MaKInGIT COUNT BRIEFInGShEET 8 MICROBICIDES thisMaking it Count briefingsheetprovidesanoverviewonthecurrentstatusofresearchtowardsthe developmentofmicrobicidesforsexualhealthpromotersworkingwithgaymen,bisexualmenandothermenthat havesexwithmen(MSM).Microbicidesoffertheprospectofamuch-neededadditional HIVpreventionoption. avaginalmicrobicidecontaininganantiretroviraldrughasalreadybeenshowntoreducewomen’sriskof HIV infectionbutrectalmicrobicidesareatamuchearlierstageofdevelopment. Whatare microbicides? for HIVprevention.ForPrEP,the ARVsaretakenintablet formandthedrugspreadsthroughoutthebody.Inthecase Intermsof HIVprevention,amicrobicideisaproduct ofamicrobicide,the ARVisappliedtothevaginaorrectum whichisdesignedtobeappliedtothevaginaortherectum, andshouldonlyspreadthroughlocaltissues. inordertoreducetheuser’sriskof HIVinfectionwhen hIVexposureoccurs. Beforethedevelopmentof ARVmicrobicides,researchers hadinvestigatedawidevarietyofsubstanceswithvarying Whilepotentialmicrobicideshavemostoftenbeen modesofaction.Forexample,somesubstancesinterfered developedasgelsorcreams(similartoalubricant),they withtheabilityof HIVtobindontothereceptorsofcells; couldbedevelopedinanumberofdifferentformulations. otherscreatedanenvironmenttoohostilefor HIVtosurvive Forexample,workiscurrentlyunderwayonmicrobicidesin in;othersboostedthevagina’snaturaldefences. However theformof: thesesubstances(eg.Carraguard,BufferGel,Pro2000)turned • vaginalringswhichslowlyreleasetheproduct(similar outtobeineffectiveandforanumberofyears,theresultsof devicesareusedforhormonalcontraception); microbicidetrialswereconsistentlydisappointing. tabletsorpiecesoffilmwhichareplacedinthevagina • InJuly2010,thefirstlargetrialofamicrobicidecontaining orrectum,wheretheydissolveandcoverthemucosal ananti-retroviraldrug(tenofovir)foundthatitreduced surface; women’sriskof HIVinfectionby39%.(Formore analdouchesorenemas; • information,seeWhat research has been conducted into acoatingforacondom. • vaginal microbicides?below). Ineachcase,theproductisappliedtoaspecific,localised partofthebody–thisissometimesreferredtoas‘topical the potEntIal benEFIts of application’. microbicides themostpromisingmicrobicideproductsareall thenumberofnew HIVinfectionsanddiagnoseseachyear formulationsofanti-retroviral(aRV)drugs. Theideaisthat –bothinmenwhohavesexwithmenandinothergroups an ARVappliedinthevaginaorrectummightbeableto –demonstratethatthecurrentprovisionofcondomsand block HIVactivityatthesiteofexposure,thereby ofbehaviourchangeinterventionstosupporttheiruseis preventinginfection.Different ARVsworkindifferentways: insufficienttopreventthe HIVepidemicfromcontinuing. • targetingthevirusandpreventingitfromattachingand Condomsrelyonthewillingnessofbothpartnerstouse enteringwhitebloodcells(thecellsthat HIVmustinfect themandadegreeofnegotiationskillsonthepartofeither inordertoreproduce); partnertoensuretheyareused.Condomshavetobeput • blockingentrybytargetingreceptorsontheoutsideof onwhensexhappens(makingadherencetotheiruse thewhitebloodcellitself; difficult)andtheycanfail,areintrusiveandoftenunpopular. preventing HIVfrommakingmorecopiesofitself • Existing HIVpreventionmethodshavelimitationsanda (replicating)onceithasenteredawhitebloodcell. widervarietyofmethodswouldbewelcometomany theuseof ARVsmeansthatthereareimportantsimilarities people. Alternativemethodswhicharecheap,long-lasting, betweenpre-exposureprophylaxis(PrEP)andmicrobicides withoutside-effects,discreet,controlledbythereceptive MICROBICIDESThis is an interactive PDF with clickable links. Download an online version at www.sigmaresearch.org.uk 1 MaKIng itCOUnt Making it Countisthestrategicplanningframeworkthatguides HIVpreventionforMSMacrosstheCHAPSpartnership. althoughearliereditionsofMaking it Countarguedthatthegovernment,researchersand HIVorganisationsshould takeactiontoencouragethedevelopmentofmicrobicides(andvaccines),thetopicdoesnotfigureinthefourth editionoftheframeworkwhichismuchmoreconcernedwithcurrentdirectcontactinterventionsforgaymenand otherMSM. however,theChaPSpartnershipremainscommittedtopolicyandadvocacyworktoensurethatthedevelopmentof rectalmicrobicidesisapriorityforgovernments,researchersandtheirfunders,and HIVorganisations.Futureeditions ofMiCwilladdresstheissueofmicrobicides,asandwhentheybecomeamoretangiblepossibleintervention. partner,easytoadhereto,andnotrequiringsubstantial movementsuchassexualintercourseorwalking. attentionatthetimeofsex(similartomostcontraceptives) Itneedstocrosstheprotectivebarriersofthevaginaor wouldbeparticularlywelcome. rectum,andpenetratethesurroundingtissueandnearby howevernosingle HIVpreventionsolutionislikelytobe lymphnodes.Butideallyitwouldnotbeabsorbedintothe sufficientonitsown. Anapproachof‘combination bloodstreamandthroughoutthebody–asthiscouldlead prevention’ismorelikelytobeeffective. Thisrequires tomoresideeffects. biomedicalinterventions(suchascondomsormicrobicides) Ifan ARV-basedmicrobicidewereusedbyapersonwith tobeprovidedalongside:behaviourchangeprogrammesto undiagnosed HIV-infection,thereisatheoreticalpossibility supporttheirconsistentuse;treatmentof HIVandsexually thatthiscouldleadtothedevelopmentofdrug-resistant transmittedinfections;andsocialjusticeandhumanrights. hIVandlimitfuturetreatmentoptions. Anideal ARV-based microbicidewoulduseadrugwhichisnotalreadyusedfor Why do we need rectal hIVtreatment. Nonetheless,thereislessriskofresistance microbicides? whenonlyalimitedamountofthedrugisabsorbedinto themainfocusofmicrobicidedevelopmentisonvaginal thebloodstream–oneadvantageofatopicalmicrobicide microbicides,whichareseenbywomen’shealthadvocates overoralpre-exposureprophylaxis. asfemale-controlledpreventionmethodswhichrespondto tobeacceptabletousers,amicrobicideneedstobeeasy therealityofpowerinequalitiesbetweenmenandwomen toapply,unobtrusivetoboththepersonusingitanda aswellastohighinfectionratesamongwomeninmany sexualpartner,andfitwithsexualpreferences(somepeople partsoftheworld. findextralubricationpleasurable,othersdonot). Butthereispressuretooforthedevelopmentofrectal Mostresearchhasinvestigatedproductsthatareapplieda microbicides. HIVistransmittedabouttentimesmoreeasily fewhoursbeforesexandthenagainsometimeafterwards. rectallyasvaginally,withreceptiveanalintercoursebeingthe amicrobicidewhichisappliedeachday,ratherthanwhen mainrouteofinfectionformenwhohavesexwithmen sexisanticipated,mightbeeasierforsomepeopletouse (MSM).MSMhaveadisproportionateburdenof HIV consistently. infection,notonlyintheUK’s‘concentrated’epidemic,but inmany‘generalised’epidemicsinsub-Saharan Africaand Somewomenwouldpreferadual-actingproductthatcan theCaribbean. protectagainstpregnancyand HIVatthesametime.Other womenhaveaneedforavaginalmicrobicidethatwill What’smore,althoughanalintercourseisoftenataboo protectthemfrom HIVbutstillallowconception.Whilean topicforheterosexuals,thereisevidencethatasignificant idealproductwouldbecheaptoproduce,requireno proportionofheterosexualmenandwomenpracticeit.For prescriptionandbeprotectiveagainstothersexually example,inalargesurveyofSouth Africanyoungpeople, transmittedinfections,thismaynotbethecasefor 5.3%ofsexuallyexperiencedwomenand5.5%ofsexually aRV-containingmicrobicides. experiencedmenreportedhavinganalintercourse. Onebarriertothedevelopmentofmicrobicideshasbeen WhataREthe challEnges of limitedinvestmentinresearch.Mostofthefundinghascome DEVElOPIng microbicides? from AmericanandEuropeangovernments,while pharmaceuticalcompanies–normallytheenginesofnewdrug anymicrobicideshouldnotirritateorharmthetissueit research–haveinvestedlittle.Microbicides(especiallyrectal comesintocontactwith,shouldquicklyspreadthroughout microbicides)arethoughtunlikelytogeneratelargeprofits. theareacontainingcellsvulnerableto HIVinfectionand shouldstayinplaceforlongenoughinthefaceof InternationalRectalMicrobicide AdvocatesandtheGlobal MICROBICIDES 2 CampaignforMicrobicidesaretwoorganisationsadvocating consistentmicrobicideusemaybeaschallengingas formoreresearchandinvestmentinmicrobicides. They consistentcondomuse. wouldlikemoreandmorepeopletosupportandget thisstudyisextremelyencouraging,butneedstohaveits involvedintheiractivities. resultsconfirmedbyfurtherstudies. AnotherSouth African study,knownasVOICE,islikelytoreportresultsin2011.It WhataREthe challEnges of iscomparing HIVinfectionratesinwomenusingatenofovir DEVElOPIng rectal microbicides? microbicide,pre-exposureprophylaxisandaplacebo. therearespecificchallengeswhichfacethedevelopmentof athirdefficacytrialiscalledIPM009andwillproduce arectalmicrobicide. resultsin2015. Thistrialwilltesttheeffectivenessof theliningoftherectumismoredelicatethanthatofthe dapivirine(anon-nucleosidereversetranscriptaseinhibitor), vagina.Breachesoftherectalmembrane,whichincreasethe eitherasagelorasavaginalring. chanceof HIVinfection,aremorelikely. Thismeansarectal Inaddition,manymorepreliminarystudies(forexample,in microbicidemayneedtoofferagreaterprotectiveeffect animalsortotestsafetyinhumans)areunderway. Atleast thanoneusedvaginally. 13different ARV-basedmicrobicideshavedemonstrated Whereasthevaginaisasmall,enclosedcavity,therectumis efficacyinblocking HIVinfectioninmonkeys.Someofthese larger.Semencantravelupto60cmalongthegutafteranal aRVsarealsousedfor HIVtreatment,whileotherssuchas intercourse,presentingachallengetothosecreatinga dapivirinehaveanti-hIVactivitybutarenotlicensedfor HIV substancethatwillreachthatfarandstaythere. treatment. Moreofamicrobicidalproductmightbeneededforrectal Itispossiblethatamicrobicidecontainingmorethanone use.Itmaybethatanenema-basedproductmaybethebest aRVwouldbemoreeffectivethanonecontainingasingle wayofensuringtherequiredcoverage.