Undiagnosed HIV Infection and Couple HIV Discordance A - PDF document

UndiagnosedHIVInfectionandCoupleHIVDiscordance AmongHouseholdMembersofHIV-InfectedPeople ReceivingAntiretroviralTherapyinUganda WillyA.Were,MBChB,MPH,*JonathanH.Mermin,MDMPH,*NafunaWamai,MBChB,MPH,* AnnaC.Awor,MSc,*StevensBechange,BSc,*SusanMoss,MPH,*PeterSolberg,MD, Þ RobertG.Downing,PhD,*AlexCoutinho,MBChB,MSc, þ andRebeccaE.Bunnell,PhDMed* Introduction: SystematiceffortstoidentifyHIV-infectedmembers andHIV-discordantcouplesinhouseholdsofindividualstaking antiretroviraltherapy(ART)co uldtheoreticallyreduceHIV transmissionandimproveARTadherence. Methods: WeenrolledHIV-infectedclientsofanAIDSsupport organizationinarandomizedevaluationofdifferentARTmonitor- ingregimensthatofferedhome-basedARTcaretothemandtheir clinicallyeligiblehouseholdmembers.Atbaseline,counselors visitedparticipants’homesandofferedvoluntarycounselingand testing(VCT)toallhouseholdmembers.Weassesseduptake,HIV prevalence,HIVdiscordance,andrateofARTeligibility. Results: Ofthe2373householdmembers,2348(99%)accepted VCT.HIVprevalenceamonghouseholdmemberswas7.5%and variedbyagewith9.5%amongchildrenaged0to5years,2.9% amongpersonsaged6to24years,and37.1%amongadultsaged25 to44years.OfthehouseholdmemberswithHIV,74%hadnever beenpreviouslytested,and39%ofthesewereclinicallyeligible forART.Ofthe120spousesofARTpatientsthatweretested forHIV,52(43%)wereHIVnegative,andofthese,99%hadnot beenpreviouslytested. Conclusions: Provisionofhome-basedVCTtohouseholdmembers ofpeopleinitiatingARTwaswellacceptedandresultedinthe detectionofalargenumberofpreviouslyundiagnosedHIV infectionsandHIV-discordantrelationships. KeyWords: HIV,prevalence,familymembers,voluntary counselingandtesting,antiretroviraltherapy,Uganda ( JAcquirImmuneDeficSyndr 2006;43:91 Y 95) B othHIV/AIDScareandantiretroviraltherapy(ART)are rapidlyexpandinginAfricaandotherresource-limited settings. 1 Mostcareandtreatmentprogramsareclinic-based andutilizeanindividualapproachtoHIVcareandtreatment. However,theburdenofHIVinfectioninhouseholdsof peoplelivingwithHIVmaybehigh. 2 Y 4 Inaddition,HIV discordanceiscommonwithincouplesinAfrica,ranging from3%to20%inthegeneralpopulation 5 Y 7 and30%to51% withincouplesinwhichonepartnerseeksHIVcareser- vices. 2,8 However,knowledgeofpartner’sHIVstatusis extremelylow. 9 SystematiceffortstoidentifyHIV-infected membersandHIV-discordantcouplesinhouseholdsof individualstakingARTcouldtheoreticallyreduceHIV transmissionanddrugsharingpressures,improveART adherence,andprolongsurvivalforpeoplewithpreviously unrecognizedHIVinfection. InastudyinruralUganda,weofferedhome-basedHIV voluntarycounselingandtesting(VCT)tohousehold membersofpeopleinitiatingART.Weassessedacceptance ofhome-basedVCT,HIVprevalence,theproportionof householdmemberswithunrecognizedHIVinfection,the proportionofART-eligiblehouseholdmembers,andthe proportionofHIVdiscordantcouples. METHODS BetweenMay2003andDecember2004,weenrolled HIV-infectedadultsaged18yearsandolder(indexpartici- pants)intheHome-BasedAIDSCareproject,arandomized evaluationofdifferentARTmonitoringregimensforpersons receivinghome-basedARTcare.Participantswererecruited fromTheAIDSSupportOrganization,anongovernmental organizationinTororoandBusiaDistricts,Uganda.After writteninformedconsentwasprovidedbytheparticipants,a venousbloodsamplewascollectedforconrmationofHIV infectionandCD4cellcountenumeration,andaphysical examinationandmedicalhistorywereconductedforclinical E PIDEMIOLOGYAND S OCIAL S CIENCE JAcquirImmuneDeficSyndr & Volume43,Number1,September2006 91 ReceivedforpublicationDecember12,2005;acceptedApril17,2006. Fromthe*CDC-Uganda,GlobalAIDSProgram,NationalCenterforHIV, STDandTBPrevention,CentersforDiseaseControlandPrevention, Entebbe,Uganda;  UniversityofCalifornia,SanFrancisco;and ‚ The AIDSSupportOrganization,Kampala,Uganda. Funding/Support:TheUSDepartmentofHealthandHumanServices/ CentersforDiseaseControlandPreventionprovidedintramuralfundsto supportthestudy,andstaffwereinvolvedinthestudydesign,data collection,analysis,andwritingthemanuscript. Authorcontributions:WillyA.Werewasthemainauthorofthepaper.Peter Solberg,JonathanMermin,andRebeccaBunnell,theprincipal investigators,wrotetheprotocol,supervisedthestudy,guideddata analysis,andhadfullaccesstoallthedataandtakeresponsibilityforthe integrityofthedataandaccuracyofdataanalysis.StevensBechangeand SusanMosssuperviseddataentryandcleaningand,withAnnAwor, analyzeddataandconductedstatisticalanalyses.RobertDowning supervisedandconductedlaboratorytesting.WillyWereandNafuna Wamaisupervisedthestudy.RebeccaBunnellprovidedguidanceto studystaffonbehavioralaspectsofthestudyandassistedininterpreting results.AlexCoutinhohelpeddesignandconductthestudy,andensured theprotocolwasapplicabletoTheAIDSSupportOrganization. Conflictofintereststatement:Noneoftheauthorshadanyconflictsofinterest. Reprints:WillyA.Were,MBChB,MPH,CDC-Uganda,UgandaVirusResearch Institute,P.O.Box49,Entebbe,Uganda(e-mail:wgw7@ug.cdc.gov). Cop yr ight © Lippincott Williams & Wilkins . Unauthor iz ed reproduction of this ar ticle is prohibited. staging.IffoundeligibleforART,theindexparticipants providedwritteninformedconsentforstudystafftovisittheir homestorequestfortheconsentoftheirhouseholdmembers forVCT.Ahouseholdwasdenedaspersonswhosharedfood cookedatacommonhearthandsleptinthesamehouseor clusterofhousesforatleast5daysinaweekforthepreceding 3months.Consentinghouseholdmembersprovidedanger sticksampleofbloodonlterpaperforHIVtesting.Results werereturnedafter2weekstoindividualsorcouplesathome oratthestudyclinic,dependingonparticipants’preference. Allparticipantscouldrequestforfollow-upcounselingand support,includingcounselor-assisteddisclosureifdesired. Forparticipantsaged10to17years,VCTcounseling includedboththechildandparentorlegalguardian;consent wasrequiredfromtheparentorguardian,andassentwas requiredfromthechild.Forchildrenaged0to9years,only theparentorlegalguardianprovidedconsent.Neither consentforHIVtestingnorreceivingtestresultswasrequired forhouseholdmemberstoreceivefreeclinicalcarethatwas partofthestudy.TheVCTwasvoluntaryandcondential. Wecollectedstandardizedinformationabouttestinghistory and,forrst-timetesters,previousbarrierstotesting.HIV- infectedhouseholdmemberswereofferedcotrimoxazole prophylaxis(unlessmedicallycontraindicated),sexualrisk reductioncounselingforadults,andaccesstocareatthestudy clinic;thosefoundtobeeligiblebyCD4of250cells/ K Lor lessorsymptomaticAIDSwereofferedstandardART,most oftenconsistingoflamivudine,stavudine,andeithernevira- pineorefavirenz. Counselorsencouragedco uplestoreceiveresults togetherand,whereHIVdiscordancewasrecognized,offered enhancedcouplecounseling,focusingonunderstanding discordance,makingpersonalizedcoupleriskreduction plans,andcopingwithchallengesandsocialpressuresaround childbearing. PlasmawasscreenedforHIVinfectionusing2 enzyme-linkedimmunoassays(EIA)inparallel(Recombigen HIV-1/HIV-2;TrinityBiotech,Dublin,IrelandandMurex HIV120;AbbotDiagnostics,Chicago,IL).Specimensnega- tiveonbothEIAscreeningtestswereconsiderednegative; specimenspositiveonbothassayswereconsideredpositive. SpecimenswithdiscordantresultswereretestedbyWestern Blot(LAVBlot;Biorad,Richmond,CA).HIVtestingof driedbloodspotsconsistedofascreeningEIA(Virinostika HIV;BioMerieux,Durham,NC)andaconrmationof reactivespecimensbyWesternBlot.HIV-reactivespecimens fromchildrenyoungerthan24monthsweretestedforHIV usingtheRocheCobasr1.5(Roche,Rariton,NJ)assay. Althoughallhouseholdmemberswereofferedthe opportunitytohaveanHIVtest,onlyhouseholdmembers whohadnotreceivedhome-basedVCTinapreviousstudy 10 wereincludedinthisanalysis.Indexparticipantswere categorizedasmarriediftheywerelegallymarriedor cohabitingwithapartneratthetimeofenrollmentinthe study.Iftheyhadnevermarriedorcohabitedorhaddivorced orwerewidowed,theywereclassiedasunmarried.Children werecategorizedintheagegroupsof0to5,6to10,and11to 17years.Dataweredouble-enteredinEpi-Info2000(CDC, Atlanta,GA)andanalyzedusingSASversion9.1(SAS Institute,Cary,NC).Frequencydistributionswereusedto computetheproportionofclientswhoacceptedtesting,HIV prevalence,andtheproportioneligibleforART. ThestudywasapprovedbytheScienceandEthics CommitteeoftheUgandaVirusResearchInstitute,the UgandaNationalCouncilofScienceandTechnology,the InstitutionalReviewBoardsoftheCentersforDisease ControlandPrevention,andtheUniversityofCalifornia, SanFrancisco. RESULTS WeofferedVCTto2373householdmembersof730 indexclients.Themedianageofhouseholdmemberswas 12years(interquartilerange,7 Y 17years),and52%were female.Overall,2348(99% )acceptedVCT;99%ofthem weretestedintheirhome.HIVprevalencewas7.5% amongallhouseholdmembersandvariedbyage.Among childrenaged0to5years,9 .5%wereinfected;among personsaged6to24years,2.9%wereinfected.Among adultsaged25to44years,37.1%wereinfected(Table1). HIVprevalenceamongpeoplelivinginhouseholdsdidnot varybysexoftheindexparticipants(Table2).Among childrenwhosemothershaddiedorwereHIVpositive,HIV prevalencewas17.7%forthoseaged0to5years,5.2%for thoseaged6to10years,and1.7%forthoseaged11to17 years(Table3).Ofthe238whosemotherswereHIV negative,only1childwasHIVinfected.Overall,95%ofthe householdmembershadneverbeenpreviouslytestedfor HIV.Only1ofthe1575childrenaged14yearsandyounger hadbeenpreviouslytested.Previousbarrierstotesting among657(85%)ofthe773householdmembersolderthan 15yearswhohadneverbeentestedincludednoperceived riskofinfection(52%),distancefromtestingsites(8%),and fearofknowingone’sHIVstatus(17%).Lessthan1%listed lackofaccesstoantiretroviral(ARV)careasabarrierto HIVtesting. Ofthe176(7.5%)householdmembersdiagnosedwith HIVinfection,130(74%)hadneverbeenpreviouslytested forHIV.Noneofthe76childrenwithHIVinfectionhadbeen previouslytested.AllhouseholdmemberswhotestedHIV positiveandall52HIV-infectedhouseholdmembers(30%) whowereclinicallyeligibleforART-initiatedtreatment receivedcotrimoxazoleprophylaxis.Ofthe397spouses livinginthehouseholds,268(68%)hadneverbeentestedfor HIV.Ofthe120spousesofpatientsonARTtested,52(43%) wereHIVnegative(Table2),andofthese,99%hadnotbeen previouslytested. DISCUSSION Ninety-ninepercentofthehouseholdmembersof peoplewithHIVtakingARTacceptedVCT,andalmost allweretestedintheirhomes.Theprevalenceof previouslyundiagnosedHIVinfectionwashigh,particu- larlyamongadultsandyoungchildren.Over70%ofHIV infectionsamonghouseholdmemberswerediagnosedfor thersttimethroughhome-basedprovisionofHIV counselingandtesting.HIVdiscordancewithincouples Wereetal JAcquirImmuneDeficSyndr & Volume43,Number1,September2006 92 Cop yr ight © Lippincott Williams & Wilkins . Unauthor iz ed reproduction of this ar ticle is prohibited. washigh:43%ofspousesofHIV-infectedindexparticipants wereHIVnegative. HIVprevalenceamongadultsaged15to44years withinhouseholdsofHIV-infectedpatientswasmorethan 3timesthatfoundinarecentnationalHIVprevalence surveyinUganda, 11 highlightingtheimportanceof targetingfamilymembersofHIV-infectedpeoplefor VCTeveninacountrywithhighprevalenceofHIVinthe generalpopulation.Theoretically,VCTcanbeprovided withinclinicsorathome,althoughuptakeseemstobemuch higherduringhomevisits.Forexample,experiencein facility-basedPreventionofMother-to-ChildTransmission TABLE2. HIVPrevalenceAmongAdultsandChildreninHouseholdsofPeopleWithHIVReceivingARTinTororo andBusiaDistricts,Uganda(2004) HouseholdMembers WomenIndexParticipants inHousehold MenIndexParticipants inHousehold Overall Total UnmarriedMarriedOverallWomenUnmarriedMarriedOverallMen Adults Spousesofindexparticipants61.8(21/34)54.7(47/86)56.7(68/120) Otheradults7.2(16/221)2.1(1/47)6.3(17/268)1.7(1/59)11.9(7/59)6.7(8/119)6.5(25/386) Children,y e 58.6(17/198)12.9(11/85)9.9(28/283)5.7(2/35)11.8(14/119)10.1(16/159)9.9(44/442) 6 Y 103.6(9/253)5.5(6/110)4.1(15/363)0.0(0/5)4.6(7/153)3.4(7/204)3.9(22/566) 11 Y 172.4(9/382)0.9(1/114)2.0(10/496)2.0(1/49)0.7(1/137)1.1(2/188)1.8(12/682) G 184.2(35/833)5.8(18/309)4.6(53/1142)2.2(3/134)5.4(22/407)4.5(25/551)4.6(78/1685) TABLE1. VoluntaryCounselingandTesting,HIVPrevalence,andARVEligibilityAmongHouseholdMembersinTororo andBusiaDistricts,Uganda(2004) AgeinYears VCTAcceptance, %(n/Total OfferedTesting) OverallHIV PrevalenceAmong VCTAcceptors,% (95%CI) HIVPrevalence AmongFirst-time Testers,n/Total=% (95%CI) ARVEligibility AmongFirst-time Testers,% (n/Total) OverallARV Eligibility,% (n/Total) 0 Y 5 F98.8(248/251)9.7(6.0 Y 13.4)24/248=9.7(6.0 Y 13.4)30.4(7/23)30.4(7/23) M99.1(215/217)9.3(5.4 Y 13.2)20/215=9.3(5.4 Y 13.3)55.0(11/20)55.0(11/20) 6 Y 10 F99.7(287/288)3.5(1.4 Y 5.6)10/287=3.5(1.4 Y 5.6)44.4(4/9)44.4(4/9) M99.7(315/316)4.1(1.9 Y 6.3)13/315=4.1(1.9 Y 6.3)53.9(7/13)53.9(7/13) 11 Y 17 F99.7(356/357)1.7(0.4 Y 3.0)6/356=1.7(0.4 Y 3.0)66.7(4/6)66.7(4/6) M99.5(378/380)1.6(0.3 Y 2.9)6/378=1.6(0.3 Y 2.9)33.3(2/6)33.3(2/6) G 17 F99.4(891/896)4.5(3.1 Y 5.9)40/891=4.5(3.1 Y 5.9)39.5(15/38)39.5(15/38) M99.5(908/913)4.3(3.0 Y 5.6)39/908=4.3(3.0 Y 5.6)51.3(20/39)51.3(20/39) Overallchildren99.5(1799/1809)4.4(3.4 Y 5.3)79/1799=4.4(3.4 Y 5.3)45.5(35/77)45.5(35/77) 18 Y 24 F95.7(67/70)9.0(2.1 Y 15.8)4/60=6.7(0.4 Y 13.0)25.0(1/4)16.7(1/6) M98.9(93/94)2.2(0.0 Y 5.1)2/87=2.3(0.0 Y 5.4)50.0(1/2)50.0(1/2) 25 Y 34 F93.9(61/65)29.5(18.1 Y 41.0)7/35=20(6.8 Y 33.3)28.6(2/7)33.3(6/18) M100.0(40/40)33.3(18.5 Y 48.1)7/26=26.9(9.9 Y 44.0)42.9(3/7)50.0(6/12) 35 Y 44 F95.8(69/72)37.7(26.3 Y 49.1)14/44=31.8(18.1 Y 45.6)14.3(2/14)26.9(7/26) M92.6(25/27)60.0(40.8 Y 79.2)7/11=63.4(35.2 Y 92.6)28.6(2/7)33.3(5/15) 45+ F99.2(130/131)3.1(0.1 Y 6.1)3/118=2.5(0.0 Y 5.4)66.7(2/3)50.0(2/4) M98.5(64/65)20.3(10.5 Y 30.2)7/52=13.5(4.2 Y 22.7)57.1(4/7)46.2(6/13) Overalladults F98.7(1218/1234)7.7(6.2 Y 9.2)68/1148=5.9(4.6 Y 7.3)33.3(22/66)33.7(31/92) M99.2(1130/1139)7.3(5.8 Y 8.8)62/1083=5.7(4.3 Y 7.1)48.4(30/62)46.9(38/81) CIindicatescondenceinterval. JAcquirImmuneDeficSyndr & Volume43,Number1,September2006 UndiagnosedHIVInfection, CoupleHIVDiscordance,andART 93 Cop yr ight © Lippincott Williams & Wilkins . Unauthor iz ed reproduction of this ar ticle is prohibited. programshasshownthatonlybetween3%and15%ofthe partnersreceivedtesting. 12 Twogeneralpopulationstudiesin Ugandashowed2-to4-foldincreasesinreceiptofHIVtest resultswhenprovidedtoparticipantsintheirhomesrather thanthroughanearbyclinic. 13 Y 16 Thehighrateof acceptanceofVCTamongfamilymembersofpeoplewith HIVinthepresentstudydoesnotseemtobecausedbythe availabilityofART.UptakeofVCTwasmorethan97%in apreviousstudyofmorethan3000householdmembers ofpeoplewithHIVinwhichnoARTwasoffered toparticipantsinthesamearea. 13 InUganda,likeelsewhereinsub-SaharanAfrica,most HIVcareprogramsincludemainlyadultclients.Yet, approximately2.5millionchildreninAfricahaveHIV, 17 andwithouteffectivecare,almosthalfwilldiebeforetheir thirdbirthday. 18 Inthisstudy,becauseofahousehold approachtoHIVtesting,weidentiedmanychildrenwith HIVinfection V halfofwhomneededandwereprovided ARTatthetimeoftesting.Only1ofthe238childrenwhose motherswereHIVnegativehadHIV,but6%ofthechildren withHIV-infectedordeceasedmotherswereinfectedwith HIV.Prevalencewasveryhigh,nearly18%,amongthose agedyoungerthan5yearsbutwasalsohighforolderchildren ofHIV-infectedanddeceasedmothers.Itwouldlikelybe mostcost-effectivetolimitchildVCTtoallchildrenwhose mothersdiedorwhoareHIVinfected. Theimplementationofhome-basedVCTisopera- tionallyfeasibleinruralUganda.Atthetimeofenrollmentin thisstudy,weconductedlaboratorytestinginthestudy laboratoryandmadeareturnvisittohomesforresults counseling.However,atTheAIDSSupportOrganization centersandseveralcommunity-basedprograms,trainedlay providersarenowconductingrapidngersticktestingin clienthomes,andthisissupportedbythenewUgandan MinistryofHealthcounselingandtestingguidelines. 19 Over 200,000individualsinvariouscommunitiesofUgandahave receivedVCTintheirhomes.Driedbloodspotsareroutinely collectedforqualitycontrolusingaparallelEIAtesting algorithm(VirinostikaUniformIIplus0andMurexHIV 120).Cost-utilityanalyseswillbeimportanttohelpcompare thepotentialbenetsofahome-basedapproach,including coverage,disclosure,andcouplescounselingwithmore traditionalfacility-basedandreferralapproaches. Itwouldbeusefultoevaluatethistypeofintervention inurbansettingswhereacceptancemaybedifferent.Concern hasbeenraisedaboutpossiblenegativesocialconsequences thatmayoccurwithpartnerVCT, 20,21 butinfollow-up studiesofthepopulationinthisstudy,wefoundsubstantial increasesinpositivesocialeventssuchasstrengthened relationshipsandcommunitysupportandnoincreasein negativeeventsduringthe3monthsafterhome-basedVCT ascomparedwith3monthsbeforeenrollment. 22 Ourhigh acceptancerateswereinthecontextofprovisionofARTand maynotbeapplicabletoothersettings.However,similarly, acceptancerateshavebeendemonstratedinthissame populationandseveralotherhome-basedVCTprogramsin UgandaevenbeforetheavailabilityofART. 10,13 ProvisionofVCTforfamilymembersofpeopleinHIV careandtreatmentprogramsisanimportantinterventionfor bothcasendingandforpreventionofHIVtransmission. ProvidingcoupleswithHIVtestingandcounselingdecreases high-risksexualbehaviorandHIVtransmission, 23,24 partic- ularlyamongHIV-discordantcouples. 25 Y 27 Manypersons withHIVbelievethattheirpartnersarealreadyinfectedand thereforedonotavoidhigh-riskpractices;however,inour study,43%ofthespousesofHIV-infectedmarried participantswereHIVnegative.ReductionofHIVtransmis- sionwithinHIV-discordantcouplesshouldalsohelpcontrol thespreadofARV-resistantvirusfrompersonstakingARVs. IntegrationoffamilyVCTasaroutinepartofHIVcareand treatmentprogramswillbenecessaryforpublichealthefforts tocontroltheHIVepidemicandsupportpeoplewithHIVto livelongerandhealthierlives. ACKNOWLEDGMENTS WethankTororoHospitaladministrativeandclinical staff;thevolunteers,staff,andclientsofTheAIDSSupport Organization;theUSEmbassyinKampala;GAPheadquar- ters;andstaffofCDC-Uganda,includingtheinformatics, clinical,laboratory,andadministrativeunitsofCDC-Tororo. 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