AUSTRALIAN)HIV)OBSERVATIONAL)DATABASE)))))))))))))) ANNUAL)REPORT)

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1 AUSTRALIANHIVOBSERVATIONALDATABASE ANNUALREPORT (Volume12,Number1:August2012 CD4cellresponsestocombinationantiretroviraltherapyinpatients startingtherapyathighcd4cellcounts Background:Manystudieshaveshownthebenefitofcombinationantiretroviraltherapy(cARTtosuppressviral replicationinpatientswithlowcd4cellcounts,whichinturnallowsanindividual simmunesystemtorecover andprotectagainstaidsanddeath.however,minimaldatahasbeenpublishedontheeffectofcartonpersons whocommencetreatmentathighercd4cellcountlevels.weexaminedcd4cellresponsestocombination antiretroviraltherapy(cartinpatientsenrolledintheaustralianhivobservationaldatabase(ahodwho commencedcartatcd4cellcounts>350cells/µl. Methods:RetrospectiveandprospectivedatawereexaminedfromHIVpositiveadultsfromAHODwhohad commencedcartafter1 st January1997withnopriorantiretroviraltherapy,andhadabaselineCD4count>350 cells/µl.assuming intentionwtowtreat principles,cd4responseswerecomparedaccordingtoinitialbaseline CD4countsandweremodelledusingrandomWeffects,repeatedWmeasurementmodels.Modelswereadjustedfor age,gender,baselinehivwrna,recentseroconversionandcalendaryear.usingpublishedaidsand/ordeath incidenceratescombinedwiththedatasummarisedbytimeandpredictedcd4cellcount,wecalculatedthe expectedabsoluteandrelativereductioninriskofaneventfordifferentstartingbaselinecd4strata. Results:Ofthe3,173AHODpatientsrecruited,432wereeligiblefortheanalysis.Atotalof4,057CD4 measurementswereobservedoveracombinedtotalof1957patientyears.cd4cellresponsewaslargely predictedbytimesincecommencementofcart,baselinecd4andtheirinteraction.theproportionofpatients whosecd4countswereabove500cells/µlat12months(bybaselinecd4strata351w500,501w650and650+ cells/µlrespectivelywas64,84,93andby72monthswas70,69,73[figure1].meancd4counts increasedabove500cells/µlinallbaselinecd4strataby12months(meansof596,717and881cells/μlin baselinecd4strata351w500,501w650and>650cells/µlrespectively.after72monthssinceinitiatingcart, meancd4cellcounts(byincreasingbaselinecd4stratawere689,746,742cells/μl[figure2].theexpected relativereductioninriskofaidsormortalityforbaselinecd4countgroup>650cells/µlrelativeto351w500 cells/µlgroupwasapproximately14,oranabsoluteriskreductionof1.25per1000treatedpatientyears [Table1]. Table1:Cummulativeproportionoftime(patientSyearspredictedforCD4strataoverfollowSup(72months andtheestimatedabsoluteriskreductionandrelativeriskreductionofaidsand(ordeathincidence. AIDS/Death BaselineCD4 (cells/μl Predicted CD4strata (cells/μl FollowSup( incd4strata Hypothetical PatientYear Split(N=1,000 EstimatedNo. EventsbyCD4 strata TotalEstimate No.Events ARR RRR CD4 BL 351W500 < W CD4 BL 501W650 < W W CD4 BL >650 < W W AHODHIVObservationalDatabaseAnnualReport2012 1

2 Conclusion:PatientsstartingcARTathighCD4cellcounts(>650cells/µLtendtomaintainthisimmunological leveloversixyearsoffollowwup.patientsstartingfrom351w500cd4cells/µlachievelevelsof>650cells/µlafter approximatelythreeyearsofcart.initiatingcartwithabaselinecd4count501w650or>650cells/µlrelativeto 351W500cells/µLindicatedaminimalreductioninriskofAIDSincidenceand/ordeath. Reference:WrightST,CarrA,WoolleyI,GilesM,HoyJ,CooperDA,etal.CD4cellresponsestocombinationantiretroviral therapyinpatientsstartingtherapyathighcd4cellcounts.jacquiredimmunedeficencysyndromes(2011;58: AHODHIVObservationalDatabaseAnnualReport2012 2

3 Table1:AllAHODdemographics 1 (Total 3572 Number ( Number ( Sex CD4(cells/μl 1 Male 3336 (93 < (12 Female 228 (6 200W (11 Transgender 8 (0 300W ( (46 Age(years 1 Missing 400 < (10 Mean[SD] 221 [280] 30W (37 40W (33 HIVviralload(copies/ml ( (59 Mean[SD] 42 [10] 401W (18 > (23 Aboriginal/TorresStraitislander 2 Missing 243 Yes 41 (1 Median[LQ UQ] [ ] No 2187 (61 Missing 1344 (38 PriorAIDSdefiningillness 1 Yes 608 (17 Exposurecategory No 2964 (83 Malehomosexualcontact 2616 (73 MalehomosexualcontactandIDU 129 (4 HepatitisCever Injectingdruguser(IDU 74 (2 Yes 384 (11 Heterosexualcontact 367 (10 No 3188 (89 Receiptofblood/bloodproducts 21 (1 Other 307 (9 HepatitisBever Missing 58 (2 Yes 151 (4 No 3421 (96 EstimatedyearofHIVinfection 3 < (0 Totalpatientsunderactivefollowupinlast12months 1985W (3 (N= W ( (21 RecentCD4(cells/μl 6 Missing 2342 (66 < (5 200W (5 Metropolitan/nonSmetropolitanclinic 300W (26 Metropolitan 2945 ( (64 NonWmetropolitan 627 (18 Missing 120 Mean[SD] 624 [293] Regionofbirth AustraliaandNewZealand 1818 (51 RecentHIVviralload(copies/ml 6 AsiaandOceania 157 ( (90 BritainandIreland 120 (3 401W (4 Europe 91 (3 > (6 AfricaandMiddleEast 55 (2 Missing 196 NorthAmerica 27 (1 Median[LQ UQ] [400400] SouthAmerica 28 (1 Missing 1276 (36 1.Age&priorAIDSdefiningillnessattimeofcohortenrolment.CD4count&HIVviralloadclosesttoandwithin3monthsofcohort enrolmentdate. 2.Datanotavailablefor8of28sites 3.YearofHIVinfection=middatebetweendateoffirstpositiveandlastnegativetest(codedasmissingifeitherfirstpositiveorlast negativedatearemissing. 4.LQ=LowerquartileUQ=Upperquartile. 5.MostrecentvisitisbetweenMarch31,2011andMarch31, MostrecentCD4count&HIVviralloadbetweenMarch31,2011andMarch31,2012 AHODHIVObservationalDatabaseAnnualReport2012 3

4 Table2:Followupstatusbycalendaryear Year Enteredstudy Deaths LosttoFollowup Total 3572 CompletefollowSup(percentageofpatients :72 LosstofollowSup(per100personyears:4.15(95CI:3.89S4.43 Mortality(per100personyears:1.27(95CI:1.13S July1WDecember31, January1WMarch31, Patientswhohavediedoranypatientsseenatclinicsitewithinthelast12months(March31,2011WMarch31,2012are consideredtohavecompletefollowwup. AHODHIVObservationalDatabaseAnnualReport2012 4

5 Figure1:ProportionofAIDSandnonSAIDSrelateddeathsinAHODsincecohortenrolmentby year Percent ( Year Non-AIDS related AIDS related dataomittedduetoalownumberofobservations(N=3overtheperiod1January 31March2012. Table3:TotalnumberofdeathsinAHODsincecohortenrolment,byAIDSornonSAIDS relatedclassificationandyear NonWAIDS related AIDS related 1999S All years Unknown Total deaths 1 1January 31March2012 Table4:SummaryofAIDSdefiningillnessandnonSAIDSrelateddeathsreportedsincecohort enrolmentandwithinthelastyear 1 TypeofAIDSdefiningillness N=12 NonSHIVrelateddeaths N=6 HIVencephalopathy 2 Cancer 2 KaposisSarcoma 2 RenalFailure 2 Pneumocystiscarinii/jiroveciipnuemonia 2 CVD 1 HIVwastingsyndrome 2 Suicide 1 Candidiasisofthebronchi,tracheaorlungs 1 Oesophagealcandidiasis 1 Coccidiodomycosis 1 Toxoplasmosis March March2012 AHODHIVObservationalDatabaseAnnualReport2012 5

6 Table&5:&Trends&in&antiretroviral&treatment 1 & 2001& 2002& 2003& 2004& 2005& 2006& 2007& 2008& 2009& 2010& 2011& & Patientsunder activefollowup 1 (N=1563& (N=1718& (N=1790& (N=1906& (N=1887& (N=1892& (N=1915& (N=1893& (N=1756& (N=1907& (N=1829& (N=1520& Treatment& N& ( N& ( N& ( N& ( N& ( N& ( N& ( N& ( N& ( N& ( N& ( N& ( Nevertreatment 181 ( ( ( ( (9 161 (9 154 (8 161 (9 137 (8 128 (7 115 (6 83 (5 Evertreatment N=1382& N=1537& N=1611& N=1723& N=1721& N=1731& N=1761& N=1732& N=1619& N=1779& N=1714& N=1437& Currently ( ( ( ( ( ( ( ( ( ( ( (92 Previously, notcurrently 214 ( ( ( ( ( ( (9 160 (8 108 (6 80 (4 63 (3 36 (2 Number&of&drugs&ever & ( ( ( ( ( ( ( ( ( ( ( (26 4L6 485 ( ( ( ( ( ( ( ( ( ( ( (23 7L9 365 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (31 Number&of&drug&classes&ever 4 & 1 67 (5 65 (4 70 (4 62 (4 47 (3 44 (3 42 (2 35 (2 28 (2 32 (2 45 (3 35 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (39 4 L 14 (1 19 (1 30 (2 42 (2 49 (3 57 (3 63 (4 108 (7 177 ( ( (15 5 L L L L L 5 (0 9 (1 21 (1 34 (2 62 (3 65 (4 56 (4 6 L L L L L L L 1 (0 5 (0 6 (0 7 (0 6 (0 1.Treatmentstatusforallpatientsunderactivefollowuptothe1 Januaryofeachyearisincludedinthisanalysis.Includesprospectivedataonly(i.e.recordspriortoAHODenrolmentareexcluded. 2.1 st JanuaryL31 st March Currentlyontreatmentisdefinedasreceivingtreatmenttothe1 st Januaryofeachyear. 4.Denominatoristhenumberofpatientswhohaveeverreceivedtreatment. AHODHIVObservationalDatabaseAnnualReport2012 6

7 Table&6:&Trends&in&combination&antiretroviral&treatment 1 & 2001& 2002& 2003& 2004& 2005& 2006& 2007& 2008& 2009& 2010& 2011& & Combination 3 & N ( N ( N ( N ( N ( N ( N ( N ( N ( N ( N ( N ( 1 st combination 381 ( ( ( ( ( ( ( ( ( ( ( (26 2 nd combination 283 ( ( ( ( ( ( ( ( ( ( ( (23 3 rd combination 168 ( ( ( ( ( ( ( ( ( ( ( (15 4 th+ combination 174 ( ( ( ( ( ( ( ( ( ( ( (31 1.Patientsareclassifiedaccordingtotheircombinationantiretroviraltherapy(ARTwiththelongestdurationineachcalendaryear.IncludespatientswhocommencedtheirfirstcombinationARTafter January1,1997foratleast14days.ThedenominatorincludesallAHODpatientsthatcouldhavebeenonantiretroviraltreatmentinanycalendaryear(i.e.HIVpositive,whocommencedtheirfirst combinationartafterjanuary1,1997foratleast14days,orwereonlyonmono/dualtherapy,orneverreceivedanytreatment.includesprospectiveandretrospectivedata. 2.31March March Combinationsinclude3ormoreantiretroviraldrugs,doesnotincludemono/dualtherapy.Regimenswithinterruptionsoflessthan7dayswereconsideredascontinuoustreatment. AHODHIVObservationalDatabaseAnnualReport2012 7

8 Table&7:&Immunological&and&virological&trends 1 & 2001& 2002& 2003& 2004& 2005& 2006& 2007& 2008& 2009& 2010& 2011& Viral&load&(copies/ml& Total&N&(with&measure& OffTreatment 2 No.withaviralloadcount Median IQR 4100L L L L L L L L L L L42600 OnTreatment 3 No.withaviralloadcount Median IQR 50L685 50L460 50L399 50L365 50L225 50L50 50L50 50L50 50L50 50L50 50L50 CD4&count&(cells/μl& Total&N&(with&measure& OffTreatment No.withaCD4count Median IQR 370L L L L L L L L L L L681 OnTreatment 3 No.withaCD4count Median IQR 325L L L L L L L L L L L780 1.Includesretrospectiveandprospectivedata.Offtreatmentifneveronaregimenofdurationgreaterthan14daysforgivencalendaryear.Viralloadtakenasmedianvalueduringregimenoflongest durationforgivencalendaryear.undetectableassayleveltakenas 50copies/ml.Datafor2000and2001includes2siteswithminimumassaysensitivityof400copies/ml.Datafor2002includes1site withminimumassaysensitivityof400copies/ml 2.Patientswhohavenotreceivedtreatmentduringthecalendaryear 3.Patientswhohavereceivedanytreatmentduringthecalendaryear 4.Includespatientswithaviralloadmeasuredduringtherelevantcalendaryear. 5.IncludespatientswithaCD4countmeasuredduringtherelevantcalendaryear AHODHIVObservationalDatabaseAnnualReport2012 8

9 Figure2:Proportionofpatientswithanundetectableviralload,bytreatmentstatus(off/on treatmentandyearaccordingtoassaysensitivity 1 undetectable viral load OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON Year 50 copies/ml sensitivity 400 copies/ml sensitivity 1. Offtreatmentifneveronaregimenofdurationgreaterthan14daysforgivencalendaryear.Viralloadtakenas medianvalueduringregimenoflongestdurationforgivencalendaryear.datafor2000and2001includes2sites withminimumassaysensitivityof400copies/ml.datafor2002includes1sitewithminimumassaysensitivityof400 copies/ml Figure3:CD4cellcounts(cells/µlinpatientsreceivingtreatmentbycalendaryear 1E ProproGonofcohort CD4: 750 CD4:500M749 CD4:250M499 CD4:0M249 Missing OffTreatment CalendarYear 1.IncludespatientswithaprospectiveCD4measureduringtherelevantcalendaryear. 2.Forpatientsontreatment,analysisbasedontheinitialtreatmentintent,notontreatmentadministered(ITT,i.e.no adjustmentsaremadeforoffmtreatmentfollowingcartinitiation. 3.Patientsofftreatmentincludethosewhohaveenrolledandhavenotintiatedcombinationantiretroviraltherapy. AHODHIVObservationalDatabaseAnnualReport2012 9

10 Table8:ToptentreatmentcombinationsamongtheAHODcohort 1 :JanuaryEDecember2011 In2011,therewereatotalof397uniqueantiretroviraltreatment(ARTcombinationsamongthe1867 AHODpatientsoncombinationART.Atotalof2115combinationregimenswererecordedamongthese patientsthroughout2011.thetoptenmostcommonartcombinationsaredescribedbelow. ARTcombinations Numberofregimensrecordedduring2011 emtricitabine+efavirenz+tenofovir 364 emtricitabine+nevirapine+tenofovir 161 abacavir+lamivudine+nevirapine 153 emtricitabine+atazanavir+ritonavir+tenofovir 153 emtricitabine+tenofovir+raltegravir 76 abacavir+lamivudine+efavirenz 73 abacavir+lamivudine+atazanavir+ritonavir 52 emtricitabine+kaletra+tenofovir 47 lamivudine+zidovudine+nevirapine 44 emtricitabine+ritonavir+tenofovir 29 1.Includesretrospectiveandprospectivedata.Combinationsinclude3ormoreantiretroviraldrugs.Fixeddosecombinations areseparatedintoindividualcomponentantiretroviraldrugs. AHODHIVObservationalDatabaseAnnualReport

11 Table&9:&& Current&use&of&individual&antiretroviral&treatments 1 & &&&&&&&&&&&&&&2002& &&&&&&&2003& &&&&&2004& &&&&&2005& &&&&&2006& &&&&&2007& &&&&&2008& &&&&&2009& &&&&&2010& &&&&&2011& &&&&& & N ( N ( N ( N ( N ( N ( N ( N ( N ( N ( N ( Nucleoside&analogue&reverse&transcriptase&inhibitors&(RTI& Abacavir 541 ( ( ( ( ( ( ( ( (9 183 (9 118 (8 Combivir ( ( ( ( ( (9 182 (7 147 (6 135 (6 98 (5 66 (4 Didanosine 432 ( ( ( ( (8 123 (5 91 (4 57 (2 46 (2 25 (1 17 (1 Emtricitabine 1 (0 1 (0 1 (0 38 (1 94 (4 63 (2 89 (4 89 (4 102 (4 101 (5 76 (5 Kivexa 3 6 (0 7 (0 15 (1 93 (4 311 ( ( ( ( ( ( (16 Lamivudine 968 ( ( ( ( ( ( ( ( ( ( (10 Stavudine 609 ( ( ( (7 115 (5 71 (3 56 (2 40 (2 28 (1 13 (1 8 (1 Tenofovir 252 ( ( ( ( ( ( ( ( ( ( (13 Trizivir (6 151 (6 144 (6 138 (5 122 (5 87 (3 67 (3 54 (2 41 (2 30 (1 17 (1 Truvada 5 5 (0 7 (0 8 (0 15 (1 363 ( ( ( ( ( ( (30 Zalcitabine 24 (1 15 (1 10 (0 8 (0 5 (0 4 (0 4 (0 3 (0 2 (0 2 (0 2 (0 Zidovudine 292 ( ( ( (8 162 (6 121 (5 97 (4 56 (2 44 (2 25 (1 19 (1 Apricitabine Q NonGnucleoside&analogue&RTI& Q Q 1 (0 1 (0 1 (0 1 (0 1 (0 1 (0 Q Delavirdine 19 (1 18 (1 18 (1 12 (0 12 (0 10 (0 4 (0 3 (0 3 (0 1 (0 1 (0 Efavirenz 383 ( ( ( ( ( ( ( ( ( ( (10 Nevirapine 664 ( ( ( ( ( ( ( ( ( ( (20 Etravirine Q Q Q Q 3 (0 23 (1 47 (2 73 (3 85 (4 83 (4 64 (4 1.Alltreatmentrecordsof 2weeksoftreatmentinanycalendaryearwereincludedinthisanalysis.Thedenominatorincludesallpatientsthatcouldhavebeenonantiretroviraltherapy(i.e.HIVpositiveinanycalendaryear.The proportionofpatientsoneachdruginanycalendaryeardoesnotaddupto100acrossallartdruggroupsineachcalendaryearaspatientsonmorethanonearvduringacalendaryearperiodwillbecountedinallofthe relevantartgroups.includesretrospectiveandprospectivedata. 2.Comibivir Lamivudine&Zidovudine. 3.Kivexa abacavir&lamivudine. 4.TrizivirQabacavir&lamivudine&zidovudine. 5.Truvada tenofovir&emtricitabine; 6.Kaletra lopinavir&ritonavir; 7.Atripla tenofovir&emtricitabine&efavirenz. 8.1 st JanuaryQ31 st March. Q AHODHIVObservationalDatabaseAnnualReport

12 Table&9&continued:& Current&use&of&individual&antiretroviral&treatments 1 & Protease&Inhibitor& &&&&2002& &&&&2003& &&&2004& &&&2005& &&&2006& &&&&2007& &&&&2008& &&&2009& &&&2010& &&&&2011& &&& & N ( N ( N ( N ( N ( N ( N ( N ( N ( N ( N ( Amprenavir 72 (3 61 (2 46 (2 40 (2 31 (1 28 (1 28 (1 29 (1 27 (1 23 (1 15 (1 Atazanavir 4 (0 135 (5 256 ( ( ( ( ( ( ( ( (19 Darunavir Q Q 6 (0 11 (0 40 (2 72 (3 116 (5 157 (7 185 (8 194 (9 146 (9 Fosamprenavir 2 (0 1 (0 2 (0 32 (1 37 (1 33 (1 30 (1 24 (1 16 (1 12 (1 7 (0 Indinavir 249 ( (7 114 (4 63 (2 40 (2 27 (1 19 (1 9 (0 6 (0 4 (0 4 (0 Kaletra ( ( ( ( ( ( ( ( ( ( (9 Nelfinavir 175 (7 127 (5 96 (4 61 (2 41 (2 28 (1 8 (0 6 (0 4 (0 3 (0 1 (0 Ritonavir 350 ( ( ( ( ( ( ( ( ( ( (29 Saquinavir 169 (7 142 (6 121 (5 110 (4 91 (4 74 (3 60 (2 41 (2 31 (1 27 (1 18 (1 Tipranavir 1 (0 11 (0 16 (1 22 (1 18 (1 9 (0 7 (0 5 (0 3 (0 3 (0 0 (0 Fusion&Inhibitor& Enfurvitide 28 (1 45 (2 53 (2 59 (2 64 (3 56 (2 45 (2 35 (1 28 (1 20 (1 13 (1 CCR5& Maraviroc Q Integrase&Inhibitors& Raltegravir Q Class&Combinations& Q Q Q Q 8 (0 7 (0 6 (0 14 (1 21 (1 28 (1 31 (2 24 (2 Q 11 (0 65 (3 173 (7 291 ( ( ( (21 Atripla 7 Q Q Q Q Q Q 1 (0 9 (0 234 ( ( (14 1.Alltreatmentrecordsof 2weeksoftreatmentinanycalendaryearwereincludedinthisanalysis.Thedenominatorincludesallpatientsthatcouldhavebeenonantiretroviraltreatment(i.e.HIVpositiveinanycalendaryear. Theproportionofpatientsoneachdruginanycalendaryeardoesnotaddupto100acrossallARVdruggroupsineachcalendaryearaspatientsonmorethanoneARTduringacalendaryearperiodwillbecountedinallofthe relevantartgroups.includesretrospectiveandprospectivedata. 2.Comibivir Lamivudine&Zidovudine. 3.Kivexa abacavir&lamivudine. 4.TrizivirQabacavir&lamivudine&zidovudine. 5.Truvada tenofovir&emtricitabine. 6.Kaletra lopinavir&ritonavir. 7.Atripla tenofovir&emtricitabine&efavirenz. 8.1 st JanuaryQ31 st March. AHODHIVObservationalDatabaseAnnualReport

13 AHODHIVObservationalDatabaseAnnualReport MONITORING(DISPENSED(ANTIRETROVIRALS(VIA(THE(s100(PROGRAM( Dataonthenumberofpatientswhoweredispensedantiretroviral(ARVdrugsperstateperfinancial yearquarter,reportedinthepublichospitaldispensednationalpatientreportfromtheaustralian Government shighlyspecialiseddrugs(hsd(s100programwereanalysedtogetherwithdataonart usefromtheahodsampletoestimatetotalnumbersofpatientsonartbystateandnationally,by year.atthistime,allarvdrugsinaustraliaarepubliclyfundedthroughthes100programandshould berecordedinthepublichospitaldispensednationalpatientreport.sincepatientswithhivinfection generallyreceivethreeormorearvdrugsincombination,andbecausethes100programonlycollects dataonindividualarvdrugs,itisnotpossibletoenumeratedirectlythenumberofpatientsreceiving ARTfromthes100data. OneofthecommonlyusedARVdrugsfortreatmentofHIVinfectionislamivudine.Yet,itisalsoused forthetreatmentofhepatitisbinfection.asthepbscodeisnotincludedinthepublichospital DispensedNationalPatientReport,itisnotpossibletoseparatethenumberofpatientswhowere dispensedlamivudinetreatmentforhivfromthosereceivinglamivudineforhbv.therefore,we estimatedthenumberofpersonyearsoflamivudine(100mgtabletsforhbvtreatmentfromthepublic HospitalDispensedNationalPackNumberReport,whichincludesthePBScode,dosageandthetotal numbersofpacksdispensedforeachdrugperfinancialquarter.toestimatethetotalnumberof patientsdispensedlamivudineforhivtreatment,wedeductedthetotalnumberofpersonyearsof lamivudinetreatmentforhbveachyearfromthetotalnumberofpatientsdispensedlamivudinefor HIVandHBVtreatment.Thismethodisbasedontheassumptionthatthemajorityofpatientsreceived acompleteyearoftreatmentduringanycalendaryearperiod. ToestimatethenumberofpatientsreceivingART,wecombineddataontheproportionofpatients receivingcertainmutuallyexclusivearvsinahodwithdatafromthes100programonthetotal numberofpeoplereceivingthesamearvs.forexample,lamivudineandemtricitabineareacommon componentofcombinationartregimensinaustralia,butshouldnotbeprescribedincombination.we calculatedtheproportionofalltreatedpatientsinahodwhoreceivedlamivudineoremtricitabineas partofanartregimenbyyearandstate.wealsoestimatedthetotalnumberofpatientsdispensed lamivudineoremtricitabineforhivinfectioneachyearthroughthes100programbycalculatingthe averagenumberofpatientsprescribedeachdrugfromthecorrespondingfourfinancialyearquarters. AnestimateofthetotalnumberofpeoplereceivinganyARTwasthenobtainedbydividingthetotal numberofpatientsreceivinglamivudineoremtricitabinethroughthes100programbytheproportion oftreatedpatientsinahodreceivingthesamearvdrugs.asasensitivityanalysis,werepeatedthis calculationforothercommonlymutuallyexclusivedrugs,including:1efavirenzandnevirapine;2 Kaletra(lopinavirandritonavirandritonavir;and3stavudineandzidovudinecontainingARVs.Inthis report,wehaveonlyincludedresultsforthelamivudineandemtricitabinemodel. ImportantNote:Priorto2009,theHSDReportprovidedprescribedpatientnumbersbyeach antiretroviralagent.howeverafternotingsomeinconsistencieswiththeirmethodology,theyhave sinceceasedprovidingthesenumbers.foryears2009y2010,insteadwe(thekirbyinstituteevaluated patientnumbersbyusingacombinationoftotalpacksdispensedandanaverage packsyperypatient adjustmentratio.thepacksyperypatientadjustmentfigurewascalculatedfrom2008data,wheretotal packsdispensedandpatientnumberswereavailable.however,duetotherelativelyrecent diversificationofpacksizes,newerdosingschedulesandtheintroductionofantiretroviralagentsthat wereabsentin2008,weareuncertainastohowourpacksyperypatientadjustmentratiohaschanged overtime.thereforewehaveoptednottoreport2011datafortable10.weareworkingwiththe producersofthehsdreporttoamendtheseissuesandarecurrentlyrevisitingourmethodologyfor thesefigures.

14 Table(10:(Number(of(people(dispensed(antiretroviral(treatment(through(the(Highly( Specialised(Drugs((s100(program(by(year(and(antiretroviral(agent( Year(of(prescription 1,2( Antiretroviral(agent( 2004( 2005( 2006( 2007( 2008( 2009( 2010( Nucleoside(analogue(reverse(transcriptase(inhibitors Abacavir 1,542 1, Didanosine 1, Emtricitabine Y Lamivudine 3,219 3,641 2, Stavudine Zalcitabine Zidovudine Lamivudine&Zidovudine 1,989 1,959 1,525 1, Abacavir&Lamivudine Y 212 1,592 2,310 2,608 2,681 2,593 Abacavir,Lamivudine& Zidovudine Tenofovir 2,273 3,076 2,504 1,619 1,381 1,232 1,334 Tenofovir&Emtricitabine Y Y 1,671 3,116 4,131 5,369 4,262 NonSnucleoside(analogue(reverse(transcriptase(inhibitors( Delavirdine Efavirenz 1,656 1,896 2,208 2,413 2,704 2,971 2,079 Nevirapine 2,412 2,697 2,387 2,436 2,629 2,701 2,655 Protease(inhibitors( Amprenavir Atazanavir 590 1,207 1,746 2,034 2,229 2,582 2,603 Darunavir Y Y Y Fosamprenavir Indinavir Lopinavir&ritonavir 1,580 1,543 1,543 1,689 1,737 1,536 1,495 Nelfinavir Ritonavir 879 1,330 1,845 2,071 2,393 3,015 3,217 Saquinavir Tipranavir Y Y Y Fusion(inhibitors( Enfuvirtide Integrase(inhibitor( Raltegravir Y Y Y Y ,090 Combination(Class( Agents( Tenofovir,Emtricitabine &Efavirenz Y Y Y Y Y Y 1,548 Total(patients 3 ( 7,598( 8,453( 9,463( 9,933( 10,596( 11,120( 11,523( Total(cost 4 (($ 000s( 85,293( 98,485( 110,512( 118,847( 135,532( 155,556( 182,888( 1.Thenumberofpeopledispensedeachantiretroviraldrugduringacalendaryearwasestimatedbycalculatingtheaverageofthetotal numberofpeopledispensedeachdrugduringthecorrespondingfinancialyearquarters.numberofpersonyearsforjulyydecember2009 onwardsestimatedfromthehsdprogrampublichospitaldispensednationalpacknumberreportbecauseofchangestos100datacollection methodology. 2Dashes(Yindicatethatdatawerenotavailable.PersonyearsofEtravirineomittedbecauseofinsufficientdata. 3.Totalpatientscalculatedas(Lamivudine+Combivir(Lamivudine&Zidovudine+Trizivir(Abacavir,Lamivudine&Zidovudine+Kivexa (Abacavir&Lamivudine+Emtricitabine+Truvada(Tenofovir&Emtricitabine/theproportionofpatientsintheAustralianHIVObservational Databasereceivinganyofthepreviouslymentioneddrugsineachyear+theestimatednumberofpatientsdispensedwithcombinationclass agents. 4.PublicHospitalExpenditure. Source:(Highly(Specialised(Drugs((S100(Program AHODHIVObservationalDatabaseAnnualReport

15 AHODHIVObservationalDatabaseAnnualReport Australian(HIV(Observational(Database(contributors Asterisks(indicate(steering(committee(members(in(2012. ( New(South(Wales:DEllis,GeneralMedicalPractice,CoffsHarbour;MBloch,TFranic*,SAgrawal,L McCann,TVincent,HoldsworthHouseMedicalPractice,Darlinghurst;DAllen,JLLittle,HoldenStreet Clinic,Gosford;DSmith,CGray,LismoreSexualHealth&AIDSServices,Lismore;DBaker*,RVale,East SydneyDoctors,SurryHills;DJTempleton*,CCO Connor,CDijanosic,RPASexualHealthClinic, Camperdown;EJackson,KMcCallum,BlueMountainsSexualHealthandHIVClinic,Katoomba;M Grotowski,STaylor,TamworthSexualHealthService,Tamworth;DCooper,ACarr,FLee,KHesse,K Sinn,RNorris,StVincent shospital,darlinghurst;rfinlayson,iprone,apatel,taylorsquareprivate Clinic,Darlinghurst;RVarma,JShakeshaft,NepeanSexualHealthandHIVClinic,Penrith;KBrown,C McGrath,VMcGrath,SHalligan,IllawarraSexualHealthService,Warrawong;LWray,PRead,HLu, SydneySexualHealthCentre,Sydney;DCouldwell,ParramattaSexualHealthClinic;DSmith,VFurner, AlbionStreetCentre;Clinic16 RoyalNorthShoreHospital,SFernando;DubboSexualHealthCentre, Dubbo;HoldsworthHouseMedicalPractice,ByronBay,JChuah*;JWatson*,NationalAssociationof PeoplelivingwithHIV/AIDS;CLawrence*,NationalAboriginalCommunityControlledHealth Organisation;BMulhall*,DepartmentofPublicHealthandCommunityMedicine,UniversityofSydney; MLaw*,KPetoumenos*,SWright*,HMcManus*,CBendall*,MBoyd*,TheKirbyInstitute,University ofnsw. ( Northern(Territory:AKulatunga,NRyder,PKnibbs,CommunicableDiseaseCentre,RoyalDarwin Hospital,Darwin. ( Queensland:DRussell,SDowning,CairnsSexualHealthService,Cairns;DSowden,JBroom,KTaing,C Johnston,KMcGill,Clinic87,SunshineCoastYWideBayHealthServiceDistrict,Nambour;DOrth,D Youds,GladstoneRoadMedicalCentre,HighgateHill;MKelly,AGibson,HMagon,BrisbaneSexual HealthandHIVService,Brisbane. South(Australia:WDonohue,O BrienStreetGeneralPractice,Adelaide. ( Victoria:RMoore,SEdwards,RLiddle,PLocke,NorthsideClinic,NorthFitzroy;NJRoth*,JNicolson*,H Lau,PrahranMarketClinic,SouthYarra;TRead,JSilvers*,WZeng,MelbourneSexualHealthCentre, Melbourne;JHoy*,KWatson*,MBryant,SPrice,TheAlfredHospital,Melbourne;IWoolley,MGiles,T Korman,JWilliams,MonashMedicalCentre,Clayton. ( WesternAustralia:DNolan,JSkett,JRobinson,DepartmentofClinicalImmunology,RoyalPerth Hospital,Perth. CoDereviewers: AHODreviewers:DSowden,DJTempleton,JHoy,LWray,KMorwood,TRead,NRoth,IWoolley,M Kelly,JBroom. TAHODreviewers:PCKLi,MPLee,SVanar,SFaridah,AKamarulzaman,JYChoi,BVannary,RDitangco, KTsukada,SPujari,AMakane,OTNg,AJSasisopin. Independentreviewers:MBoyd.

16 Acknowledgments TheAustralianHIVObservationalDatabaseisfundedaspartoftheAsiaPacificHIVObservational Database,aprogramofTheFoundationforAIDSResearch,amfAR,andissupportedinpartbyagrant fromtheu.s.nationalinstitutesofhealth snationalinstituteofallergyandinfectiousdiseases(niaid (GrantNo.U01YAI069907andbyunconditionalgrantsfromMerckSharp&Dohme;Gilead;BristolY MyersSquibb;BoehringerIngelheim;Roche;Pfizer;GlaxoSmithKline;JanssenYCilag.Theviews expressedinthispublicationdonotnecessarilyrepresentthepositionoftheaustraliangovernment. TheKirbyInstituteisaffiliatedwiththeFacultyofMedicine,UniversityofNewSouthWales. Suggested(citation:( TheKirbyInstitute.AustralianHIVObservationalDatabaseAnnualReport.TheKirbyInstitute,The UniversityofNewSouthWales,SydneyNSW.Volume12,Number1:August2012. All(data(in(this(report(are(provisional(and(subject(to(future(revision TheAustralianHIVObservationalDatabasereportisproducedbyTheKirbyInstituteonanannualbasis. Subscriptionisfree,andcanbeobtainedbywritingorcallingTheKirbyInstitute: TheAustralianHIVObservationalDatabasereportisproducedbyTheKirbyInstituteonan annualbasis.subscriptionisfree,andcanbeobtainedbywritingorcallingthekirbyinstitute: TheAustralianHIVObservationalDatabase TheKirbyInstitute CFIBuilding,CornerWest&BoundaryStreets DarlinghurstNSW2010. Tel: Fax: Reportalsoavailableat: ISSN1443Y3907 AHODHIVObservationalDatabaseAnnualReport