Original article

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Original article

Predictors of advanced disease and late presentation in new HIV diagnoses reported to the surveillance system in Spain

Jesús Oliva

^a^,^b^,∗

, Mercedes Díez

^a^,^b

, Silvia Galindo

^a

, Carlos Cevallos

^c

, Ana Izquierdo

^d

, Javier Cereijo

^e

, Arantxa Arrillaga

^f

, Antonio Nicolau

^g

, Ana Fernández

^h

, Mara Álvarez

ⁱ

, Jesús Castilla

^j,b

, Eva Martínez

^k

, Irene López

^l

, Nuria Vivés

^m^,^b

aPlanNacionalsobreelSida/CentroNacionaldeEpidemiología,UnidaddeEpidemiologíadelVIH/SIDAyConductasdeRiesgo,CentroNacionaldeEpidemiología,InstitutodeSalud CarlosIII,Madrid,Spain

bCIBERdeEpidemiologíaySaludPública(CIBERESP),Spain

cServiciodeEpidemiología,SubdireccióndePromocióndelaSaludyPrevención,ConsejeríadeSanidad,ComunidaddeMadrid,Spain

dServiciodeEpidemiologíayPrevención,DirecciónGeneraldeSaludPública,ServicioCanariodelaSalud,Sta.CruzdeTenerife,Spain

eServizodeControldeEnfermidadesTransmisibles,DirecciónXeraldeInnovacióneXestióndaSaúdePública,XuntadeGalicia,Spain

fPlandePrevenciónyControldelSidadelPaísVasco,SanSebastián,Spain

gServiciodeEpidemiología,DirecciónGeneraldeSaludPública,ConsejeríadeSaludyConsumodelGobiernoBalear,PalmadeMallorca,Spain

hServiciodeVigilanciayAlertasEpidemiológicas,DirecciónGeneralSaludPúblicayParticipación,ConsejeríadeSaludyServiciosSanitariosdelPrincipadodeAsturias,Oviedo,Spain

iSubdireccióndeEpidemiología,ServicioExtreme˜nodeSalud,JuntadeExtremadura,Mérida,Spain

jInstitutodeSaludPúblicadeNavarra,Pamplona,Spain

kServiciodeEpidemiologíayPrevenciónSanitaria,ConsejeríadeSaluddelGobiernodeLaRioja,Logro˜no,Spain

lServiciodeEpidemiología,ConsejeríadeSanidadyConsumodelaCiudadAutónomadeCeuta,Spain

mCentred’EstudisEpidemiològicssobrelesInfeccionsdeTransmissióSexualiSidadeCatalunya(CEEISCAT),InstitutCatalàd’Oncologia(ICO),DireccióGeneraldeSalutPública, GeneralitatdeCatalunya,Badalona,Spain

a r t i c l e i n f o

Articlehistory:

Received30April2013 Accepted27June2013

Availableonline21December2013

Keywords:

HIV

Advanceddisease Latepresentation Spain

Surveillance

a b s t r a c t

Objective: Topresentsurveillancedataonadvanceddisease(AD)andlatepresentation(LP)ofHIVin Spainandtheirdeterminants.

Methods: WeincludedallnewHIVdiagnosesnotiﬁedbytheautonomousregionsthatconsistently reportedsuchcasesthroughouttheperiod2007–2011.Coveragewas54%ofthetotalSpanishpopulation.

Datasourcesconsistedofclinicians,laboratoriesandmedicalrecords.ADwasdefinedasthepresenceof aCD4cellcount<200cells/␮LinthefirsttestafterHIVdiagnosis,whileLPwasdefinedasthepresence ofaCD4cellcount<350cells/␮LafterHIVdiagnosis.Oddsratiosandtheir95%confidenceintervals(OR, 95%CI)wereusedasthemeasureofassociation.LogisticregressionswerefittoidentifypredictorsofAD andLP.

Results:Atotalof13,021newHIVdiagnoseswereincluded.Amongthese,dataontheoutcomevariable wereavailablein87.7%.ThemedianCD4countatpresentationwas363(interquartilerange,161–565).

Overall,3356(29.4%)patientsmetthedeﬁnitionofADand5494(48.1%)wereclassiﬁedasLP.BothADand LPincreasedwithageandwereassociatedwithmalesexandinfectionthroughdruguseorheterosexual contact.AllimmigrantsexceptwesternEuropeansweremorepronetoADandLP.Multivariatemodels disaggregatedbysexshowedthattheeffectofageandregionoforiginwasweakerinwomenthanin men.

Conclusions: DespiteuniversalhealthcarecoverageinSpain,men,immigrantsandpeopleinfected throughdruguseorheterosexualcontactseemtobeexperiencingdifﬁcultiesingainingtimelyaccessto HIVcare.

Determinantesdeenfermedadavanzadaypresentacióntardíaenlosnuevos diagnósticosdeVIHnotiﬁcadosalsistemadevigilanciaepidemiológica enEspa ˜na

Palabrasclave:

VIH

Enfermedadavanzada Presentacióntardía Espa ˜na

Vigilanciaepidemiológica

re s u m e n

Objetivo:Sepresentanlosdatosdevigilanciasobreenfermedadavanzadaypresentacióntardíadelos nuevosdiagnósticosdeVIHenEspa ˜na,ysusdeterminantes.

Métodos:SeincluyerontodoslosnuevosdiagnósticosdeVIHde2007–2011enelámbitodelascomu- nidadesautónomasquenotificarondeformaconstantedurantetodoelperiodo(54%delapoblación espa ñola).Lafuentedeinformaciónfueronclínicosylaboratorios.Sedefiniócomoenfermedadavanzada unrecuento<200linfocitosCD4/␮lenlaprimeradeterminacióntraseldiagnóstico,ycomopresentación tardía<350linfocitosCD4/␮l.Seusaronlaoddsratioysuintervalodeconfianzadel95%comomedida

∗ Correspondingauthor.

E-mailaddress:[email protected](J.Oliva).

http://dx.doi.org/10.1016/j.gaceta.2013.06.009

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deasociación.Paraelanálisismultivariadodelosfactoresasociadosaenfermedadavanzadaypre- sentacióntardíaseajustóunmodeloderegresiónlogística.

Resultados: Seincluyeron13.021nuevosdiagnósticos,deloscualesel87,7%teníainformacióndelava- riabledeestudio.LamedianadeCD4fuede363(rangointercuartílico:161–565).Duranteelperiodo,3.356 pacientes(29,4%)cumplíanladeﬁnicióndeenfermedadavanzaday5.494(48.1%)seclasiﬁcaroncomo presentacióntardía.Tantolaenfermedadavanzadacomolapresentacióntardíaaumentabanconlaedad, seasociabanalsexomasculinoyalatransmisiónatravésdelusodedrogasinyectadasoheterosexual.

Serinmigrantedecualquierorigen,exceptodeEuropaOccidental,seasociabaaenfermedadavanzaday presentacióntardía.Desagregandoporsexo,elefectodelaedadydelaregióndeorigenfuemásdébilen lasmujeresqueenloshombres.

Conclusión: ApesardelacoberturauniversalenEspa ˜na,loshombres,losinmigrantes,losusuariosde drogasinyectadasylaspersonasinfectadasporrelacionesheterosexualesparecentenermásdiﬁcultad paraaccederalseguimientoclínico.

Introduction

EarlyHIVdiagnosisandtreatmentareessentialinthecontrolof theHIVepidemicworldwide.HIV-infectedpatientspresentinglate inthecourseoftheirinfectionhavehigherratesofmorbidityand mortalityandrequiremorehealthcareresourcesthanthosepre- sentingearlier.^1,2Furthermore,HIVdiagnosismotivatesinfected peopletoadoptmeasurestoreducetheriskofinfectingothers, andtreatmentwithhighlyactiveantiretroviraltherapy(HAART) hasbeenshowntogreatlyreduceHIVtransmission.^3–5

Differentcriteriahavebeenusedintheliteraturetodefinediag- nosticdelayand latepresentationamongHIV-infectedpatients, which generally include the level of CD4 cells and the presence/absence of AIDS-defining diseases.⁶ Recently, European groupshaveproposedthat“latepresentation”bedefinedasthe presence of an AIDS condition or CD4cell count <350cells/␮L atpresentationfor care,leaving theterm“advanceddisease”to describethepresenceofeitheranAIDSconditionoraCD4cellcount

<200cells/␮Latpresentation.^7,8

Latepresentationremainsamajorchallengeforthecontrolof HIVinEurope,andreducingthetimebetweeninfectionandentryto careisapriorityfortheregion.^9–11MeasuringCD4cellsatpresen- tationforcareisroutinepracticeinmostcountries–inparticular intheWesternpartoftheregion.But,in2011,only56%ofnew HIVdiagnosesreportedtotheEuropeanCentreforDiseaseControl (ECDC)fromtheEUcountrieshadCD4data.¹²

In Spain,epidemiological surveillanceonnew HIVdiagnosis isperformedthroughtheSistemadeInformaciónsobre Nuevos DiagnósticosdeVIH(SINIVIHinitsSpanishacronym)whichcol- lectsepidemiologicalandclinicaldataonpeoplenewlydiagnosed withHIV.Thissystem,expectedtobeimplementedcountrywide inthenearfuture, currentlyincludesdatafrom17outof 19of Spain’sautonomousregions(AR).CD4cellcountatpresentationis collected,andthecompletionofthevariableisgood.

PreviouslypublishedSINIVIHdatashowedthatalmost40%of newHIVdiagnosesduringtheperiod2003–2007had<200CD4, andthatthissituationwasmorelikelytooccurinmen,peopleover 30years,intravenousdrugusers(IDU)andheterosexuals;factors associatedwithhaving<200CD4werethesameinSpaniardsand migrants,buttheassociationwasstrongerinthelattergroup.¹³

Theobjectivesofthispaperaretopresentdataontheimmuno- logicalsituationofthenewHIVdiagnosesreportedtotheSINIVIH inthe period2007–2011,and todeterminewhetherpredictors forhaving<200CD4atentrytocarearedifferentfrompredictors ofhaving<350CD4.

Methods

AllpeoplenewlydiagnosedwithHIV–accordingtotheEuro- peancasedeﬁnition¹⁴–andreportedduringtheperiod2007–2011

totheSINIVIHintheARofAsturias,BalearicIslands,CanaryIslands, Catalonia, Ceuta, Extremadura, Galicia,Madrid,Navarre, Basque CountryandLaRioja,wereincludedinthestudy.Theseregions comprise54%ofthetotalSpanishpopulationandwereselectedfor theanalysisbecausetheyreportedtotheSINIVIHduringthewhole studyperiod.

Information was collected, using the standard surveillance forms,onthefollowingvariables:dateofHIVdiagnosis,dateof notiﬁcation,age,gender,reportingautonomousregion,transmissionmode,ﬁrstCD4cellcountperformedafterHIVdiagnosisand countryorsubcontinentoforigin.Datasourcesweretheattending cliniciansandthelaboratories,andinformationwascompletedby reviewingclinicalrecordswherenecessary.

ThestudywasperformedaccordingtotheSpanishlegislation ondataprotectionwhichdoesnotrequireinformedconsentfor thecollectionofsurveillancedata,asisthecaseinthisstudy(Ley 33/2011,de4deoctubre,GeneraldeSaludPública,artículo41.2).

EliminationofduplicatereportswasmadeineachARbypublic healthstaff,butinter-regionalduplicateswerenoteliminatedsince dataweresentwithoutpersonalidentiﬁerstotheNationalCenter ofEpidemiology,wheretheanalysiswasperformed.

Forthepurposeofthisstudy,“advancedHIVdisease”(AD)was deﬁnedasthepresenceofaCD4countbelow200cells/␮Linthe ﬁrstanalysisperformedafterHIVdiagnosis.“Latepresentation”

(LP)wasdeﬁnedasthepresenceofaCD4countbelow350cells/␮L intheﬁrstanalysisperformedafterHIVdiagnosis.

Datadistributionsbyvariablesrelatedtoperson,placeandtime wereperformed.The ² testwasused toevaluatetheassocia- tionbetweencategoricalvariables.Theoddsratio(OR)andits95%

conﬁdenceinterval(95%CI)wereusedasthemeasureofassociation.ToidentifyvariablesassociatedwithADorLP,multivariable logisticregressionmodelswereﬁtintheoverallpopulationand disaggregatedbysex;forthesemodelsonlycaseswithinforma- tiononCD4wereused.Additionally,inordertoassessthepotential biasintroducedbyexcludingsickerpatientswithoutaCD4count,a sensitivityanalysiswasperformed,assumingthatallpatientswith- outaCD4countwerelatepresenters.Allstatisticalanalyseswere performedusingStataStatisticalSoftware:Release11.1, College Station,TX:StataCorporation(2009).

Results

Atotalof13,021newHIVcaseswerereportedduringthestudy period,ofwhich11,426(87.7%)hadinformationonCD4cellcount atpresentation.Themajority(81%)ofthenewHIVdiagnoseswere male,and83.4%hadbeeninfectedthroughsexualcontact,espe- cially through sex between men; the median age at diagnosis was35years(inter-quartilerange:29–43).Caseswithinformation onCD4countdifferedfromthosewithoutthisinformationwith regardtotransmissionmode,regionoforiginandyearordiagnosis:

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Table1

CharacteristicsofnewHIVdiagnoses.Spain,^a2007–2011.

Characteristics Totalcases

n(%)

CaseswithCD4cellcount n(%)

CaseswithoutCD4cellcount n(%)

Sex

Female 2471(19.0) 2148(18.8) 322(20.2)

Male 10,550(81.0) 9278(81.2) 1273(79.8)

AgeatHIVdiagnosis(years)^b

All 35(29–43) 35(29–43) 34(28–42)

Female 34(28–42) 34(28–42) 34(28–41)

Male 35(29–43) 35(29–43) 34(28–42)

Transmissionmode^c

MSM 6435(49.4) 5846(51.2) 589(36.9)

IDU 981(7.5) 837(7.3) 145(9.1)

Hetero 4423(34.0) 4021(35.2) 401(25.1)

Other 61(0.5) 49(0.4) 12(0.8)

Unknown/NA 1121(8.6) 673(5.9) 448(28.1)

Regionoforigin^c

Spain 7862(60.4) 6943(60.8) 920(57.7)

WesternEurope 586(4.5) 509(4.5) 77(4.8)

EasternEurope 380(2.9) 311(2.7) 69(4.3)

LatinAmerica 2811(21.6) 2501(21.9) 309(19.4)

Sub-SaharanAfrica 1120(8.6) 936(8.2) 184(11.5)

NorthAfrica 137(1.1) 118(1.0) 19(1.2)

Other/NA 125(1.0) 108(0.9) 17(1.1)

Yearofdiagnosis^c

2007 2513(19.3) 2204(19.3) 309(19.4)

2008 2847(21.9) 2553(22.3) 294(18.4)

2009 2625(20.2) 2347(20.5) 278(17.4)

2010 2746(21.1) 2341(20.5) 405(25.4)

2011 2290(17.6) 1981(17.3) 309(19.4)

Total 13,021(100) 11,426(100) 1595(100)

HIV:humanimmunodeﬁciencyvirus;MSM:menwhohavesexwithmen;IDU:injectingdruguse;hetero:heterosexualcontact;NA:notavailable.

aAsturias,BalearicIslands,CanaryIslands,Catalonia,Ceuta,Extremadura,Galicia,LaRioja,Madrid,Navarre,andBasqueCountry.

b Median(interquartilerange).

c p-Value<0.05.DifferencesbetweencaseswithandwithoutCD4cellcount.

Sub-Saharanmigrantsandinjectingdrugusers(IDU)wereover- representedamongpeoplelackingthisinformation;furthermore, theproportionofcaseswithunknowninformationontransmission modewashigheramongthosewithoutdataonCD4count(Table1).

Median CD4 at presentation was 363 (inter-quartile range:

161–565).Overall,3356(29.4%)patientsmetthedeﬁnitionofAD.

TheproportionofpatientswithADwashigherinwomen,increased withage,andwashighestamongcaseswhosetransmissionmode wasIDUorheterosexual ascompared withmenwhohave sex withmen(MSM).Byregionoforigin,ADprevalencewasgenerally greaterinmigrantsthaninSpaniards(Table2).Inthemultivariate analysisoftheglobaldatatheprobabilityofhavingADwashigher inmen(OR:1.3;95%CI:1.1–1.5),intheagegroups30–39years (OR:1.7;95%CI:1.5–1.9),40–49years(OR:2.8;95%CI:2.5–3.2) and≥50years(OR:4.4;95%CI:3.8–5.1),ascomparedtotheage group20–29years;inpeopleoriginatingfromEastEurope(OR:

1.7;95%CI:1.3–2.1),LatinAmerica(OR:1.4;95%CI:1.3–1.6),Sub- SaharanAfrica(OR:1.4;95%CI:1.2–1.7),andNorthAfrica(OR:1.6;

95%CI:1.1–2.4);andamongIDU(OR:2.0;95%CI:1.7–2.4)andthose infectedbyheterosexualcontact(OR:2.4;95%CI:2.1–2.7)(Table3).

Atotalof5494(48.1%)subjectspresentedlate.Thegroupsmost affectedbyLP were thesameas those affectedby ADand the associationswereinthesamedirection;neverthelessinthemulti- variateanalysistherewereslightdifferencesinthestrengthofthe associations(Tables2and3).

Whendisaggregatingbysex,themultivariateanalysesshowdif- ferenteffectofageandregionoforigininmenthaninwomen.In men,ADandLPclearlyincreaseforcasesolderthan29whileamong womentheeffectisweakerandtheincreaseintheagegroup30–

39isontheedgeofstatisticalsigniﬁcance.Theeffectofregionof originisalsoweakerinwomenthaninmen(Tables4and5).

When the sensitivity analysis assuming that cases without informationonCD4werelatepresenterswasperformedfactors associatedwithADandLPdidnotchange.

Discussion

ThisstudypresentssurveillancedataonCD4countatpresen- tationforcareinnewHIVdiagnosesinasettingcovering54%of thetotalSpanishpopulation.Theresultsshowthatsubjectswho hadinformationonCD4cellcountaredifferentfromthosewhodid not,thatalmosthalfofnewHIVdiagnosespresentedlatetomed- icalcareand30%hadAD,andthatpredictorsofLPandADarethe same.

SurveillancedataonCD4countatentryintocarearescarcein theEU.¹²Inthisstudyinformationwasavailableinalmost90%of registries;however,theresultsshowthatthelackofinformationis notrandomlydistributed,suggestingthattraditionallydisadvan- tagedsubjects,suchasIDUandmigrants,mighthaveproblemsin accessingcareafterbeingdiagnosed,eveniftheyareentitledto freeheathcare,asisthecaseinSpain.

The prevalence of AD and LP is similar to that found in France or theUK, and higher than theﬁgures reported in The NetherlandsortheCzechRepublic.¹²OutsidetheEU,studiescar- riedout–usingthesamedeﬁnition–intheUnitedStatesandHong KongreportagreaterproportionofAD.^15,16

InSpain,HIVtestingispartofroutineprenatalcare,andthis probablyexplains,atleasttosomeextent,whywomenareless likelytopresentlate.Thefactthat(asshowninthemultivariate analysesdisaggregatedbysex)theeffectofageandregionofori- ginonADandLPareweakerinwomenthaninmenalsosupport thisexplanation.Thishasalsobeenobservedinotherdeveloped

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Table2

AdvancedHIVdiseaseandlatepresentationinnewHIVdiagnoses.Spain,^a2007–2011.

Characteristics NumberofcaseswithCD4cellcount n(%completenessineachcategory)

AdvancedHIVdisease (<200cell/␮L)

Latepresentation (<350cell/␮L)

n (%) n (%)

Sex

Female 2148(86.9) 727 (33.8) 1131 (52.6)

Male 9278(87.9) 2629 (28.4) 4363 (47.0)

Age(years)

0–19 206(85.1) 22 (10.7) 47 (22.8)

20–29 3040(87.1) 532 (17.5) 1132 (37.2)

30–39 4197(87.5) 1130 (26.9) 1912 (45.6)

40–49 2604(88.2) 982 (37.7) 1479 (56.8)

≥50 1379(89.7) 690 (50.0) 924 (67.0)

Transmissionmode

MSM 5846(90.8) 1193 (20.4) 2285 (39.1)

IDU 837(85.3) 285 (34.5) 445 (53.2)

Hetero 4021(90.9) 1587 (39.5) 2365 (58.8)

Other 49(80.3) 16 (32.7) 20 (40.8)

Unknown/NA 673(60.0) 275 (40.8) 379 (56.3)

Regionoforigin

Spain 6943(88.3) 1916 (27.6) 3121 (44.9)

WesternEurope 509(86.9) 138 (27.1) 232 (45.6)

EasternEurope 311(81.8) 108 (34.7) 154 (49.5)

LatinAmerica 2501(89.0) 736 (29.4) 1278 (51.1)

Sub-SaharanAfrica 936(83.6) 369 (39.4) 581 (62.1)

NorthAfrica 118(86.1) 49 (41.5) 68 (57.6)

Other/NA 108(86.4) 40 (37.0) 60 (55.6)

Yearofdiagnosis

2007 2204(87.7) 688 (31.2) 1110 (50.4)

2008 2553(89.7) 753 (29.5) 1235 (48.4)

2009 2347(89.4) 723 (30.8) 1187 (50.6)

2010 2341(85.3) 641 (27.4) 1063 (45.4)

2011 1981(86.5) 551 (27.8) 899 (45.4)

Total 11,426(87.8) 3356 (29.4) 5494 (48.1)

HIV:Humanimmunodeﬁciencyvirus;MSM:menwhohavesexwithmen;IDU:injectingdruguse;hetero:heterosexualcontact;NA:notavailable.

countrieswhereantenatalHIVscreeningistherule.¹⁷Datafrom theUnitedKingdomshowthatmedianCD4atHIVdiagnosisissig- niﬁcantlyhigherinpregnantwomenthaninwomendiagnosedin otherunitsandinheterosexualmen.¹⁸

TheassociationofADwithageis alreadyknown.13,15,16,19–25

AgeisalsoassociatedwithLP.Themostwidelyacceptedexplana- tionisthatriskperceptionandfrequencyoftestingdecreasewith increasingage.^20,25Anotherpossibleexplanationrelatestothenat- uralhistoryofthedisease,whichclinicallyandimmunologically evolvesmorerapidlyinolderpatients.²⁵

Incomparison withothertransmissionmodes,MSMarethe least likely topresent late, while peopleinfected through het- erosexualcontactaremorelikely,ﬁndingsalsocommontoother countries.16,21,23,24Theseresultsprobablyreﬂectriskperceptions onthepartofbothpatientsandproviders,andpointtotheneed toscaleupHIVtestingamongheterosexuals,inparticularamong men.

Spainexperienced overlapping epidemics of HIV and heroin injectionfromthe1980stothemid-1990s.²⁶Thehighlikelihood ofAD/LPinIDUissurprising,sinceriskperceptioninthisgroupis veryhighandHIVtestingisroutinelyofferedtopatientsindrug treatmentcenters,prisonsandatallcontactswiththehealthcare system.Apossibleexplanationcouldbethatratherthanbeingthe consequenceoflatediagnosisthisfindingistheresultofworse linkagetocareamongIDUduetobarriersinaccessingcarespecific tothisgroup.Thefactthatinourdata,theproportionofIDUwitha CD4countperformedwithinthefirst3monthsafterHIVdiagnosis islowerthanforothertransmissionmodes(60%vs.77%,p<0.05) supportsthisexplanation.

Previouslypublishedstudies,bothinSpainandabroad,iden- tify beinga migrant asa risk factor for late HIV diagnosisand presentationforcare.13,19,27,28Worriesaboutdiscrimination,lan- guagebarriers,theperceptionofHIVasadeadlydisease,andlack ofconfidenceabouttheconfidentialityofresultshavebeennoted asbarriersforHIVtestingamongmigrants,^29,30andmigrants,in particularillegalmigrants,haverestrictedaccesstocareinmost countries.³¹SomeofthesefactorsmightbeoperatinginSpain,even thoughallmigrantsareentitledtoHIVcareonthesamebasisas Spaniards.Ontheotherhand,immigrationisaveryrecentphe- nomenoninSpainanditispossiblethat,tosomeextent,figuresfor ADandLPinimmigrantsreflectfactorsoperatingintheircountryof originratherthaninSpain.Unfortunately,dateofentryintoSpain isnotyetcollectedintheSINIVIH;thusthishypothesiscannotbe exploredfurther.

Thisstudyhassomelimitations.Theresultscannotbeextrap- olatedtothewholecountrybecausedataarenot countrywide.

Nevertheless,studycoverageishigh,under-reportingisestimated tobemoderate,andparticipatingARdonotdifferfromtherestin termsoffactorsinfluencingAD/LP,sinceHIVcareisprovidedfree ofcharge,inthecontextofauniversalhealthcaresystem,inthe wholecountry.Furthermore,duetothelackofinformationonthe concomitantdiagnosisofAIDSandHIV,itcouldbearguedthatour dataunderestimateADandLP,sincesomeauthorsincludepres- enceofAIDSasanadditionaldefiningcriteriaforthetwoevents.⁷ Whileitistruethatthisinformationisnotcurrentlyavailablein allparticipatingAR,somedocollectit;analysisofavailabledata showthatifthiscriterionwereincludedinthedefinitionofADand LP,theproportionofADinourdatawouldincreasefrom29.4%to

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Table3

FactorsassociatedwithadvanceddiseaseandlatepresentationinnewlydiagnosedHIVinfections.Spain,^a2007–2011.N=11,426.

Characteristics AdvancedHIVdisease(<200cell/␮L)^b Latepresentation(<350cell/␮L)^b

AdjustedOR 95%CI AdjustedOR 95%CI

Sex

Female 1 1

Male 1.3 (1.1–1.5) 1.4 (1.2–1.5)

Age(years)

0–19 0.4 (0.3–0.7) 0.5 (0.3–0.7)

20–29 1 1

30–39 1.7 (1.5–1.9) 1.4 (1.2–1.5)

40–49 2.8 (2.5–3.2) 2.2 (2.0–2.5)

≥50 4.4 (3.8–5.1) 3.3 (2.9–3.8)

Transmissionmode

MSM 1 1

IDU 2.0 (1.7–2.4) 1.9 (1.6–2.2)

Hetero 2.4 (2.1–2.7) 2.1 (1.9–2.4)

Unknown/NA 2.3 (1.9–2.8) 1.8 (1.5–2.1)

Regionoforigin

Spain 1 1

WesternEurope 1.1 (0.9–1.3) 1.1 (0.9–1.3)

EasternEurope 1.7 (1.3–2.1) 1.3 (1.1–1.7)

LatinAmerica 1.4 (1.3–1.6) 1.6 (1.5–1.8)

Sub-SaharanAfrica 1.4 (1.2–1.7) 1.7 (1.5–2.0)

NorthAfrica 1.6 (1.1–2.4) 1.5 (1.0–2.1)

Yearofdiagnosis

2011 1 (0.9–1.2) 1 (1.0–1.3)

2007 1.1 (0.8–1.1) 1.1 (0.9–1.2)

2008 1.0 (0.9–1.2) 1.0 (1.0–1.3)

2009 1.1 (0.8–1.1) 1.2 (0.8–1.1)

2010 0.9 0.9

VIH:Humanimmunodeﬁciencyvirus;OR:oddsratio;CI:conﬁdenceinterval;MSM:menwhohavesexwithmen;IDU:injectingdruguse;hetero:heterosexualcontact;

NA:notavailable.

b Multivariablelogisticregression,ORand95%CIsadjustedforalllistedvariablesandreportingAutonomousRegion.

Table4

FactorsassociatedwithadvanceddiseaseandlatepresentationinnewlydiagnosedHIVinfectionsinmen.Spain,^a2007–2011.N=9278.

Age(years)

0–19 0.5 (0.3–1.0) 0.6 (0.4–0.9)

20–29 1 1

30–39 1.9 (1.6–2.2) 1.4 (1.3–1.6)

40–49 3.1 (2.7–3.6) 2.2 (2.0–2.5)

≥50 5.3 (4.5–6.3) 3.7 (3.2–4.4)

Transmissionmode

Hetero 1 1

IDU 0.9 (0.7–1.1) 0.9 (0.8–1.1)

MSM 0.4 (0.3–0.5) 0.5 (0.4–0.6)

Unknown/NA 1.0 (0.8–1.2) 0.8 (0.7–1.0)

Regionoforigin

Spain 1 1

WesternEurope 1.1 (0.9–1.3) 1.1 (0.9–1.3)

EasternEurope 1.7 (1.2–2.3) 1.3 (1.0–1.8)

LatinAmerica 1.5 (1.3–1.7) 1.6 (1.5–1.8)

NorthAfrica 1.6 (1.1–2.5) 1.3 (0.8–2.0)

Yearofdiagnosis

2011 1 (1.0–1.3) 1 (1.0–1.3)

2007 1.1 (0.9–1.2) 1.2 (0.9–1.2)

2008 1.0 (1.0–1.3) 1.1 (1.1–1.4)

2009 1.1 (0.8–1.1) 1.3 (0.9–1.2)

2010 1.0 1.0

VIH:Humanimmunodeﬁciencyvirus;OR:oddsratio;CI:conﬁdenceinterval;MSM:menwhohavesexwithmen;IDU:injectingdruguse;hetero:heterosexualcontact;

NA:notavailable.

b Multivariablelogisticregression,ORand95%CIsadjustedforalllistedvariablesandreportingAutonomousRegion.

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Table5

FactorsassociatedwithadvanceddiseaseandlatepresentationinnewlydiagnosedHIVinfectionsinwomen.Spain,^a2007–2011.N=2148.

Age(years)

0–19 0.4 (0.2–0.8) 0.3 (0.1–0.5)

20–29 1 1

30–39 1.2 (1.0–1.6) 1.2 (1.0–1.5)

40–49 2.0 (1.6–2.7) 1.9 (1.5–2.5)

≥50 2.2 (1.6–3.0) 2.0 (1.5–2.8)

Transmissionmode

Hetero 1 1

IDU 0.8 (0.5–1.1) 0.8 (0.6–1.1)

Unknown/NA 1.3 (0.8–2.1) 1.2 (0.8–1.9)

Regionoforigin

Spain 1 1

WesternEurope 1.2 (0.7–2.3) 1.3 (0.7–2.4)

EasternEurope 1.5 (0.9–2.3) 1.3 (0.9–2.0)

LatinAmerica 1.3 (1.1–1.7) 1.5 (1.2–1.9)

NorthAfrica 1.6 (0.7–3.5) 2.0 (0.9–4.4)

Yearofdiagnosis

2011 1 (0.6–1.1) 1 (0.7–1.2)

2007 0.8 (0.6–1.0) 0.9 (0.6–1.1)

2008 0.8 (0.6–1.1) 0.8 (0.6–1.1)

2009 0.8 (0.5–1.0) 0.8 (0.5–1.0)

2010 0.7 0.7

VIH:Humanimmunodeﬁciencyvirus;OR:oddsratio;CI:conﬁdenceinterval;IDU:injectingdruguse;hetero:heterosexualcontact;NA:notavailable.

bMultivariablelogisticregression,ORand95%CIsadjustedforalllistedvariablesandreportingAutonomousRegion.

32.7%,andtheproportionofLPfrom48.1%to50.0%.Ontheother hand,sincetheSINIVIHhasbeenimplementedonlyrecentlyin someoftheparticipatingAR,itispossiblethatsomecasesreported asnewHIVdiagnosesinthestudyperiodwereactuallypreviously diagnosedpatientsfalselyclassiﬁedasnewduetothelackofan establishedHIVcaseregistry;ifthiswerethecase,bothADand LPmaybeoverestimatedinthisstudy.Finally,duplicateswithin eachautonomousregionhavebeeneliminatedbutthisisnotthe casewiththosewithinautonomousregions.Wethinkthatbetween 5–10%ofregistriescouldbeduplicated,inwhichcasetheincidence ofnewHIVdiagnoseswouldbeoverestimated;however,itisnot clearhowthiswouldaffectlatepresentationandfactorsassociated withit.Neverthelessweexpecttobeabletoeliminateduplicates withinautonomousregionsinthenearfuture.

Insummary,thisstudyshowsthatoneoutoftwonewHIVdiag- nosesinSpainpresentslateforcare,andthatsomesub-populations aremorevulnerablethanotherstothisproblem.Recently,guide- lines for scaling-up HIV testing have been published by some EuropeancountriesandtheECDC.³²InSpain,aworkinggroupaim- ingtoaccomplishasimilartask,includingappropriatelinkageto HIVcare,hasbeenappointed.Hopefully,implementationofguide- linesinthenearfuturewillhelptodecreaselateaccesstoHIV diagnosisandcare.Finally,enhancedsurveillance,coupledwith implementationof SINIVIHinthewholecountry,isessentialto monitorguidelinesimplementationandprovidebetterinforma- tiononLPanditsdeterminantsatbothnationalandinternational levels.

Editorinchargeofthearticle PereGodoy,M.D.

Authorshipcontributions

Thenumberofauthorsisjustiﬁedbytheexistenceofaperson responsibleforthenewHIVdiagnosessystemineachautonomous

Whatisknownonthistopic?

Advanceddiseaseandlatepresentationremainsamajor challengeforthecontrolofHIV.Reducingtimebetweeninfec- tionandentrytocareisapriority.InSpain,epidemiological surveillanceonnewHIVdiagnosisisperformedthroughthe Sistemade Informaciónsobre NuevosDiagnósticos deVIH which collectsepidemiological and clinical data onpeople newlydiagnosed.

Whatdoesthisstudyaddtotheliterature?

InSpain,dataonCD4countatentryintocarewereavailable inalmost90%ofnewHIVdiagnosesnotiﬁedtothesurveillance systemintheperiod2007–2011.Somesociallydisadvantaged groups,suchasIDUandmigrants,weremorelikelytohave missing data on CD4 count, suggesting that they might haveproblemsinaccessingcareafterbeingdiagnosed.Inthe studyoneoutoftwonewHIVdiagnosesinSpainpresentedlate forcare.Malepatients,migrantsandpeopleinfectedthrough heterosexualcontactorsharingofinjectionequipmentwere morelikelytopresentlateforcare.

region.All authorsparticipated in data collectionand aggrega- tionandqualitycontrolofthedatabasesintheircorresponding autonomousregionsandalsoperformedin-depthreviewsofall thedraftsofthemanuscript.J.Olivaperformeddataaggregation, quality control, planning and analysis of the overall database, preparedthetables,wrotethefirstdraftofthemanuscriptand participatedinsuccessivedraftsuptothefinalversion.M.Diez conceivedthestudyandparticipatedinalldraftsuptothefinal version.S. Galindocontributedtodatamanagement andanaly- sisoftheoveralldatabaseandperformedin-depthrevisionsofall thedraftsofthemanuscript.C.Cevallos,A.Izquierdo,J.Cereijo,

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A. Arrillaga, A. Nicolau, A. Fernández, M. Álvarez, J. Castilla, E. Martínez, I. López and N. Vives carried out data collection and aggregation and quality control in the databases of their autonomousregionsandperformedin-depthrevisionsofallthe draftsofthemanuscript.Allauthorshavereviewedandapproved theﬁnalmanuscript.

Funding None.

Conﬂictsofinterest None.

Acknowledgments

The authors wish to thank all the health professionals that reportedcasesandcontributedinonewayoranothertoimproving thequalityofthedata.TheauthorsalsothankKathyFitchforher reviewoftheEnglishtranslation.

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