INTEREST11InternationalWorkshoponHIVTreatment,Pathogenesis,and

PreventionResearchinResource-LimitedSettings

Lilongwe,Malawi16-19May2017

TableofContentsIntroduction.............................................................................................................................1HIVinMalawi...........................................................................................................................1EpidemiologyandmanagementofHIVinMalawi...............................................................1HIVtesting............................................................................................................................2EffectsofOptionB+andTestandTreatinMalawi..............................................................2

Progresstowardsthe90-90-90goals.......................................................................................3Introduction.........................................................................................................................3Testing..................................................................................................................................3Treatment............................................................................................................................4ViralSuppression..................................................................................................................4Populationhealthassessmentsandcountryresponses......................................................5

Meetingtheneedsofkeypopulations.....................................................................................7KeypopulationsareatparticularriskofHIVinfection.........................................................7HowcankeypopulationsbeprotectedfromHIVinfection?...............................................8AccesstoHIVcareforkeypopulations................................................................................9

Testingandtreatmentofmen...............................................................................................10Introduction.......................................................................................................................10Innovativetestingoptionsareneededformen–potentialofself-testing.......................10TreatmentofmenlivingwithHIV......................................................................................10

HIV-relatedissuesaffectingadolescentsandyoungadults...................................................11Overview............................................................................................................................11HIVprevention...................................................................................................................11Second-andthird-lineoptionsforchildrenandadolescents............................................12Supportingadherencetotreatmentregimens..................................................................13Useofdigitaltechnologiestoreachadolescents...............................................................13TransitionofadolescentslivingwithHIVtoadultcare–differentiatedcare....................14

Co-morbiditiesupdate...........................................................................................................15TB–improvementsindiagnostics.....................................................................................15HepatitisB..........................................................................................................................17End-of-lifeandpalliativecare............................................................................................18

Conclusion..............................................................................................................................18References..........................................................................................................................19

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IntroductionLilongwe,Malawiwasthehostcityforthe11thInternationalWorkshoponHIVTreatment,Pathogenesis,andPreventionResearchinResource-LimitedSettings(INTEREST),held16-19May2017.MalawiisacentreofexcellenceinHIVresearchanddatawerepresentedfromseveralexcitingprojectsthataretakingplaceintheHeartofAfrica,asMalawiisoftencalled.Asinthepreviousthreeyears,theWorkshopwasdedicatedtothememoryofProfessorJoepLangeandJacquelinevanTongeren,whowerepivotalinestablishingtheINTERESTmeetings,andwhotragicallydiedwhentheirplane(flightMH17)wasshotdownovertheUkraineon17July2014.A total of 506delegates attended theWorkshop:264Malawianhealthcareprofessionals,researchers,students,andcommunitymemberstooktheopportunitytoparticipateactivelyindiscussions,presenttheirownresearch,andinteractwithHIVinvestigatorsfromseveralotherAfricancountries(n=178),Europe(n=48),India(n=3),SouthAmerica(n=2),andNorthAmerica(n=11)1.Livelyconversationstookplaceduringtheformalsessionsandtheculturalandsocialevents.ManydelegatesattendedearlymorningeventsthatwerecomprisedoftheJoep Lange career guidance sessions, poster discussions, and grantspersonship advicesessionsledbyEDCTP,NIH-Fogarty,andANRS2.JacquelinevanTongeren’sinterestsintheartswasreflectedintheartinstallationbyalocalartist, Elson Kambalu, which was displayed during the Workshop, and in severaldemonstrationsofMalawiandancing.Theartinstallation,entitled‘Betweenhumansandagoalpost’,calledonallparticipantsto‘playtheball’andtoreflectonasinglemessageaboutHIVthattheycouldpassontotheircommunities.Duringanoutreachevent,theinstallationwasdisplayedinacommunityinLilongwe,whereitgeneratedmuchenthusiasm.TheMinisterofHealthforMalawi,theHonourableDrPeterKumpalume,openedINTEREST11,welcomingallofthedelegatesandcallingforeveryoneworkingintheHIVfieldtofocusonthemostefficientuseofhumanandfinancialresourcesinordertoendtheHIVepidemic.HesaidthathisambitionwasthatpeoplelivingwithHIV(PLHIV)shoulddiewithHIVandnotfromHIV.HIVinMalawiEpidemiologyandmanagementofHIVinMalawiThepopulationofMalawigrewfrom12.4millionin2004to17millionin2017(1).Analysisofthe population demonstrates that the majority of Malawians are young (<34 years) andsexuallyactive.TheoverallHIVprevalencein2015-2016was10.6%,butthisconcealsbothgenderandgeographicaldifferences3.HIVprevalenceinwomenwas12.8%comparedto8.2%1Presentationsareavailablehttp://www.infectiousdiseasesonline.com/11-interest/2EDCTP(EuropeanandDevelopingCountriesClinicalTrialsPartnership),NIH-Fogarty(USNationalInstitutesofHealth–FogartyInternationalCenter),ANRS(FranceRechercheNord&sud,sida-HIV,Héptatites)3PleasenotethatthefiguresforHIVprevalenceratesinvariouspopulationsinMalawipublishedbytheMinistryofHealth,Malawi,andUNAIDSdifferfromthosepublishedintheMalawipopulation-basedHIVimpactassessment(PHIA).ThisisbecausethePHIAsurveycoveredadifferentperiodfromthegovernmentsurveyandthePHIAdatawerepreliminaryatthetimeoftheINTERESTworkshop.

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inmen.Infectionrateswerefarhigherinthesouthofthecountrycomparedtothenorth:~16%vs.7%.HIVprevalencewas18%inBlantyreCityand12%inLilongwe.Malawihasset itself thegoalofmeeting,by2020, the90-90-90targetsandreducing theincidenceofHIVinfectionto0.2(1,2).ItaimstoendtheHIVepidemicinthecountryby2030.Bytheendof2016,82%ofPLHIVknewtheirHIVstatus;85%ofHIV-positivePLHIVwereonantiretroviraltherapy(ART);and88%ofPLHIVontreatmenthadachievedviralsuppression(1).HIVtestingAsHIVincidencefalls,moretargetedandincreasedeffortsarerequiredtofindnewcasesofHIV inMalawi (1).The introductionofHIVDiagnosticAssistants inmid-2015 resulted inagreaternumberofHIVtestsbeingconducted,butthisdidnottranslateintoagreaternumberofHIVdiagnoses.HIVself-testinghasbeenintroducedinMalawibecauseitisunlikelythatthe90%diagnosisgoalwillbemetbyconventionaltestingmethods(3,4).Self-testingavoidsthepotentialforstigmatisingencounterswithhealthcareprofessionalsandcanbecarriedoutatatimeandplaceoftheperson’schoosing.InMalawi,testingrateshaveincreasedinallagegroupsinmenandwomensinceself-testingwasmadeavailablebutthehighestrateofuptakehasbeenamong adolescents (3). Nearly one half of people (44%) were first-time testers. Qualityassurancecarriedouton1,649testsdemonstratedatestsensitivityof93.6%andspecificityof99.9%.Noadverseeffectsofself-testinghavebeenreported.Approximatelyhalfofself-testerswhotestedHIV-positivehavelinkedtocareandathree-foldincreaseinlinkagehasbeendocumentedifthepersonisassessedandARTisinitiatedathome.EffectsofOptionB+andTestandTreatinMalawiOption B+ for prevention of mother to child transmission (PMTCT) was implemented inMalawi inmid-2011 (5). It resulted inanapproximate two-fold increase in thenumberofwomenutilisingPMTCTinterventionsbetween2010and2012.Numberscontinuedtoriseoverthesubsequentfiveyears.Test and treat was introduced in Malawi in 2016 (1, 5). There was an immediate andimpressiveincreaseinthenumberofmenandnon-pregnantwomeninitiatingARTbutnochangeamongpregnantwomen(Figure1)(1,5).Themajorityoftheestimated690,000PLHIVinMalawi are on ART (69%)(6). The proportion ofMalawianswith viral suppression rosesubstantiallyin2016,butthereisstillroomforimprovementinmenagedover30yearsandwomenaged20-34years(1,5).MostHIV-relatedmortalitynowoccursinPLHIVwhoarenotonART.

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Figure1:ARTinitiationsinMalawisince2010

OvercrowdingatHIVclinicshasstimulatedtheintroductionofdifferentiatedcaremodelsinMalawi (6). The goals of this initiative are to: increase access to HIV care, especially byadolescent girls and boys, youngwomen, andmen of all ages; retain PLHIV in care; andimprovethequalityofHIVservicesinamorecost-effectiveway(1,6).Servicesareadjustedtomeet theneedsofpatientsandproviders, e.g. rapidART initiation, less frequent clinicvisits, more accessible services, task shifting of prescription refill services to healthsurveillance assistants, etc. Holding drop-in clinics at convenient locations and times isfacilitatingaccessforkeypopulationsandworkingpeople.TeenClubsprovidesupportandeducation, as well as health services, for adolescents. Monitoring and evaluation ofdifferentiated care model services is ongoing to ensure that the goals are met withoutsacrificingpatientcare.Progresstowardsthe90-90-90goalsIntroductionImpressive progress is being made towards the 90-90-90 goals in sub-Saharan Africa,especiallythesecond904,thetreatmentgoal(2,7).Preventioneffortshavebeenscaledupanda60%reductioninnewHIVinfectionsinchildrenwasobservedbetween2009and2015(7).However,thenumberofnewadultHIVinfectionshasnotfallenatthesamerate.TestingIn2015,62%ofPLHIVinsouthernandeasternAfricaknewtheirHIVstatus,comparedto36%inWesternandCentralAfrica (7). Innovativeandnon-stigmatisingmethodsof testingarethereforeneededtoreachthe90%‘knowstatus’testingtarget(3,4).Decentralised,home-basedtestingbylaycounsellorshasresultedinarapidscale-upoftestingservicesinsouthernandeasternAfrica.However,confidentialityconcernshaverestrictedfurtherexpansionofthisservice:peoplewantprivacywhenlearningtheirstatusandthisisimpossibleifthelaycounsellorisamemberoftheirowncommunity(3,4).HIVself-testingofferstheopportunity

4By2020,90%ofallpeoplelivingwithHIVwillknowtheirHIVstatus.By2020,90%ofallpeoplewithdiagnosedHIVinfectionwillreceivesustainedantiretroviraltherapy.By2020,90%ofallpeoplereceivingantiretroviraltherapywillhaveachievedviralsuppression.http://www.unaids.org/en/resources/documents/2017/90-90-90

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1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 42010 2011 2012 2013 2014 2015 2016

ART Initiations

Females non-pregnantMalesFemales pregnant

Option B+ Test + Treat

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forpeoplewhoarenotreachedbyothermethodstoascertaintheirstatus.Ithasbeenwellacceptedbyfirst-timetesters,especiallyyoungpeopleandmen;women;repeattesters;keypopulations;andcouples(3,4).Additionalinterventionsareneededafterself-testingtolinkPLHIV to HIV care, HIV prevention (including voluntary medical male circumcision), andtuberculosis(TB)screening.Minimisingthecostofthetestsandimprovingdistributionroutesand linkage to care andprevention areneeded to enhance the cost-effectivenessof self-testing(4).TreatmentIn sub-Saharan Africa, 47% of PLHIV were on ART in 2015, but this figure concealsconsiderabledifferencesinARTcoveragebetweenregions(7).InsouthernandeasternAfrica,54%ofeligiblepatientswereonART,whileonly28%ofPLHIVinwesternandcentralAfricawerebeingtreated(7).TestandTreat,whereARTisofferedassoonasHIVhasbeendiagnosedregardlessofCD4count, isnowbeing implemented inmanysub-SaharanAfricancountries.Simplificationofpre-ARTcare, treatment initiation,andcounsellinghas facilitatedscale-upofARTwithoutimposingfurtherburdensonover-stretchedhealthcareprofessionals(8).RapidinitiationiscriticalforthesignificantproportionofadultsandchildrenwithadvancedHIVdiseasewhoneedtostartARTurgently.Newtreatmentstrategies,includingnoveldrugsand/orformulations,arebeingevaluated(8).Effective,simple,oncedaily,andwell-toleratedregimensthataretakenasonetabletperdayhavefacilitatedtheglobalrolloutofART.However,concernsarestartingtoemergeaboutthe adverse effects of some widely used ARVs, such as tenofovir and efavirenz. Bettertoleratedfirst-lineoptionsthatincludedolutegravir,forexample,arebeingconsidered.Newstrategies, such as long-acting formulations of antiretrovirals (ARVs), are also needed forsomepatients,e.g.toimproveadherence.Itisanticipatedthattheneedforsecond-lineARTwilldiminishasintegraseinhibitorsaremorewidelyusedinfirst-lineregimensbecauseitisbelievedthatvirological failurewillbe lesscommonwiththeseARVs(9).Combinationsofprotease inhibitors and integrase inhibitorsmay provide nucleoside reverse transcriptaseinhibitor(NRTI)-sparingoptionsandbeeffectiveinthepresenceofresistancetoNRTIs.Thepotentialofmobilehealth(mHealth)isbeingharnessedtoenhancetreatmentsuccessbyprovidingHIVeducationandrealtimemonitoring,supportingadherence,andreducingtheneedforclinicvisits(10).ViralSuppressionIn2015,45%ofPLHIVinsub-SaharanAfricaonARThadachievedviralsuppression,butthisfigure was only 12% in western and central Africa. Progress towards the goal of 90% ofpatientsonARTachievingviralsuppressioniscriticallydependentonuniversalaccesstoviralload(VL)testingsothatpatientscanbetestedonaregularbasis(11).TwopresentationsdescribedVLtestingscale-upinKenyaandLesotho,respectively(12,13).ViralloadtestingstartedinKenyain2008:onelaboratoryservedfoursitesand102testswereperformedthatyear(12).In2016,therewere1.5millionKenyanslivingwithHIV,ofwhomapproximatelyamillionwereonART.Sevenlaboratoriescarriedout442,227VLtestsinthecountryin2016.Itwasreportedthat1.479milliontestscouldbeundertakeneachyearwiththe2016capacity.Despitetherapidexpansionoftestingfacilities,itispredictedthatmoreVLcapacitywillberequiredby2019when1.9milliontestsperyearwillbeneeded.Driedblood spot (DBS) samples have been evaluated for VL testing in Kenya: the results were

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acceptable in terms of stability and accuracy. Adopting this optionwill enable peripheralfacilitiestosendsamplestocentrallaboratoriesandincreaseaccesstoVLtesting.LesothoadoptedTestandTreatin2016andintendstoachievethe90-90-90targetsinfivedistrictsbytheendof2017(13).TargetedVLmonitoringwasintroducedin2014forpatientswhowere failing ART; on second- or third-line ART; children <5 years; and pregnant andbreastfeedingwomen. Since June2016, all patientsonART in Lesothohavebeenable toaccessVLtesting.Bytheendof2017,thescale-upoflaboratoryfacilitiesshouldenable>90%ofpatientsonARTtoaccessVLtesting.Thereferralnetworkhasbeenstrengthenedandthefrequencyofsamplecollectionfromhealthcentresincreased.TheVLRocheplatformsattheNationalReferenceLaboratoryareusednowfor16hoursperday.DecentralisedVLtestingisbeingimplementedatdistrictlaboratories.DBSbasedVLtestingisbeingintroducedinhardto reach areas of Lesotho and steps are being taken to ensure uninterrupted VL testingservices.OneofthekeyissuesistoensurethatVLresultsaresenttotheclinicsinatimelymannersothatpatientscanbemanagedappropriately.

PopulationhealthassessmentsandcountryresponsesPopulation-based HIV impact assessments (PHIA) have been carried out in Malawi,Zimbabwe,andZambiausingcommonmethodologiessothattheresultscanbecomparedand combined to increase the power of the analyses (14). The three countries aregeographically contiguous, have similar population size, and are experiencing generalizedcladeCHIVepidemics. Theprimaryobjectivesof thePHIAwere toestimatenationalHIVincidenceratesandsub-nationalprevalenceofVLsuppressioninadults.Inallcountries,thesurveyresponseratewasloweramongmenthanwomen,butmenwhohad agreed tobe interviewedwere just aswilling to undergoHIV testing aswomen.HIVprevalence in women was higher than in men in the three countries (Figure 2)5. HIVprevalenceinchildrenofbothgenderswassimilar inMalawi,butslightlyhigherformalesthanforfemalesinZambiaandZimbabwe.

5PleasenotethatthePHIAfiguresforHIVprevalenceinvariouspopulationsinMalawidifferfromthosepublishedbytheMinistryofHealth,Malawi,andUNAIDS.ThisisbecausethePHIAsurveycoveredadifferentperiodfromthegovernmentsurveyandthedatawerepreliminaryatthetimeoftheINTERESTworkshop.

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Figure 2: Adult HIV Prevalence in Malawi (MPHIA), Zambia (ZAMPHIA) and Zimbabwe(ZIMPHIA)

ViralsuppressionwasdetectedinthemajorityofPLHIVinallthreecountries(59-67.7%),withwomen achieving slightly higher levels of viral suppression than men. Progress towardsreachingthe90-90-90goalsby2030isveryencouraging(Figure3).Figure 3: Progress towards 90-90-90 goals inMalawi (MPHIA), Zambia (ZAMPHIA) andZimbabwe(ZIMPHIA)

ThePHIAdatahavebeenutilisedinNationalAIDSStrategiesandtodevelopHIVpoliciesandprogrammes(15).Continuedinvestmentinhealthsystemsisnecessarytoconsolidateandmaintain thehealth gains alreadyachieved.Given the stabilizationandeven reductionofdonor funding for HIV in recent years, it is essential that domestic funding for HIVprogrammesinsub-SaharanAfricaincreases(16). Innovativemethodsofraisingfundsandring fencing tax receipts for HIV, including AIDS Trust Funds and levies on infrastructure

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spending,areunderconsiderationorbeingestablished.Giventhelimitedsizeoftheformaleconomyinmanysub-Saharancountries, leviesthatraisemoneyfromtheinformalsectorarealsoneeded.DuringtheINTERESTmeeting,severalspeakerswarnedthatthecurrentgainsinHIVcontrolmustbeprotectedandsustainableinterventionsmustbeimplementedtoensurethatthe90-90-90 goals aremet and the AIDS epidemic is ended. There is a window of opportunitybetween 2017 and 2020 to dramatically reduce newHIV infections, but thiswill only beachievedifFast-Tracktactics,asrecommendedbyUNAIDS,areadopted(17).Meetingtheneedsofkeypopulations6KeypopulationsareatparticularriskofHIVinfectionIn2015,keypopulationsinsub-SaharanAfricaaccountedfor20%ofnewadultHIVinfections,demonstratingthatthereareconcentratedkeypopulationepidemicswithinthecontextofgeneralised epidemics driven by heterosexual transmission (18). Key populations are at amuchgreater(10-49times)riskofbecominginfectedwithHIVthanthegeneralpopulation(19).KeypopulationsathighestriskofHIVexposureinclude:menwhohavesexwithmen(MSM),peoplewho injectdrugs (PWID), sexworkers (SW), transgenderpeople,migrants,prisoners, and their sexual partners. Young women in southern Africa, who are also atextremelyhighriskofHIVexposure,areaddressedlaterinthisreport.HIVprevalenceamongMSM is rising, both globally and in sub-SaharanAfrica.HIVprevalence in SW in southernAfricais10-20timeshigherthaninthegeneralpopulation(18).InMalawi,HIVprevalenceratesinfemaleSWsandMSMwere69%and18.2%,respectively,comparedto9.1%inthegeneraladultpopulation(2016data).LevelsofknowledgeofHIVstatusandlinkagetocareareverylowinMSM.HIV-relateddeathshavetripledsince2000inadolescents,withAIDSnowthesecondcauseofdeath inthisagegroupglobally(18).HIVprevalence in prisoners in sub-Saharan Africa ranges from 2.3% to 34.9%, levels that arealmostalwayshigherthaninthegeneralpopulation.Data on HIV prevalence in transgender populations in Africa are limited, but high HIVprevalence has been reported inAsia, e.g.19.3% in Kuala Lumpur,Malaysia and 30.8% inJakarta,Indonesia(19).TransgenderwomenareatparticularriskofHIVinfectioniftheyhavemultiple sexual partners, unprotected anal intercourse, experience depression, undergounsafe hormone and silicone injections, sell sex, or take drugs before sex (20). Stigma,discrimination, and lack of legal recognition of transgender people aremajor barriers toaccessing healthcare and prevention services. This marginalisation also increases thelikelihoodofriskybehaviour.

6Keypopulationsarethosethatarekeytotheepidemic’sdynamicsandkeytotheresponse.UNAIDSconsidersgaymenandothermenwhohavesexwithmen,sexworkersandtheirclients,transgenderpeople,peoplewhoinjectdrugs,andprisonersandotherincarceratedpeopleasthemainkeypopulationgroups.TheirengagementiscriticaltoasuccessfulHIVresponseeverywhere.Thetermkeypopulationsathigherriskalsomaybeusedmorebroadly,referringtoadditionalpopulationsathigherriskofacquiringortransmittingHIVbasedontheepidemiologicalandsocialcontext.http://www.unaids.org/sites/default/files/media_asset/2015_terminology_guidelines_en.pdf

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Despitetheconsiderableneedsofkeypopulations,theiraccesstoHIVservicestendstobeinadequate or non-existent,which itmakes it very challenging to halt epidemics in thesepopulations(18).Criminalisation,stigmatisation,discrimination,andthelackofappropriateservicesarealldriversofHIVtransmissioninkeypopulations.HowcankeypopulationsbeprotectedfromHIVinfection?ImprovingHIVliteracyinallkeypopulationsisanimportantfactorinprotectingthemfromHIVinfection(18).Youngmembersofkeypopulationsareatparticularlyhighriskofinfectionandneedtailoredinformationthataddressestheirquestions.Many barriers toHIV prevention services exist. In prisons, for example, there is a lack ofcontinuity of care between different prisons and between prisons and the community.Overcrowding inAfricanprisons, highHIVprevalence, and criminalisationof sexbetweenmenpreventingcondomprovisiontoprisoners,allfacilitateHIVtransmissioninthissetting.HarmreductionprogrammesforPWIDsarenon-existent,orverylimited,inmostsub-Saharancountries.Provisionofopioidsubstitutiontherapy(OST)andneedle-syringeprogrammesisminimalinthisregionandthisincreasestheriskofHIVtransmissionbetweenPWIDsandtheirsexualpartners.InCanada,whereharmreductionandtreatment-as-preventionprogrammeshave been implemented for PWID living with HIV, PWIDs have experienced substantialdeclines inHIV incidence.Politicalwillandaccesstoresourcesareessential to implementthese prevention initiatives. Criminalisation and stigmatisation of both sex work and sexbetweenmenarecommoninsub-SaharanAfrica,whichseverelyrestrictsaccesstosexuallytransmittedinfection(STI)treatment,condoms,andmedicalcare.Innovative treatment and prevention programmes, as well as outreach testing, are allessential toreachkeypopulationsandtopreventtheepidemicbeingdrivenunderground(18).Overcomingmultipletypesofstigma(external,internalised,andanticipatedstigma)ischallenging, but it is essential if key populations are to access HIV services. In general,attitudestowardsPLHIVandMSMappeartobechanginginmanysocieties,butprogressisslowinsomecommunities.TheuseofinformationtechnologyandsmartphonestoreachkeypopulationsandprovidemHealthisinitsinfancy,butcanprovideconfidential,interactive,andtailoredinformationthatmayhelpindividualsatrisktoaccessservicesand/orberetainedincarewithalowriskofstigma(10).HIVself-testingcanbeusedtoindividualsathighriskofHIVexposurewhoarereluctant to attend clinics due to concerns about confidentiality (3). In South, the IyezaExpressbicycledeliveryservicethatdeliverschronicmedicationtopatientswhoareunableorunwillingtogotohealthfacilitiesisexpandingitsservicestodeliverHIVself-tests.(18).Encouragingdatahaveemergedfromkeypopulationinitiatives.Widespreadprovisionofpre-exposureprophylaxis(PrEP)inSanFranciscohasresultedin10-15%ofpeopleathighriskofHIVexposure,particularlyMSM,usingthisprotectivemeasure. In India,83%ofSWshaveaccessedHIV prevention programmes despite sexwork being illegal and the existence ofwidespreadstigmaanddiscriminationagainstsexwork(18).Asaresult,HIVprevalenceinIndianSWshasfallen.

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AccesstoHIVcareforkeypopulationsBestpracticesinHIVcareforkeypopulationshavethefollowingcharacteristicsincommon(18):

Ø Adoptionofapublichealthapproach.Ø Population-specificservicesandharmreductionstrategies.Ø PrEPforkeypopulationstoprotectindividualsandtheirsexualpartners.Ø Innovativeapproachessuchasself-testingandmHealth.Ø PersonalcontactbetweenhealthcareprofessionalsandPLHIVasthisreducesstigma

anddiscrimination.Ø Tailored,client-centredservices.Ø Protectionofhumanrights.Ø Provisionofsocialjusticeandanappropriatelegalframework.

ComprehensivepackagesofHIVservicesthatareappropriatefortransgenderpeoplecanbedevelopedandhavebeenshowntobeeffective(20).Addressingstigmaandensuringthatsupportive legislation, policies, and financial arrangements are in place are essential forsuccessful service delivery. Community empowerment and addressing violence againstpeoplefromkeypopulationsarealsokeyfactors.Manytransgenderpeopleprioritiseuseofhormone therapy over HIV treatment. It is therefore considered essential for healthcareprofessionals to be aware of potential drug-drug interactions and manage patientsappropriately.Harm reduction programmes are starting in some sub-Saharan African countries, such asSouthAfricaandKenya.However, there is limitedpoliticaland financial support for theseprogrammes,despiteevidenceoftheireffectivenessinreducingtheriskofHIVinfectioninPWID(18).OSTandneedle-syringeprogrammeswereintroducedinMauritiusin2006,whenPWIDaccountedfor92%ofnewHIVinfections.In2011,OSTwasextendedtoprisons.Whenanewgovernmentwaselectedin2014,theharmreductionprogrammeswerediscontinuedand,forthefirsttimeinadecade,HIVincidenceincreasedinPWIDfrom31%in2014to35%in 2015. This demonstrates that HIV epidemics can only be controlled by ongoing andsustainedHIVprogrammesforkeypopulations.Decriminalisingsexwork,eliminatingsexualviolence,and increasingARTcoverageamongSWsinKenyawouldsubstantiallyreduceHIV incidenceamongbothfemaleSWsandtheirclients(18).SouthAfricahaspromisedtosupplyPrEPfor3,000SWs,usingmobileunitstosupplyitandotherHIV,TB,andSTIservicesincommunities,inanattempttoprotectthemandtheirclients.HealthcareprofessionalsarebeingtrainedtonotdiscriminateagainstSWsandtobesensitivetotheirneeds.Linkagetocarereached57%in2015.HIVservices(diagnosis,treatment,andmonitoring)forpeopleatriskofimprisonmentandthosealreadyinprisonsarestartingtodevelopinanumberofsub-SaharanAfricancountries(18). The aim is to provide care both inside andoutside of the prison environment. Peereducation and provision of condoms have been introduced in some prisons. Despite thepotentialofPrEPandpostexposureprophylaxis (PEP) toprotectprisoners from infection,accesstotheseinterventionsisalmostnon-existent.

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There is a high level of interest in PrEP amongMSM in South Africa and demonstrationprojectshaveyieldedencouragingdataaboutacceptabilityandadherence(18).Linkagetocare,however,hasbeenlow,evenincitieswithhighqualityandaccessibleHIVservices.Reaching the ‘last 10%’ will require innovative, creative, and dispersed HIV services thatengagewith keypopulations and gobeyondhealthcare. Serviceshave tobe confidential,appropriate,efficient,relevant,andclientcentred.TestingandtreatmentofmenIntroductionHIVtestingandtreatmentofmenhashistoricallylaggedbehindthatofwomen.NumerousbarriersthatpreventmenfromaccessingHIVserviceshavebeenidentified,withstigmabeingamajorfactor.Thereisaclearneedformen-friendly,easily-accessibleclinicswithflexibleopeningtimessothatmencanaccessthemwithoutlosingpaidworkand/orincurringhightransportationcosts.Innovativetestingoptionsareneededformen–potentialofself-testingSelf-testingisattractivetomenbecauseofitsconfidentialityandflexibility(4).Theyfinditmore acceptable to self-test in the privacy of their own homes than risking stigmatisingencounters at clinics orworkplace testing sites. Self-testing can also be used to promotecouplestesting(3,4).Sofar, thesehasbeennoevidenceofan increasedriskofpotentialadverseeffectsof self-testing, suchas intimatepartner violence,homicide,or suicide (3).Linkage to care, once diagnosed, is 42-56%. A small proportion of respondents (3%,287/10,007)inastudyconductedinMalawireportedthattheyhadbeen‘forcedtotest’bytheirpartner,but94%oftheseindividualsalsosaidthattheywouldrecommendself-testingtotheirfriendsandrelatives.TreatmentofmenlivingwithHIVInvolving men in HIV prevention and treatment programmes is critical to the success ofhaltingHIVtransmission(5,21).FactorsthatincreasethelikelihoodofmenparticipatinginHIVcareincludedecentralizedhealthfacilitiessothatmostpeoplecanwalktothem,routine3-6 month appointments rather than monthly clinic visits, and elimination of diagnostichurdles (CD4 cell count, VL) prior to starting therapy (Test and Treat) (5). Incentives toencouragemen to attend antenatal clinics, e.g. fast track appointments for womenwhoattendwiththeirpartners,havebeenpartiallyeffectivebuthavealsohadunwantedeffects,such as the phenomenon seen inMalawi of ‘husbands for hire’. However, implementingOptionB+ inMalawi, forpreventionofmother-to-childtransmissionandkeepingmothersalive,resultedina25%increaseinthenumberofmenstartingART(5).ImplementingTestandTreatresultedina‘wave’ofmenwhowerealreadyinpre-ARTcareinitiatingART.Itisnotyetclearifthisincreasewillbemaintainedinthelongterm.In2016,~55%ofmeninneedofARTwerebeingtreatedinMalawi.ItisparticularlyimportantthatmenlivingwithHIVaged30-44yearsaresuccessfullytreatedsincetheyaremorelikelythanyoungermentotransmitHIV to young women. Partner testing and counselling leads to better uptake of, andadherenceto,ART.TreatingHIV-positivemenpreventsfather-to-(HIV-negative)-mother-to-childHIVtransmission.ItisanticipatedthatuniversalTestandTreatwillreducetheoverallpopulationVL,whichwillhelpprotecteveryonefrominfection.

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HIV-relatedissuesaffectingadolescentsandyoungadultsOverviewINTEREST11addressedanumberofissuesaffectingadolescentsandyoungadultslivingwithHIV, especially in resource-limited settings. This large and growing population group isheterogeneous,withdiverseneedsandexperiences.Someyoungpeopleareinschool,someareworkingformallyorinformally,andyetothersareunemployed.Someareinstablesexualpartnerships,somehavesequentialrelationships,andsomehavenon-exclusiverelationships,while others are not sexually active. Some are already parents and some are caring forsiblings, while others have no childcare responsibilities (21). This diversity underpins theimportanceofinvolvingyoungpeopleinthedesignofHIVprevention,treatment,andcareand support HIV services that are tailored for their individual needs. It highlights theimportanceofdifferentiatedcareandservicedelivery(www.differentiatedcare.org)ratherthan ‘one size fits all’(22). Addressing the determinants of stigma and discrimination,includinginternalisedstigma,iscriticaltoenhancingthehealthandwell-beingofadolescentsandyoungadultseverywhere,regardlessofHIVstatus.HIVpreventionYoungwomen(15-24years)bearadisproportionateburdenofHIVinfectioninsouthernandeasternAfrica.TheyareuptoeighttimesmorelikelytoacquireHIVthanareyoungmen;almostthree-quarters(74%)ofyoungpeopleinthisagegrouplivingwithHIVinsub-SaharanAfricaaregirlsoryoungwomen(21,23).TheUNPoliticalDeclarationonEndingAIDSsetthegoalofreducingnewinfectionsinadolescentgirlsandyoungwomento≈100,000by2020(21).AmongthemanybarriersstandinginthewayofachievingthisobjectiveissuboptimalcomprehensiveHIVknowledgeandcondomuseamongyoungsub-SaharanAfricanwomen.InruralKwaZulu-Natal,SouthAfrica,morethan30%ofpregnantwomenareunder20yearsofageandoneinfiveofthesewomenalreadyhasHIV(23).Bytheageof23years,half(50%)ofpregnantwomeninthisregionhaveHIV.Ifawoman’spartneris4ormoreyearsolderthansheis,shehasariskofacquiringHIVinfectionthat isfrom4to8timeshigherthanifherpartnerisofasimilarage.HIVinfectionstudiesamonghighschoolstudentsinruralKwaZulu-Nataldemonstratethatgirls,especiallythosewitholdersexualpartners,aremorelikelytobeHIV-positivethanboysoftheirage.Despitereportingalowfrequencyofsexualactivity,girlsandyoungwomenaremorelikelytoengageinunprotectedsexwhentheyaresexuallyactive. The dynamics of HIV transmission in this population have been studied usingphylogeneticanalyses(23).Theyshowthatyoungwomenunderage25yearsareacquiringHIV fromoldermen (25-40years),whothemselvesareoftenalso ina relationshipwithawomanoftheirownage.Youngerwomenmatureintotheoldercohortofwomenaged25-40years,whentheythentransmitHIVtosimilarly-agedmalepartners.AcommunitystudyinanurbanandruralareaoftheEasternCapeinvestigatedsecondaryHIVtransmissionamongSouthAfricanadolescents(24).Datawereobtainedfromalongitudinalpanel study of 1060 HIV-positive and 467 HIV-negative adolescents, as well throughqualitative research conducted with 80 youth. The majority of the participants in thelongitudinal panel lacked basic necessities (68%) and 90% were orphans (44% maternalorphans,30%paternalorphans;16%doubleorphans).Athird(33%)didnotknowtheirHIVstatus. One quarter of the sample reported at least one high-risk sexual practice in thepreviousyear.Non-adherencetoantiretroviraltreatment(ART)wasself-reportedby36%ofthe young people livingwith HIV. Twelve percent of those livingwith HIV reported both

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unprotectedsexandnon-adherencetoART,placingthemathighriskofongoingsecondaryHIVtransmission.The CAPRISA 004 study demonstrated that presence of genital inflammation prior toHIVexposurerenderedwomenmorevulnerabletoHIVacquisition(OddsRatio:3.2,95%CI1.3-7.9) (23). If Prevotella bivia bacteria were present in the vagina, the risk of genitalinflammationwas19timeshigherandtheriskofacquiringHIVwas13timeshigherthaniftheywereabsent.Thecompositionofthevaginalmicrobiomeappearstoaffecttheefficacyofpre-exposureprophylaxis(PrEP)usingtenofovir:ifLactobacilluswasthedominantvaginalmicrobe, tenofovir vaginal gel PrEP was 78% protective compared to 26% when non-Lactobacillus strainsdominated. In vitro experimentshavedemonstrated that tenofovir israpidlydepletedbyGardnerellastrainsbutnotbyLactobacillus(3).Young women need choices to interrupt the cycle of HIV transmission, including PrEP,voluntary medical male circumcision (VMMC), antiretroviral therapy for all PLHIV, andimprovedmethodsofHIVcounsellingandtesting,suchasself-testingwhichiswellacceptedbyadolescentgirls(3,4,21,23).Ifconfirmedinfurtherstudies,vaginalprobioticstoenhanceLactobacillusdominancemayreduceHIVriskandenhancePrEPefficacy.Twotrialsofvaginaldapivirinerings(replacedmonthly)reportedmoderateeffectivenessinolderwomenbutnotinthoseunder25(21,25,26).Thismayhavebeenduetoloweradherenceassociatedwithlow risk perception, differences in vaginal microbiome, or other factors. Multipurposetechnologies,suchascombinationcontraceptiveandHIVpreventiondevices,maybemoreattractivetoyoungwomenandthusimproveadherence(21).Trialsofsuchdevicesareonlyjustbeginninginsmallnumbersofwomen.TheDREAMSprogrammeaimstoreduceHIVincidenceinadolescentgirlsandyoungwomeninprioritisedareasby40%inthreeyears(21).Tailoredprogrammesincludemaleandfemalecondom provision and promotion, HIV testing (including self-testing), post-violence care,contraceptivemethods,socialassetbuilding,PrEP,school-basedHIVandviolencepreventionprogrammes,familystrengtheninginitiatives,andmalesexualpartner-focusedstrategiestoreduceHIVtransmission, includingVMMC.Thebestoutcomesarebeingobservedwhenayoungwomanutilisesatleastsixofthesesupportmechanisms.Second-andthird-lineoptionsforchildrenandadolescentsThe WHO recommendations for second-line ART regimens for children and adolescentsdepend on the initial regimen taken (11). In all second-line regimens, a dual nucleosidereversetranscriptase inhibitor(NRTI)backboneisutilised,withthethirddrugfromaclassdifferent tothat in the first-lineregimen.Comparingresponsestosecond-lineARTcanbechallenging because of variations in the definitions of virological failure and duration offollow-up used in clinical studies (27). AUgandan study of second-line ART (2NRTIs pluslopinavir/ritonavir)in60children<12yearsolddemonstratedvirologicalsuccess(pVL<1000copies/mL)in~80%ofpatientsat24months(28).Nomutationsassociatedwithresistancetoproteaseinhibitorsweredetectedinthesmallnumberofvirologicalfailuresthatoccurred,andallpatientswereabletoregainvirologicalcontrolafteradherencecounselling.Themajorfactorsassociatedwithsecond-linetreatmentfailureinchildrenandadolescentsarepooradherence,presenceofphysicalwastingatthestartofsecond-lineART,havingAIDSprior to first-lineART, baseline CD4 cell count less than 100 cells/mm3, having virologicalfailurepriortoadolescence,initiatingARTasanadolescent,andnon-disclosureofHIVstatus

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(27).Havingagrandparentasacaregiverornothavingacaregiveratallwerealsoassociatedwithvirologicalfailure.Medicationfactorsincludedadverseevents,poorpalatability,initialnon-nucleosidereversetranscriptaseinhibitor(NNRTI)regimen,anddrug-druginteractions.Health system factors associated with second-line failure included stock outs, limited VLmonitoring, long waiting times at clinics, and poor healthcare worker knowledge andattitudes.Socialfactors,suchasstigma,longdistancestoclinics,costoftransporttoclinics,andlackoffood,alsoincreasetheriskofsecond-linefailure.Allofthesefactorsinteract:riskof virological failure increases as the number of adverse factors experienced by a youngpersonlivingwithHIVrises.TheWHOrecommendsdarunavir/rand/orraltegravir(ordolutegravir)with(or, inspecificcases,without)1-2NRTIsasthird-linetherapyforchildrenandadolescents(11).Insettingswhereitispossibletoperformresistancetesting,thepresenceofdrugresistancemutations(DRMs)canbeusedtopredictsusceptibilitytothird-lineARVs(27).InitiativessuchtheNewHorizons programme are increasing access to second- and third-line antiretroviral drugs(ARVs) and provide educational and capacity building support. Of five children who hadbenefitedfromthisprogramme,allhadachievedvirologicalsuppressionontheirthird-lineARTregimen(followup:6-54months)(27).SupportingadherencetotreatmentregimensAdolescent girls in sub-Saharan Africa tend to have low rates of adherence to ART and,consequently, sub-optimal levels of viral suppression (21). Among the adherence supportmeasures for caregivers of children living with HIV and for adolescents themselves aremedication reminders, pill boxes, cell phone messages (appointment and medicationreminders),peersupportgroups,timelydisclosureofHIVstatus,andsocioeconomicsupport(27).RiskfactorsforsecondaryHIVtransmissionfromyoungpeoplearealcoholuse,stigma,foodinsecurity, having been horizontally infected with HIV, and being in a relationship.AdolescentswiththreeormoreoftheseriskfactorswerehighlylikelytotransmitHIV(24).Providingsocialsupport,food,andclosermonitoringreducedtheriskofnon-adherencebyatleast50%.ProgrammesthataddresstheseissuescanhelpimproveadherenceandreducesecondaryHIVtransmission.UseofdigitaltechnologiestoreachadolescentsRuraladolescentsfaceparticularchallengesinaccessinghealthcare:theclinicmaybealongwayfromtheyoungperson’shomeandfindingthemoneyandtimetotraveltherecanbeverydifficult.mHealthservicescanhelpyoungpeopleinsuchsettings:weeklytextmessagemedicationremindersandreal-timemonitoringstrategiescanimproveoutcomes(10).Insub-SaharanAfrica,themajorityofadolescentsownamobilephoneorsmartphone:inonestudy,64%of16-18yearoldsownedaphoneorsmartphone(10).Smartphonesalesareforecasttogrowby40%peryearinthisregion(10).Althoughadolescentsusephonespredominantlyformessaging,music, andgames, theyarealsoaccessing informationabouthealth,HIV, andemploymentusingtheirphones.DevelopmentisunderwayofmoremHealthapplications(apps)thatrespondtoadolescents’needs(bothHIV-relatedandotherissues)andarerelevanttolocalconditionsisunderway(10). Emojis, educational gaming, and avatars make apps more attractive. Involvingadolescentsindesigningandupdatingappsisessential.Chatappscanprovidesupportandinformation in an anonymous setting, which diminishes the risk of potential stigmatising

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encounterswithprofessionalsorlaycounsellors(10,29).Electronicmonitoringofsymptomsreducestheneedforfrequentclinicvisits,which isbeneficial forbothyoungpeople livingwithHIVandhealthcareprofessionals(10).Losstofollow-upcanbereducedthroughongoingregularcommunicationbetweenadolescentsandhealthcareworkers.TheuseofdigitalcashappsforhealthsavingsandhealthcareincountriessuchasKenya,7andelectronicmedicalrecords in places such as Cape Town, South Africa8, are enhancing HIV health care foreveryone,includingadolescentsandyoungpeople.TransitionofadolescentslivingwithHIVtoadultcare–differentiatedcareAs adolescents transition from being dependent children to independent adults, theirhealthcareneedsarechangingfrompaediatrictoadultcareatatimethattheyarealsofacingmanyotherchallenges(Figure4)(30,31).ThisperiodisfraughtwithpotentialdifficultiesforadolescentslivingwithHIV,includingnon-adherence,poorviralsuppression,mentalhealthproblems,stigma,highlosstofollowup,andanenhancedriskofAIDSmortality.ItisalsoatimewhensecondaryHIVtransmissiontosexualpartnersandtooffspringishigh;addressingtheseroutesoftransmissionisessentialtobreakthecycleofHIVinfection(31).InterventionssuchasdelayingchildbearinguntilanadolescentlivingwithHIVisinastablerelationshipandisonsuccessfulARTcandramaticallyreducetheriskofonwardHIVtransmission.Figure4:IssuesfacedbyadolescentslivingwithHIVastheytransitiontoadultcare

TheInternationalAIDSSociety,inassociationwiththeCollaborativeInitiativeforPaediatricHIV Education and Research (CIPHER), has produced a special supplement on adolescenttransition(32).Thedifferentiatedcareandservicedeliverymodelprovidesaframeworktodesignhealthcareandpsychosocialservicesthatmeetadolescents’needsforHIVpreventionandtreatment(22,31).AdolescentretentionincareisimprovedthroughaccessibleweekendclinicsthatprovideARTrefills,healthcare,andpsychosocialsupport(31).TeenClubshave

7OluluM.Lessonsfromimplementation.11thInternationalWorkshoponHIVTreatment,Pathogenesis,andPreventionResearchinResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.8DeVegaI.Importanceofuniqueidentifiersandplatforms.11thInternationalWorkshoponHIVTreatment,Pathogenesis,andPreventionResearchinResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.

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proved very popular and effective in Malawi. Adherence and viral suppression amongadolescents who attend these clubs are equivalent to those seen in adult clinics, withadolescenttherapeuticoutcomessuperiortothoseseeninadolescentswhodonotattendTeenClubs.ThesuccessofTeenClubs isanchored in their responsiveness toadolescents’needs:preparingadolescents for lifewhilebeinga forum formeeting friends.Nowaitingtimesandminimalorzerotransportcostsmakeclubsattractivetoadolescents livingwithHIV.InMalawi,theTransitionTraining(T2)programmeforyoungadults(18-24years)whohavegraduated from secondary schoolhasbeendevelopedby adolescents livingwithHIVandvolunteers(31).ItincludestheT2ToolBox.Thissetoftoolsprovideseducationandsupportforself-healthcare,alongwithlifeskillsforemploymentandeducation.KnowledgeofarangeofHIV, sexualhealth,personal skills, andemployment topics increased substantially afterattending ten sessions of the T2 programme. Adherence and viral suppression wereconsiderablyhigherinprogrammegraduatesthaninadultsattendingthelocalclinic.TheT2programmeencouragedadolescentslivingwithHIVtotransitionfromTeenClubstobecomementorstoyoungeradolescents,whichfacilitatesadolescentHIVprogrammesustainability.InnovativemethodsofHIVprevention,care,andtreatmentservicedeliverytoadolescentsandyoungadultswillhelptopreventHIVinfectionandensureeffectivetreatmentforthoselivingwithHIV.Co-morbiditiesupdateTB–improvementsindiagnosticsThediagnosisoftuberculosis(TB),especiallyinco-infectedHIV/TBindividuals,isanimportantopportunitytoidentifyandtreataconditionthatisassociatedwithahighburdenofmorbidityand mortality (33-35). The GeneXpert assay has been described as the most importantadvanceinthediagnosisofTBinacentury(33).However,itsusehasnotimprovedmorbidityandmortalityoutcomes in intervention trials (36).There is stillanunmetneed for simplediagnostic TB tests that can be used in community settings. The clinical potential of thelipoarabinomannan(LAM)TBdiagnosticassaywasdiscussedduringINTEREST11(33).LAMisalipopolysaccharidemycobacterialcellwallstructuralcomponentthathasimmunogenicandimmunemodulatoryactivity(Figure5)(33).TheAlereDetermine™TBLAMAntigen(TBLAMLFA)LateralFlowTestincubates60µLofurinefor25minutesatroomtemperature.Theteststripisthencomparedwiththereferencescale.Ina2015WorldHealthOrganization(WHO)review,theoverallagreementbetweenTB-ELISAandTBLAMLFAwas507/516(98.3%,95%CI: 96.7-99.2), giving a Kappa value of 0.84 (95% CI 0.72-0.92). Inter- and intra-readervariabilitywasconsideredtobehigh.

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Figure5:LAMstructure

TheLAMLFAhasnumerousadvantages:lowcost($3.50/test),pointofcare(POC)use,easeandsafetyofobtainingaurinespecimencomparedtosputumexpectorationorinduction,availabilityof results in25minutes,simplicityof thereadoutwithnohardwarerequired,rapidityof diagnosis spporting rapid treatmentdecisions, andminimal biosafety concerns(33).However,anumberoffactorsaffectthesensitivityoftheassay:thechoiceofreferencestandard, thecut-off thresholds,observervariability,urineconcentration,variablestorageconditions, urine contamination, and the population being studied. These limitations ledWHOtoadvisein2015thatLAMshouldnotbeusedforTBdiagnosisandscreening,butthatitcouldbeusedtoassist inTBdiagnosis invery immunocompromisedorseriously illHIV-positive patients with signs and symptoms of TB (www.who.int/tb/areas-of-work/laboratory/policy_statement_lam_web.pdf).Since50%ofco-infectedpatientswhodiefromTBhavenotbeendiagnosedwithTBpriortodeath,itiscriticalthatbetterdiagnosticmethodsaredevelopedtoidentifyTBinthispopulation.ACochranereviewoftheaccuracyofLAMLFAforthediagnosisandscreeningofactiveTBdiseaseinHIV-positiveadultshasshownthatthetesthaslowsensitivityfordiagnosisinHIV-positiveadultsorscreening,buthasutilityinseriouslyillpatients(37).ThishasstimulatedresearchintothesourceofLAMantigensinseriouslyill,co-infectedpatients.Itbecameclearthatdyingmycobacteriawerenotthemajorsupplyoftheantigensandtherewasnoevidenceofsignificantproteinleakagethroughtherenalglomerulus.AnanalysisofrenalhistologyinacohortofHIV-positiveadults inUgandademonstratedthatrenalTBwaspresent in8/13LAM+patients,eventhough7/13LAM+patientswerenotonanti-TBtherapyatthetimeofdeath(38).RenalTBaccountedforLAMpositivityinthemajorityofpatients.However,somepatientswithdisseminatedTBbutwithout renal involvementwerealsoLAM+, suggestingthat other mechanisms could be responsible for urinary LAM positivity in a minority ofpatients.A comparison of sputum- and urine-based diagnostic assays for HIV-associated TBdemonstratedthaturineLAMwas100%sensitiveinveryanaemicpatients(haemoglobin<8)butwaslesssensitiveinthosewithhaemoglobin>8(39).RenalTBoccursinverysickHIV/TBco-infectedpatientsandisstronglyassociatedwithaverypoorprognosis.Thereis,therefore,arationaleforroutineurineLAMtestinginsick,hospitalisedHIV-positivepatientstoidentify

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TBco-infectionandfacilitaterapidinitiationofTBtherapy.Thisconceptisbeingevaluatedina three-year study - Screening for Tuberculosis to Reduce AIDS-Related Mortality inHospitalized Patients in Africa (STAMP) that started in 2015. STAMP is a randomizedcontrolled trial to assess the clinical outcomes of standard sputum-based testing withGeneXpert MTB/RIF plus additional urine-based LAM screening compared to standardscreeningalone.Community-basedHIVtestingcampaignsbylayhealthworkershavebeenusedtoidentifypeoplewithsixself-reportedsignsandsymptomsofTBinBotswana(34).Thesigns/symptomsofTB (SSTB)were:coughor fever formorethanatwo-weekduration; lymphadenopathy;haemoptysis;nightsweats;orunexplainedweightloss.EveryonewithSSTBwasreferredtoacommunity clinic, regardless of their HIV status, and linked to care. Compared to PLHIVwithoutSSTB,PLHIVwithSSTBweremorelikelytobenewlydiagnosedwithHIV,notonART,andtohaveafamilymemberwithTB.Thisstudydemonstratedthatcommunity-basedHIVandTBcaseidentificationbylayhealthworkerswasfeasibleandresultedintheidentificationofmanypeoplewithTB,especiallyco-infectedPLHIV,whowerelinkedtocareforbothHIVandTB.GeneXpertisbeingusedinMalawitodiagnoseTBamongPLHIVwithpresumptiveTB.Theresultsofacross-sectionalanalysisofroutinehealthcaredatacollectedbetweenApril2014andJune2016in21TB/HIVintegratedclinicsinMalawiwerepresentedatINTEREST11(35).Overthisperiod,theproportionofHIV-positivepeoplewhowerealsopresumptiveTBcasesincreased. However, coverage of GeneXpert was sub-optimal: <50% of PLHIV. TheinvestigatorsrecommendedthatallPLHIVwhoaresuspectedofbeingco-infectedwithTBshould have access toGeneXpert and start TB treatment immediately if pulmonary TB isdiagnosed.HepatitisBMorethan50%ofliver-relatedmortalityassociatedwithhepatitisB(HBV)orC(HCV)globallyoccursinsub-SaharanAfrica(40).NorthAfrica,particularlyEgypt,hasthehighestprevalenceofchronicHCVinfectionintheworld9.InUganda,where52.3%ofpeoplehavebeenexposedtoHBV,theoverallprevalenceofHBVchronicinfectionis10%.ThesefiguresconcealwidedisparitiesbetweenregionsintermsofHBVprevalence:levelsof23.9%havebeenobservedin the north west compared to 3.8% in the south east. HBV is transmitted primarily byhorizontalroutes(mainlysexualcontact).PeoplewithhighlevelsofHBVDNAaremorelikelytotransmitthanthosewithlowHBVDNAlevels.InareaswhereHBsAg(HBVsurfaceantigen)prevalence is >2%, vertical transmission from mother to baby is common. Occult HBVinfectionhasbeenidentifiedin30%ofpatientsadmittedtotheemergencyroominMulago(94/314samples),suggestingthatHBVcouldbetransmittedviabloodtransfusionsinUganda.Treatment options for HBV mono-infection are limited in sub-Saharan Africa and livertransplantation is not available.HBVhas been shown to inducehepatocellular carcinoma(HCC) inyoungadults:data frompatientsmanagedat14centresacrossAfricahavebeenanalysed.ThemostfrequentagerangeatHBV-relatedHCCdiagnosisinnon-EgyptianAfricancentreswas32.5-37.5years,whichis~20yearsyoungerthaninEgypt.Themediansurvival

9BostanN,MahmoodT.AnoverviewabouthepatitisC:adevastatingvirus.CritRevMicrobiol.2010May;36(2):91-133.

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was2.5monthsinnon-EgyptianAfricancentres,comparedto10.9monthsinEgypt(p<0.01).TheWHOhasdeveloped its firsteverGlobalStrategyonViralHepatitis2016-2021,whichaimstoeliminateviralhepatitisasamajorpublichealththreatby2030.IncreasedaccesstoHBVtesting,vaccination,andtreatment,aswellaseducationofthepublicandhealthcareprofessionals,areessentialtoreachthisgoal.HIV/HBV co-infection is the causeof growinghealth problems in sub-SaharanAfrica (41).Infection with both viruses leads to complex immunological interactions that result inincreasedfibrosisandsub-optimalimmuneresponsestoHBV,whichmeanthatthevirusisnot cleared even with tenofovir treatment. In resource-limited settings, access to HBsAgtesting is limited; as a result,many co-infected patients are not identified. There is littleinformationaboutthenaturalhistoryofco-infectioninthesesettings.InadequateaccesstoHBVvaccination,liverdiseasefibrosisassessmentmethods,andvirologicalmonitoringofHBVDNAcompromisestheabilityofhealthcareprofessionalstopreventandtreatHBVinfectionandpreventdiseaseprogression.AdvocacyeffortsareongoingtoimproveawarenessofHBV;increase government commitment to preventing and treating HBV; extend coverage ofdiagnostics, prevention and treatment options for HBV; and promote the WHO GlobalStrategy(42).End-of-lifeandpalliativecareEnd-of-lifeandpalliativecarehavenottraditionallyreceivedmuchattentioninsub-SaharanAfricahealthcaresystems(43).In2003,theAfricanPalliativeCareAssociation(APCA)wassetuptoaddressthisissue:itsvisionistoachieveaccesstopalliativecareforallinAfrica.APCAsupports programmes in 29 African countries andworks to ensure that palliative care isintegratedintohealthsystemsatalllevels.IncreasingknowledgeandawarenessofpalliativecareamongallstakeholdersandbuildingtheevidencebaseforpalliativecareinAfricaarekeystrategicobjectives.APCAofferstechnicalassistancetoMinistriesofHealthandrelevantstakeholders in relation to policy development; education; essential medicines andtechnologies; implementation of service delivery framework standards; organisationaldevelopment;and research.Nationalpalliative carepolicieshavebeendeveloped in8/54Africancountries,thankstoAPCA’ssupport.Thephilosophyis:‘Inpalliativecare,itisgoodtohope for the best but prepare for the worst’. Comprehensive planning and goodcommunication are the keys to good end-of-life care. In most African countries,comprehensiveformalend-of-lifecarecannotbeprovided,andsoitisnecessarytousefamilyandcommunityresourcesinconjunctionwithprofessionalsupporttoachieveaholisticandoptimalend-of-lifeexperienceforthepatientandfamily.ConclusionDuring the closing session, the winner of the Joep Lange Award was announced. It wasAugustineChokoofMalawiwhohadpresentedverypositiveandinterestingdataonOneyearoutcomesfollowingavailabilityofHIVself-testinginBlantyre,Malawi(3).ThechairsofthemeetingpraisedthespiritandlivelinessoftheWorkshop,aswellasthehigh-qualitydatathathadbeenpresentedbyallofthespeakers.TheythankedtheWorkshopsponsors,thelocalorganisingcommittee,theinternationalandscientificcommittees,andallofthepeoplewhohadmadethemeetingasuccess.The locationof INTEREST12,tobeheld in2018,willbeannouncedshortly.

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References1. KaluaT.HIVinMalawi.11thInternationalWorkshoponHIVTreatment,Pathogenesis,and Prevention Research in Resource-Limited Settings (INTEREST); 16-19 May; Lilongwe,Malawi.2017.2. Joint United Nations Programme on HIV/AIDS (UNAIDS). 90-90-90. An ambitioustreatmenttargettohelpendtheAIDSepidemic.2014.3. Choko A. One year outcomes following availability of HIV self-testing in Blantyre,Malawi. 11th International Workshop on HIV Treatment, Pathogenesis, and PreventionResearchinResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.4. CorbettEL.Progresstowardsthefirst90insub-SaharanAfrica:innovativeapproaches,including self-testing. 11th InternationalWorkshoponHIV Treatment, Pathogenesis, andPreventionResearchinResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.5. JahnA.OptionB+andMalePartnerInvolvement. 11thInternationalWorkshoponHIV Treatment, Pathogenesis, and Prevention Research in Resource-Limited Settings(INTEREST);16-19May;Lilongwe,Malawi.2017.6. Ngoma S. What does differentiated care look like in Malawi? 11th InternationalWorkshoponHIV Treatment, Pathogenesis, andPreventionResearch inResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.7. AkadiriK.ProgressinHIVpreventionandtreatmentscale-upinsub-SaharanAfrica.11thInternationalWorkshoponHIVTreatment,Pathogenesis,andPreventionResearchinResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.8. Conradie F. ART rapid scale up: implications for patient care and retention. 11thInternational Workshop on HIV Treatment, Pathogenesis, and Prevention Research inResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.9. Cesar C. Treatment sequencing: second and third line ART in the era of integraseinhibitors. 11th InternationalWorkshoponHIVTreatment,Pathogenesis, andPreventionResearchinResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.10. Carty C. Reaching Adolescents: Tailoring resonant technologies: mHealth. 11thInternational Workshop on HIV Treatment, Pathogenesis, and Prevention Research inResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.11. World Health Organization. Consolidated guidelines on HIV prevention, diagnosis,treatment and care for key populations. 2016 update 2016 [Available from:http://www.who.int/hiv/pub/guidelines/keypopulations-2016/en/.12. AbuyaD,OnkendiE,BowenN,etal.FieldevaluationofRocheFVEDBSProtocol.11thInternational Workshop on HIV Treatment, Pathogenesis, and Prevention Research inResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.13. PhalatseM. Lesothoviral load scale-upplan. 11th InternationalWorkshoponHIVTreatment,Pathogenesis,andPreventionResearchinResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.14. KaluaT.MeasuringImpact–PHIAFindingsfromMalawi,Zimbabwe,andZambia11thInternational Workshop on HIV Treatment, Pathogenesis, and Prevention Research inResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.15. Cai H. Programmatic Uses and Policy Implications of ZAMPHIA Data. 11thInternational Workshop on HIV Treatment, Pathogenesis, and Prevention Research inResource-LimitedSettings(INTEREST);16-19May;Lilongwe,Malawi.2017.

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