlyreducesspreadofHIVinfection.66In cognitivebehavioraltherapy,89-93risk-reductionbehavioral
Kwazulu-Natal,SouthAfrica,forevery1%increaseinARTuse,a1.4% interventions,40motivationalinterviewing,93-95managedproblem-
decreaseinHIVincidencewasobserved.67Anassociationofsimi- solvingcounseling,96adverse-effectscopinginterventions,97peer-
larmagnitudewasestablishedinapopulation-basedanalysisinBrit- ledsocialsupportgroups,98,99andcounselinginterventionsforspe-
ishColumbia.66,68 cificpopulations,includingrecentlyreleasedinmates,100youth,101
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CombinationHIVPreventioninClinicalSettings SpecialCommunication ClinicalReview&Education
Table2.CentersforDiseaseControlBestandGoodLevelsofEvidenceforPreventionInterventionsforPersonsLivingWithHIV/AIDSa
Levelof
Evidence
InterventionName Design Sample DurationandStudyPeriod MajorOutcomes perCDCb
CLEAR(adaptedfrom Community-based,individual- 175YoungPLWHat Eighteenweekly2-h 20-Percentage-pointincreasein Best
TeensLinkedto levelinterventionRCT(telephone riskofsubstance sessions(1999-2002) protectedsexactswith
Care)35,36 vsin-personvsdelayeddelivery) abuse seronegativeparnersand13-
with15-mofollow-up percentage-pointincreasein
overallprotectedsexacts(in-
persondelivery)
Eban37 Couple-basedinterventionRCT 535AfricanAmerican Eightweekly2-hsessions 63%Consistentcondomusein Best
withgroupandsingle-couple serodiscordant (2003-2007) interventiongroupcompared
sessionswith12-mofollow-up couples(1070 with48%incontrolgroup
individuals)
HealthyLiving Community-based,individual- 936PLWHconsidered Fifteen90-minsessions 36%Reductioninriskacts Best
Project38 levelinterventionRCTwith5-, atriskoftransmitting (2000-2002) betweeninterventionand
10-,15-,20-,and25-mo controlgroupsat20-mo
follow-up follow-up
Healthy Skill-based,small-group 332PLWH Five2-h,twice-weekly 17Percentagepointshigherin Best
Relationships39 interventionRCTwith3-and sessions(1997-1998) condomuseforvaginalandanal
6-mofollow-up sexactsininterventiongroup
thanincontrolgroupat6-mo
follow-up
IntheMix40 Individualandgroup-level 436PLWH One45-minindividual 66%Fewerunprotectedsexacts Best
interventionRCTwith3-,6-,and session,52-hgroup ininterventiongroupthanin
9-mofollow-up sessions,160-min controlgroupat6-mo
individualsessionover5 follow-upc
wk(2005-2009)
LIFT41 Group-levelinterventionRCT 247PLWHwith Fifteenweekly90-min Copinggroupreduced Best
(copinggroupvssupportgroup) historyofchildhood sessions(2002-2004) unprotectedsexactsbyan
with4-,8-,and12-mofollow-up sexualabuse averageof54%at12-mo
follow-upcomparedwith
supportgroup
PositiveChoice: Computerizedindividual-level 476PLWH Onecomputer-based 15%Fewerunprotectedsexacts Best
InteractiveVideo interventionRCTwith3-and session(2003-2006) ininterventiongroupthanin
Doctor42 6-mofollow-up controlgroupat6-mofollow-up
SeropositiveUrban Group-levelintervention 811HIV-seropositive Six3-h,weeklysessions 5%Fewerparticipantsreported Best
Men’sIntervention (standardinterventionvs MSM (enhanced),11.5-to2-h unprotectedactsofreceptive
Trial(SUMIT)43 enhancedintervention)RCTwith session(standard) analsexinenhancedgroupthan
3-and6-mofollow-up (2000-2002) instandardgroupat3-mo
follow-up
TreatmentAdvocacy Individual-levelprimary 313HIV-seropositive Four60-to90-mine 20%Transmissionriskin Best
Program(TAP)44 care–basedinterventionRCTwith MSM sessionsover8wk,3-mo interventiongroupat6-and
6-and12-mofollow-up check-incall,215-to 12-mofollow-upcomparedwith
90-minfollow-up 23%-25%incontrolgroup
sessionsat6and12mo
(2004-2006)
WiLLOW45 Group-levelinterventionRCT 366Sexuallyactive Four4-h,weeklysessions 44%Reductioninmeannumber Best
with6-and12-mofollow-up HIV-seropositive (1997-2000) ofunprotectedvaginalsexacts
adultwomen (past30d)ininterventiongroup
comparedwithcontrolgroupat
12-mofollow-up
Options/Opciones Individual-levelintervention 497PLWH One5-to10-minsession 79%Decreaseinaveragenumber Good
Project46 randomizedtostudygroups repeatedateachclinic ofunprotectedsexactsin
(interventionvsstandardofcare) visitfor18mo interventiongroupoverthe
with18-mofollow-upperiod (2000-2003) 18-moperioda
Partnershipfor Individual-levelintervention 585Sexuallyactive One3-to5-minsession 38%Decreaseinunprotectedsex Good
Health47 randomizedtostudygroups PLWH repeatedateachclinic actsamongPLWHwith2ormore
(gain-framevsloss-framevs visit(1999-2000) partnersinloss-framegroupat
attention-control)with7-mo follow-up
follow-upperiod
SafeTalk48 Individual-levelinterventionRCT 490PLWH Four40-to60-min 66%Reductioninunprotected Good
with4-,8-,and12-mofollow-up monthlysessions sexactsininterventiongroupat
(2006-2009) 12-mofollow-up,compared
with30%reductionincontrol
groupa
TogetherLearning Group-levelintervention 310HIV-seropositive Twenty-three2-hsessions 82%Fewerunprotectedsexacts Good
Choices(TLC)49 controlledtrialwith9-and adolescentandyoung deliveredover23-mo ininterventiongroupthanin
15-mofollow-up adultclinicpatients period(1994-1996) controlgroup
Abbreviations:CDC,CentersforDiseaseControlandPrevention;CLEAR, reductioninterventionsforPLWHprovidesadditionaldetailedinformationon
ChoosingLife:Empowerment,Actions,Results!;HIV,humanimmuno- evidence-basedandpromisingstudiesintheUnitedStates.51
deficiencyvirus;LIFT,Livelihoods&FoodSecurityTechnicalAssistance; bTheCDCevaluationoftheseinterventionsisadynamicprocess;current
MSM,menwhohavesexwithmen;PLWH,peoplelivingwithHIV/AIDS;RCT, informationisavailableathttp://www.cdc.gov/hiv/dhap/prb/prs/index.html;
randomizedclinicaltrial;WiLLOW,WomenInvolvedinLifeLearningfrom http://www.effectiveinterventions.org/en/Home.aspx.
OtherWomen.
cPercentagereductioncalculatedfromdatapresentedinreference.
aAdaptedfromCDC,2013.50Arecentlypublishedsystematicreviewofrisk
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Table3.BriefBehavioralInterventionsforHIV-UninfectedPersons
Levelof
Intervention Evidenceper
Name Design Sample DurationandStudyPeriod MajorOutcomes CDCa
Focusonthe Individual-level 266Youngadult,African One45-to50-minsession Interventiongrouplesslikelyto Best
Future52 interventionRCT American,heterosexual (2004-2006) experiencereinfectionthancontrol
(motivational men group(31.9%vs50.4%),morelikelyto
interviewing,skill- haveusedcondomsinmostrecent
building,condom intercoursethancontrolgroup(72.4%vs
information)with3- 53.9%),andreportedfewersexual
and6-mofollow-up partnersthancontrolgroup(2.06vs
4.15)
Personalized Individual-level 248MSM One1-hsession(with Reductioninparticipantsreporting Best
CognitiveRisk- counseling optionaldiary)(1997-2000) unprotectedsexwithnonprimary
Reduction interventionRCTwith partners(66%baseline,21%at6-mo
Counseling29 6-and12-mo follow-up,26%at12-mofollow-up)
follow-up
Sister-to-Sister: Individual-levelskill- 564AfricanAmerican One20-minsession 70%ofinterventiongroupreported Best
One-on-One buildingintervention women (1993-1996) practicingprotectedsexat12-mo
SkillsBuilding53 RCTwith3-,6-,and follow-upvs62%ofcontrolgroup
12-mofollow-up
Jamesetal54 Individual-level 492Adultsattendingan One20-minsession(1991) Interventiongroupmorelikelythan NAb
counseling(skills STIclinicintheUnited controlgroupstocarrycondomsifthey
training)intervention Kingdom thoughtsexwithanewpartnerwaslikely
3-groupRCTwith4- (71%vs63%and49%)
and18-mofollow-up
MujerSegura55 Individual-level 924HIV-negativefemale One35-minsession 40%DeclineinSTIincidencein NAb
counseling sexworkersinMexico interventiongroup,27.4percentage
interventionRCTwith pointincreaseincondomusein
didacticcontrolgroup interventiongroupcomparedwith17.5
with6-mofollow-up percentagepointincreaseincontrol
group
SafeintheCity56 Individual-levelvideo 38635Adultsattending One23-minsession 4.9%IncidenceofSTIsinintervention Best
interventioncontrolled 1of3STIclinics (2003-2005) groupvs5.7%incontrolgroupat14
trialrandomizedby .8-mofollow-up
location/timewith14
.8-moaverage
follow-up
SaferSex57 Individual-level 123Adolescentgirlswith One30-minorlonger 60%ofinterventiongroupreported Good
interventionRCTwith anSTI session(includinga7-min protectedsexatlastsexualencounterat
1-,3-,6-,and12-mo video)withboostersessions 12-mofollow-upvs53%ofcontrol
follow-up atfollow-upappointments group
(1996-1999)
Abbreviations:CDC,CentersforDiseaseControlandPrevention;NA,not informationisavailableathttp://www.cdc.gov/hiv/dhap/prb/prs/index.html;
applicable;RCT,randomizedclinicaltrial;STI,sexuallytransmittedinfection. http://www.effectiveinterventions.org/en/Home.aspx.
aTheCDCevaluationoftheseinterventionsisdynamicprocess;current bTheCDCratingsonlevelofevidenceareassignedforUS-basedstudiesonly.
urban-dwellingHIV-seropositiveindividualswithdepression,102and AlthoughimplementationofuniversalARTforHIV-infectedper-
personswithlowhealthliteracyskills.103,104Personalizedtele- sonsremainsincomplete,expandeduseofARTatallstagesofHIV
phonecallsareeffective,andcomputer-administeredadherencepro- infectionhaschangedthedynamicbetweenriskbehaviorsandhow
motionhasshownpromise.105-107Amongpeoplewhoinjectdrugs, theyareperceived.TheeffectofARTonsexualbehaviorislikelycom-
medication-assistedtherapyanddirectlyadministeredARThaveim- plexanddependsonnumerousfactorsattheindividuallevel.51On-
provedadherence.108,109Forrecommendationsregardingthepre- goingbehavioralriskassessmentisacriticalcomponentofcarefor
ventivebenefitsofART,seeBox1. personswithHIVandshouldinformadiscussionofriskreduction.
However,dataindicatethatdespiteevidenceofbenefit,only61%
RiskReduction,DisclosureofHIVSerostatus, ofpeoplelivingwithHIVwhoengageinriskbehaviorwithserodis-
andPartnerNotification cordantpartnersreceiverisk-reductionpreventionservices.117Ef-
Behavioralinterventionshavebeenshowntoreducesexualriskbe- fectivebehavioralrisk-reductionstrategiesaretypicallydelivered
haviors,increasecondomuse,andreducesubsequentSTIsamong usingindividualizedcounselingtechniques,includingmotivational
personslivingwithHIV(Table3).35-51,110-116TheCDChasidentified interviewing118,119andskills-basedcounseling.120,121Insettingswhere
effective,evidence-basedbehavioralrisk-reductioninterventionsde- suchcounselingcannotbedelivered,cliniciansshouldatminimum
velopedforpeoplelivingwithHIV(Table2).50AsseeninTable3, conductabriefriskassessment122,123andreferpatientstoavail-
someofthe“best”and“good”evidence(aslabeledbytheCDC)were ablerelevanthealthservices.Riskscreeningprotocols124maybeuse-
developedbeforeARTwaswidelyavailable.Asubsetofthesein- fultoidentifyindividualsinneedofmoreintensivecounselinginbusy
terventionshasbeensubjectedtoeconomicevaluationandshown clinicalsettings125ortomonitorforincidentSTIs126orclinicalindi-
tobecost-effective.115,116Further,someoftheinterventionsde- cationsofinjectiondruguse.Importantly,risksidentifiedduringthese
scribedinTable2arebriefandcouldbeprovidedinaclinicalset- conversationsshouldfacilitatediscussionaboutpotentialeffectsof
ting,whereasothersaremoreintensiveandwouldlikelybeavail- ongoingriskbehavior,eveninthesettingofsuccessfullysup-
ableonlythroughotherresources. pressedplasmaHIVviralload.Forexample,inflammationcausedby
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genitalSTIsorotherinflammatoryprocessescanincreaseHIV-1RNA inNewYorkCitywhensyringeexchangewaslegalwerecompared
levelsingenitalsecretionsevenwhenplasmaHIVissuppressedby withthoseamongpeoplewhoinjectdrugslivinginNewark,New
ART,thusrenderingthe“fullysuppressed”personpotentially Jersey,whenexchangewasillegal.Peoplewhoinjectdrugslivingin
infectious.127Inaddition,superinfection(acquisitionofasecondHIV NewarkhadsubstantiallyhigherprevalenceratesofHIV,hepatitis
strainafteranimmuneresponsetotheinitialstrainhasbeenestab- Cvirus,andhepatitisBvirusinfectionsandmorefrequentself-
lished)mayberelativelyfrequentinsomepopulationsandmaybe reportedneedlereuseandsharing.144Accesstoasupervisedinjec-
associatedwithpoorclinicaloutcomes.128Last,treatmentforHIV tion facility is associated with improved individual health
doesnotaffecttheriskforacquisitionofotherSTIs.129 outcomes,145-147riskbehaviors,148,149andsocietaloutcomes.150
PersonswithHIVshouldreceiveguidanceandsupportindis- Moreover,theuseofmedicalizedheroininasupervisedinjectionfa-
closinginfectionstatustosexanddruginjectionpartners.Insome cilityhasclinicalbenefit151andiscost-effective.152
jurisdictions,legislationthatcriminalizesHIVexposuremaydiscour- Incontrast,althoughmostpersonswhousedrugstakethem
ageHIV-infectedpersonsfromdisclosure;thus,itisimportantto bymouth,insufflation,smoking,oranalorvaginalinsertionrather
knowtherelevantlegalcontextandtobeawareofresourcesthat thaninjection,datathatmightinformHIVpreventionstrategiestar-
mayfacilitatethisprocess.130Somecaresettingshaveformalized getedatsuchnoninjectiondrugusearelimited.ApproachestoHIV
HIVpartnermanagementprogramsanddemonstratedenhanced preventionforsubstanceusersareconsistentwiththoseusedamong
effectivenessofpartnerelicitationandnotification.131,132Ifself- non–substanceusersandshouldemphasizepreventionofsexual
disclosureisused,factorstodiscussarehowtopreparefordisclo- transmission.Emergingdatasupportnovelstrategies,including
sure,towhomitwillbemade,whenandhowitwilltakeplace,how medicationstotreatstimulantdependenceinMSM153andreduce
itcanaffecttheclientandpersonstowhomdisclosureismade,and riskbehaviorsinactivestimulantusers.154Forrecommendationsre-
thestressfulnatureoftheprocess.133 gardingpreventioninpeoplewhoinjectdrugs,seeBox1.
Forrecommendationsregardingriskreductioncounseling,sta-
tusdisclosure,andpartnernotification,seeBox1.
NeedleExchangeandOtherHarmReductionInterventions SectionC.Individual-andStructural-Level
AmongPeopleWhoInjectDrugs InterventionstoPromoteMovement
Simultaneousscale-upofcombiningaccesstoART,opioidsubsti- ofHIV-InfectedPersonsThroughtheContinuum
tutiontherapy,andharmreductionservicescangreatlyreducethe
ofHIVCare:AdditionalConsiderations
incidenceofHIVinfectionamongpeoplewhoinjectdrugs,andissup-
portedbytechnicalguidelinesfromtheWHO,UnitedNationsOf- TheHIVcarecontinuumprovidesarepresentationofthestepsnec-
ficeonDrugsandCrime,andtheJointUnitedNationsProgramme essarytotakeHIV-infectedpersonsfromdiagnosistosuppression
onHIV/AIDS.134-136InanecologicalstudyinVancouver,BritishCo- ofplasmaHIV-1viralload.Thevalueofinvestinginlinkagetocare
lumbia,Canada,increasedARTcoveragecorrespondedwithreduc- afteranewHIVdiagnosishasbeendemonstrated.155,156Amodel-
tionin“communitymedianplasmaviral”loadandanapproxi- basedstudydemonstratedthatinvestmentsalongthemostdistal
mately50%reductioninnewHIVdiagnoses,includingthoseamong partofthecarecontinuum(ensuringadherence,linkage,andre-
peoplewhoinjectdrugs.66Morerecently,apopulation-basedanaly- tention)weremoreeconomicallyefficientthanthosedevotedtoin-
sisinBritishColumbiademonstratedagreaterthan90%province- creaseHIVscreening.157
widedeclineinnewdiagnosesofHIVinfection,whichwaslargely MovingindividualsacrosstheHIVcarecontinuumcanbeardu-
attributedtotheexpansionofharm-reductionprogramscoupled ousforthoseonthemarginsofthehealthcaredeliverysystem.158,159
withenhancedARTcoverageamongpeoplewhoinjectdrugs.68Un- Interventionsthatconsidertheindividual’ssocialenvironmentand
fortunately,peoplewhousedrugsfacewidespreadbarrierstoac- attendantstructuralfactorsproducemorepositiveandsustain-
cessingARTinmanysettings.137 ableoutcomescomparedwiththosethatdonot.160Commonlycited
Treatmentforopiateaddictionwithopioidsubstitutionthera- communityorstructuralbarriersincludefearofbeingstigmatized
pies,especiallymethadone,increasesthelikelihoodthatpeoplewho becauseofanHIVdiagnosis;joblessnessresultingfromdisclosure;
injectdrugswillinitiateART.138Onceinitiated,methadonemainte- inabilitytoaffordhealthcare;homelessnessorunstablehousing;in-
nanceincreasesARTadherence,includingamonghomeless carceration;lackofasupportivesocialnetwork;foodinsecurity;and
persons.139OpioidsubstitutiontherapieslikelyreduceHIVtrans- legal,legislative,andpolicyfactorsthatposeobstaclestoaddress-
missionbyreducingillicitopioiduse,sharingofinjectionequip- ingtheseconcerns.161,162
ment,numbersofsexpartners,andexchangeofsexfordrugsor Forthesereasons,structuralandcommunity-levelinterven-
money.140Inaddition,thereisnoevidenceofincreasedsexualrisk tions(broadlydefinedasthosethatbuildontheawarenessthaten-
behaviorafterinitiatingARTamongpeoplewhoinjectdrugs.141,142 vironmental,social,political,andeconomicfactorsarepotential
Ofnote,useofopioidsubstitutiontherapiesshouldbevoluntary; sourcesofHIVriskandvulnerability)areincreasinglyimportant.162
coercivetreatmentdoesnotpreventHIVtransmissionanddoesnot
treataddiction.143 LinkagetoCare
Needleandsyringeexchangeprogramslinkindividualstohealth TheperiodafterapersonisinitiallydiagnosedwithHIVrepresents
careservicesandprovidesterileinjectionequipmentandsupplies, acriticalopportunitytoestablishlinkagetocare.Failuretodosore-
reducingassociatedtransmissionrisks.NoRCTsdocumenteffi- ducestheopportunitytoaddresscurrenthealthissues,accesspre-
cacyfortheseprograms,althoughobservationalreportssupport ventiveservices,andinitiatetimelyART.However,datatoinform
theiruse.Healthoutcomesamongpeoplewhoinjectdrugsliving interventionstoensurethatthislinkageismadearesparse.OneRCT
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Table4.CompletedClinicalTrialsofImmediateAntiretroviralTherapyforHIV-PositivePartnersandMedical
MaleCircumcision
Protective
Sample Effect,%
Study Size Population Design HIVIncidence (95%CI)
AntiretroviraltherapyforHIV+partner
HPTN05265 1763 HIV-serodiscordant ImmediateARTvs ImmediateART:0.1/100 96(73to99)
couples(heterosexual deferredART py;control:1.7/100py
andsamesex)
Medicalmalecircumcision
ANRS 3274 HIV-seronegativemen Circumcisionvsno ImmediateART:0.85 60(32to76)
1265175 circumcision /100py;control:2.1
/100py
Rakai176 4996 HIV-seronegativemen Circumcisionvsno ImmediateART:0.66 51(16to72)
circumcision /100py;control:1.33 Abbreviations:ART,antiretroviral
/100py
therapy;HIV,human
Kisumu177 2784 HIV-seronegativemen Circumcisionvsno ImmediateART:2.1/100 53(22to72) immunodeficiencyvirus;HPTN,HIV
circumcision py;control4.2/100py
PreventionTrialsNetwork.
evaluatedabrief(upto5sessions)casemanagementintervention RiskAssessmentandRiskReductionforHIVInfection
focusedonidentifyingindividualstrengths,reducingbarrierstoob- Thereisstrongevidencethatbriefbehavioralcounselingdelivered
tainingcare,andaccompanyingpersonstoappointments.Com- topersonsatriskforHIVinfectionreducessexualriskbehaviors,
paredwithpassivereferral,theinterventionwasmoreeffectivein increasescondomuse,andreducessubsequentSTIsincluding
creatinglinkagetocare.163Useofoutreachefforts,financialincen- HIV.50,110-114,184-188TheEXPLOREStudy,amulticity,randomized
tives,navigationassistance,partnerservices,andsocialmarketing trialofa10-sessioncounselinginterventionamongMSM,demon-
havesuccessfullyengagedindividualsfromunderservedandmar- strateda39%reductioninHIVincidenceduringa12-to18-month
ginalizedpopulations,includingpersonsofcolorandMSM.164-166Fur- periodaftercounselingandan18%reductioninincidenceduringa
therresearchisneededtoidentifybarrierstocareandoptimalstrat- 48-monthperiod.189,190Thesefindingsarebolsteredbyameta-
egiesforincreasinglinkagetocare.Newapproachestoprogram analysisofrandomizedtrialsthattestedmuchbriefer,single-
scienceshouldinformthisprocessandareespeciallyimportantin sessionsexualriskreductioncounselinginterventionsthat
resource-limitedsettings. embodiedsimilarprinciplesofbehaviorchange.191Reductions
inincidentSTIshavebeendemonstratedtoresultfrombrief
RetentioninCare interventionsofskills-basedindividualizedcounselingintrials
Consistentretentionincarehasbeenassociatedwithshortertime withhigh-riskmenandwomen,andanumberhavebeenlabeled
toviralloadsuppression,lowercumulativeviralloadburden, as “best” or “good” evidence-based interventions by CDC
improvedimmunefunction,decreasedmortality,anddecreased (Table3).29,50,52-57Notsurprisingly,interventionsthatinvolveda
engagementinHIVtransmissionbehaviors.167,168Alargeobserva- longerdurationofasinglecounselingsessionweremoreeffective
tionalstudyfoundthatretentionincreasedsubstantiallyafterthe thanthoseofbrieferduration.Face-to-facecounselinginterven-
implementationofclinic-wideinterventions,includingprint tionsalsohadgreatereffectsthanmedia-deliveredmessages.Risk
remindersandbriefverbalmessagesusedbyallclinicstaff.169 reductioncounselingcanbedeliveredaloneorideallyincombina-
Patientnavigationinterventions,communityandpeeroutreach, tion with biomedical prevention strategies targeting HIV-
printmedia,verbalmessagesfromclinicstaff,financialincentives, uninfectedpersons.6,50,192,193
andyouth-focusedcasemanagementandsupporthavebeen Themosteffectiveindividualizedcounselingprovidespa-
associatedwithincreasedretentionincare.107,170-173ForHIV- tientswithself-managementskillsandcondoms.110,194,195Inaddi-
infected,opioid-dependentindividuals,1RCTdemonstratedthat tion,contentanalysesofeffectivecounselinghaveidentifiedcom-
medication-assisteddrugtreatment(buprenorphineandnaloxone) monprinciplesthatpromotepreventivebehaviors:fosteringasense
wasassociatedwithincreasedretentionincare.174Forrecommen- ofself-beliefandself-worth,distinguishingfactfrommyth,evalu-
dationsregardingclinic-wideinterventions,seeBox1. atingoptionsandconsequences,formulatingcommitmentto
change,planningskills,promotingself-control,establishingplea-
surablealternativestohigh-risksexualactivity,negotiatingsaferbe-
haviors, setting limits, and acting to help others protect
SectionD.PreventionMeasuresAimed
themselves.196Althoughvariouscounselingapproacheshavenu-
atHIV-UninfectedIndividuals
ancestailoredtoparticularpopulationsandservicesettings,most
Untilrecently,thepreventionofHIVinfectionforuninfectedindi- arewellsuitedforuseincombinationwithbiomedicalprevention
vidualswasfocusedonlyonbehavioralinterventions.Althoughthese technologies.Forrecommendationsregardingriskreductioncoun-
continuetobeimportant,effectivebiomedicalapproachesarenow selingforHIV-uninfectedpersons,seeBox1.
available(seeTable4andTable5).Importantly,allbiomedicalpre-
ventiontrialshavealsoincludedstate-of-the-artbehavioralcoun- PreexposureProphylaxis
selingaspartoftheapproach.Thus,HIVpreventionshouldnotbe Preexposureprophylaxis(PrEP)withdailyoralemtricitabine/
consideredaseitherbehavioralorbiomedicalbutratherasacom- tenofovirdisoproxilfumarate(FTC/TDF)asafixed-dosecombina-
binationintervention. tiondecreasesHIV-1acquisitionamongMSM,181serodiscordanthet-
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erosexualcouples,178andheterosexualadults179(Table5).Dailyoral peripheralbloodmononuclearcellscommensuratewithdailyuse
TDFalonewaseffectiveforpreexposureprophylaxisinhetero- wasassociatedwithanestimated99%reductioninHIVrisk(95%
sexualcouples178andpeoplewhoinjectdrugs.180TheUSFoodand CI,96%to>99%).198Incontrast,noefficacywasdiscernedin2trials
DrugAdministrationapproveddailyoralFTC/TDFforHIVpreven- inwhichTDFwasgenerallydetectedinlessthan30%offemale
tionin2013,andtheCDChasissuedguidanceforitsuse.197 participants.182,183
Thekeydeterminantofpreexposureprophylaxisefficacyis Clinicaltrialfindingshighlightimportantconsiderationsforpre-
medicationadherence.DetectionofTDFinplasmahasbeenasso- exposureprophylaxisimplementation,includingthedevelopment
ciatedwithreductioninHIVacquisitionbyapproximately90% ofdrugresistanceamongparticipantsexperiencingacuteretrovi-
amongMSMandheterosexualadults.178,179,181DetectionofTDFin ralinfectionatenrollment,underscoringtheneedtoruleoutacute
Table5.CompletedClinicalTrialsofPreexposureProphylaxisWithAntiretroviralDrugs
Prexposure
Prophylaxis
Relative Detectionin
Reductionin BloodSamples
HIVIncidencein From HIVProtection
Intention-to- Nonserocon- EstimateasRelatedto
Study(Location) Population Design TreatAnalysis verters Adherence Safety
PartnersPrEP 4747Heterosexual 1:1:1 TDF:67%(95% 81% 86%(TDF),90%(FTC Nosignificantdifferencesinthe
Study178(Kenya, menandwomenwith Randomizationto CI,44%to81%) /TDF)Inparticipants frequencyofdeath,serious
Uganda) knownHIV-infected dailyoralTDF,FTC FTC/TDF:75% withdetectable adverseevents,orserum
partners, /TDF,orplacebo (95%CI,55%to tenofovirlevels creatinineorphosphoruslevel
serodiscordant 87%) abnormalitiesbetweenstudy
couples groups
Increasedcreatininelevelsand
decreasedphosphoruslevelsin
lessthan1%ofallpatients
TDF2Study179 1219Heterosexual 1:1Randomization FTC/TDF:63% 79% 78%Excluding FTC/TDFgrouphadhigherrates
(Botswana) menandwomen todailyoralFTC (95%CI,22%to follow-upperiods thantheplacebogroupofnausea
/TDForplacebo 83%) whenparticipantshad (18.5%vs7.1%;P<.001),
noPrEPrefillsfor30d vomiting(11.3%vs7.1%;P=
.08),anddizziness(15.1%vs
11.0%;P=.03);alleventswere
grade1andlessenedafterthe
firstmo
Seriousadverseeventand
laboratoryadverseeventrates
weresimilarbetweenthestudy
groups
Significantdeclineinbone
mineraldensityintheFTC/TDF
groupvstheplacebogroup
Bangkok 2413Injectiondrug 1:1Randomization TDF:48.9% NA NA Nauseamorecommoninthe
Tenofovir users toTDForplacebo (95%CI,9.6% tenofovirgroupvstheplacebo
Study180 to72.2%) group(8%vs5%;P=.02)
(Thailand) Similarfrequencyofdeath,
seriousadverseevents,andgrade
3or4laboratoryresultsbetween
thestudygroups
iPrEx181(Brazil, 2499MSMand 1:1Randomization FTC/TDF:44% 51% 92%Inparticipants Similarratesofseriousadverse
Ecuador,Peru, transgenderwomen todailyoralFTC (95%CI,15%to withdetectable eventsbetweenthestudygroups
SouthAfrica, /TDForplacebo 63%) tenofoviror Nauseamorefrequentduringthe
Thailand,United emtricitabinelevels; first4wkintheFTC/TDFgroup
States) 99%iftenofovir vstheplacebogroup(2%vs<1%;
concentrationswere P<.004)
commensuratewith Creatinineelevations(anygrade)
dailydosing 2%intheFTC/TDFgroupvs1%in
theplacebogroup(P=.08);
majorityoftheeventsgrade1
FEM-PrEP182 2120Women 1:1Randomization FTC/TDF:6% 35%-38%ata UseofPrEPtoolowto TDF/FTCgrouphadsignificantly
(Kenya,South todailyoralFTC (95%CI,−52% singlevisit, evaluateefficacy higherratesthantheplacebo
Africa,Tanzania) /TDForplacebo to41%);no 26%at2 groupofnausea(4.9%vs3.1%;
statistically consecutive P=.04),vomiting(3.6%vs
significant visits 1.2%;P<.01),orelevated
reductionin surroundingthe alanineaminotransferaselevels
HIVincidence infectionperiod (11.4%vs8.6%;P=.03)
VOICE183(South 3019Women(plus 1:1:1 TDF:HR,1.49 ≤30%of UseofPrEPtoolowto Similarfrequenciesofseriousand
Africa,Uganda, 2010women Randomizationto (95%CI,−129% samples;≥50% evaluateefficacy laboratoryadverseevents
Zimbabwe) receivingtenofoviror dailyoralFTC/TDF, to3%;P=.07) ofwomennever comparedwithplacebo
placebogel) oralTDF,or FTC/TDF:HR, haddetectable Nodifferencesinconfirmed
placebo 1.04(95%CI, tenofovirinany phosphorus,transaminase,or
−49.16%to sample urineprotein/glucoselevel
26.98%;NS) abnormalities
Abbreviations:FEM-PrEP,PreexposureProphylaxisTrialforHIVPrevention sexwithmen;NA,notavailable;NS,notstatisticallysignificant;TDF,tenofovir
AmongAfricanWomen;FTC,emtricitabine;HR,hazardratio;iPrEx, disoproxilfumarate;VOICE,VaginalandOralInterventionstoControlthe
ChemoprophylaxisforHIVPreventioninMen;MSM,menwhohave Epidemic.
jama.com JAMA July23/30,2014 Volume312,Number4 399
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