Survival analysis of acquired immune deficiency syndrome patients with and without hepatitis C virus infection at a reference center for sexually transmitted diseases/acquired immune deficiency syndrome in São Paulo, Brazil

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

Original

article

Survival

analysis

of

acquired

immune

deficiency

syndrome

patients

with

and

without

hepatitis

C

virus

infection

at

a

reference

center

for

sexually

transmitted

diseases/acquired

immune

deficiency

syndrome

in

São

Paulo,

Brazil

夽

Wong

Kuen

Alencar

_,

_Paulo

_Schiavom

_Duarte

_,

_Eliseu

_Alves

_Waldman

a_{CentrodeReferênciaeTreinamentoDST/AIDS-SP,SãoPaulo,SP,Brazil}

b_{SetordeMedicinaNucleardoInstitutodoCâncerdoEstadodeSãoPaulo(ICESP),SãoPaulo,SP,Brazil}

c_{DepartamentodeEpidemiologiadaFaculdadedeSaúdePúblicadaUniversidadedeSãoPaulo,SP,Brazil}

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Articlehistory:

Received21May2013 Accepted30June2013

Availableonline8November2013

Keywords: HIV Acquiredimmunodeficiency syndrome Hepatitisviruses Survivalanalysis

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Introduction:Survivalofpatientswithacquiredimmunedeficiencysyndromehasimproved

withcombinationantiretroviraltherapy;mortalityduetoliverdiseases,however,hasalso increasedinthesepatients.

Objectives:Toestimatetheaccumulatedprobabilityofsurvivalinhumanimmunodeficiency

virus–hepatitisCviruscoinfectedandnon-coinfectedpatientsandtoinvestigatefactors relatedtoacquiredimmunedeficiencysyndromepatients’survival.

Methods:Non-concurrentcohortstudyusingdatafromsurveillanceinformationsystems

ofacquiredimmunedeficiencysyndromepatientsover13yearsofage.HepatitisCandB, humanimmunodeficiencyvirusexposurecategory,CD4+Tcellcount,agegroup,schooling, race,sex,andfouracquiredimmunedeficiencysyndromediagnosisperiodswerestudied. Kaplan–MeiersurvivalanalysisandCoxmodelwithestimatesofthehazardratioand95% confidenceintervalwereused.

Results:Ofthetotal 2864individualsincluded,withmedianagewas35years,219died

(7.5%),and358(12.5%)werehumanimmunodeficiencyvirus–hepatitisCviruscoinfected. Theaccumulatedprobabilityofsurvivalinhumanimmunodeficiencyvirus–hepatitisCvirus coinfectedpatients,afteracquiredimmunedeficiencysyndromediagnosis,at120months, was0%,38.9%, 83.8%in1986–1993,1994–1996,1997–2002,respectively,and92.8% at96 monthsin2003–2010;survivalinnon-coinfectedpatientsat120monthswas80%,90.2%, 94%in1986–1993,1994–1996,1997–2002,respectively,and94.1%at96monthsin2003–2010. Inthemultivariatemodelthefollowingvariableswerepredictiveofdeath:hepatitisCvirus coinfection(hazardratio=2.7;confidenceinterval2.0–3.6); HepatitisBviruscoinfection (hazardratio=2.4;confidenceinterval1.7–3.6);being≥50yearsold(hazardratio=2.3; confi-denceinterval1.3–3.8);having8–11yearsofschooling(hazardratio=1.6;confidenceinterval

夽_{StudyperformedatFaculdadedeSaúdePública,UniversidadedeSãoPaulo.}

∗ _{Correspondingauthorat:RuaSantaCruz,81,VilaMariana,SãoPaulo,SP,04121-000,Brazil.}

E-mailaddress:[email protected](W.K.Alencar).

1413-8670/$–seefrontmatter©2013 ElsevierEditoraLtda.Allrightsreserved.

1.1–2.3),having4–7yearsofschooling(hazardratio=1.9;confidenceinterval1.3–2.8)and havingupto3yearsofschooling(hazardratio=3.3;confidenceinterval2.0–5.5).

Conclusions:Amongpatientsdiagnosedafter1996,therewasasignificantincreaseinthe

cumulativeprobabilityofsurvivalinhumanimmunodeficiencyvirus–hepatitisCvirus coin-fectedindividuals;amongthosediagnosedwithacquiredimmunedeficiency syndrome from2003to2010, thisprobabilitywassimilarbetweencoinfectedandnon-coinfected patients.

©2013 ElsevierEditoraLtda.Allrightsreserved.

Introduction

TheUnitedNations Program on humanimmunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) statesthat“globally, 34.0million (31.4million–35.9 million) peoplewerelivingwithHIVattheendof2011”,or0.8%of adultsaged15–49years.1_{Survivalofpatientslivingwiththe}

AIDShas increasedinthehighly activeantiretroviral ther-apy(HAART)era,currentlycalledcombinationantiretroviral therapy(cART).2

In Brazil, the median survival time estimated was 5.1 monthsbetween1982and19893_{andincreasedto58months}

in1996;4_{inthesouthandsoutheastregionsofBrazil,59.4%of}

AIDSpatientssurvived108monthsin1998–1999,5_andinSão

Paulo,theaccumulatedprobabilityofsurvivalwas72%at108 monthsin1997–2003.6

AlthoughcARThasbroughtlongersurvivaltoHIV-infected patients,themorbidityandmortalityduetoviralhepatitis, especiallytypeC,hasalsoincreased.7,8 _{Itisestimatedthat}

aboutone-thirdofHIV-infectedindividualsintheworldhave hepatitisCvirus(HCV)coinfection.9_{Infact,decompensated}

liver disease due to HCV has increased as cause of death inpatientswith HIV–HCVcoinfection,7 _{and the prevalence}

ofcirrhosis10_{andofdeathsduetohepatocellularcarcinoma}

havealsobeenincreasinginHIV-infectedpatients.10

Theobjective of the present study wasto estimate the cumulative probability of survival after AIDS diagnosis in HIV–HCV-coinfectedandnon-coinfectedpatientsandto per-formexploratoryanalysistoinvestigatefactorsrelatedtoAIDS patients’survival.

Methods

Thisis alongitudinal observationalstudy, based on medi-calrecords,ofanon-concurrentcohort,ofpatientsreceiving careinapublicreferralcenterforthetreatmentofsexually transmitteddiseasesandAIDSinSãoPaulocity,Brazil(CRT DST/AIDS-SP,CRT).Thisclinichasalsobecomeareferral cen-terforhepatitistreatmentsince2004,anditisalsothehead officeoftheSãoPauloStateProgramforSexuallyTransmitted DiseasesandAIDS.

TheMetropolitanRegionofSão Paulocity had,in2010, a population of 19.667.558 inhabitants according to local census,11_{and74,308AIDScasesnotifiedfrom1980to2009.}12

ThesampleincludedinthisstudycomprisesallAIDScasesin individualsaged13yearsorolderbeingfollowedinourreferral center,andwithcompletemedicalrecords.

Patientswere excludedfromthepresent studyifhe/she hadadiagnosisofAIDSrelatedcomplex(syndromeincluding fatigueandswollenlymphnodes)orifthedeathcertificate statedAIDSasthecauseofdeathwithoutalaboratoryexam to confirmHIV infection.These caseswere more common before1996,especiallybefore1987(HIVviruseswere identi-fiedin1983and 1986).13–15 _{Pregnancy wasalsoacriteriaof}

exclusioninthisstudy.

Forthepurposeofinclusioninthisstudy,HCVinfection wasdefinedbyserologicaltests(ELISAorEIA,inany genera-tion)andthequalitativeorquantitativedetectionofHCVRNA, bythetimeofAIDSdiagnosisorinthenearestdate(uptotwo yearsbeforeorafter).

Thesourcesofdatainthisstudywerethenational notifica-tiondatabasesforAIDScases(SINANWindowsupto2006and SINANNetfrom 2007on),the CRT-Epidemiological Surveil-lanceSystem,andtheCRT-LaboratorySystem.Afourthsource wastheSãoPauloStatesurveillancesystem,calledBIP-AIDS (integratingSIM, SistemadeInformac¸ãosobreMortalidade, civilnotaryofficesandSEADEFoundation,Fundac¸ãoSistema EstadualdeAnálisedeDados).Whensomeinformationwas not available in these electronic systems, it was searched directlyfrommedicalrecords.

A special spreadsheet was created for data collection includingthefollowingindependentvariables:AIDS diagno-sisperiods(1986–1993,1994–1996,1997–2002and2003–2010), patient’sage,gender,ethnicity/race,yearsofschooling,CD4+ TcellcountatAIDSdiagnosis,HCVinfectionandhepatitisB surfaceantigen(HBsAg)inaperiodnexttoAIDSdiagnosis(up totwoyearsbeforeorafter).Theelapsedtimefromdiagnosis untildeath,inmonths,wastakenasthedependentvariable. ThesourceofexposuretoHIVwasregisteredinthree cat-egories:from heterosexualrelationship,menwhohavesex withmen(MSM),andbytheuseofintravenousdrugs(IDU). Transmission by blood transfusions, accidents and others wereexcludedfromthesurvivalanalysis.Wheninformation was initiallyregistered as“unknown”, the originalmedical recordintheclinicwassearchedmanuallyforcompletion.

Thefinaldateforsurvivalcalculationwasestablishedas April30,2011.Losstofollowupanddeathbyother-than-AIDS orunknowncauseswerecensored(incompletefollowup).

Statisticalanalysis

Initially, a descriptive analysis was performed, presenting absolute and relative frequencies, comparing patients infected and uninfected with HCV, observing distributions andcharacteristicsofusersinrelationtothestudyvariables

19475 AIDS Registered in the national databases

Lack of lab results in database

Information of AIDS only in the death certificate ARC syndrome in death certificate

Without follow - up data

Followed - up elsewhere or institutionalized Inconclusive serology

Data collection period finished

Assessed for eligibility 1163 5904 400 4739 Excluded ₁₁₇₁ 136 537 5425 2561 2864 2506 HCV– HCV+ 358 AIDS patients included in the study

• died in first year after AIDS diagnosis • Only HIV -positive (not fulfilling criteria for AIDS) • Problems with medical records

Fig.1–Flowchartofpatientinclusioninthestudy(period: July1986–April2010).

ofinterest.Chi-squaretestwasusedtocompareinfectedand uninfectedcasesbyHCV.

Kaplan–Meieranalysisofsurvivalwasperformed,witha cumulative probability of survival with AIDS estimated in months,accordingtoeachvariableofinterestandperiodof diagnosis of AIDS. Statistical significance was assessed by thelog ranktest.ACox regressionorproportional hazards modelwas chosentocalculaterisk orhazard ratio (HR)in survivalanalysis,withaconfidenceinterval(CI)of95%,and the variable “period ofdiagnosis” was used as a stratum. Univariate analysis was followed by multivariate analysis. Associationswereconsideredstatisticallysignificantwitha significancelevel ofless than5%.Microsoft Excel2003and STATA software, version 10.0,were usedfor the statistical analysis.

Thestudyprotocolwasdesignedinaccordancewiththe NationalHealthCommitteeguidelines,andwasapprovedby CRT’sandFaculdadedeSaúdePública–SãoPauloUniversity’s EthicsCommitteeswiththe protocolnumber CRT002/2010 andFSP-USP44/2010.

Results

FromJuly1986toApril2010,atotalof19,475AIDScaseswere registeredinthemajornationaldatabases(SINANWindows and Net).However,14,050neededto beexcludedfrom the studyforthereasonsshowninFig.1anddescribedindetail below.Theremaining5425AIDScaseswerethereforeassessed foreligibility:2561werefurtherexcludedbecausetheydiedin firstyearoffollow-upafterAIDSdiagnosis,becausetheydid notfulfillthecriteriaforAIDScharacterization,orbecauseof problemswiththemedicalrecords(suchasthelackofan iden-tifyingnumber).Anotherreasonforexclusionwasthelackof aHCVRNAtestforhepatitisCconfirmation (hepatitiswas registeredascirrhosis).Therefore,thisstudyisbasedon2864 casesofAIDSpatients,amongwhom358werecoinfectedwith HCV.

Thereasonsforexclusionswere:lackoflaboratoryexams inthedatabase;medicalrecordsbringinginformationofAIDS

2003 - 2010

1997 - 2002

1994 - 1996

1986 - 1993

Time from AIDS diagnosis (months)

Log rank = 71,3 p < 0,001 1,00 0,75 0,50 0,25 0,00 0 50 100 150 200 250 Sur viv al

Fig.2–SurvivalanalysisofAIDSpatientsaccordingtothe periodofAIDSdiagnosis.

onlyinthedeathcertificate,or,otherwise,allegedARC symp-tomsinthedeathcertificate,withoutclinicalorlabexams; casesnotregisteredintheCRTEpidemiologicalsurveillance system database, which contains follow-up data; patients beingfollowed-upinotherinstitutions,admittedinhospitals, orsubjectsofclinicalresearchprotocols;inconclusive sero-logyandfinally,patientswereexcludedwhentheperiodfor datacollectionwasfinished.

Table1summarizesthepatients’demographicand clini-calcharacteristicsamongthe2864AIDScases,infectedornot withHCV.

In our study, 76.3% ofthe patients were men,70.8% of whiterace,69.2%aged30–49yearswithamedianageof35 years(minimum13andmaximum79),58.2%with4–11years ofschooling,54.1%wereMSM,93.7%hadCD4+Tcellcount <350cell/mm3_{,12.5%wereHIV–HCVcoinfected,7.5%had}

Hep-atitis B,and44.2% ofpatients were AIDSdiagnosed inthe 1997–2002period.

Regarding schoolingyears,42%ofcoinfected individuals had 4–7 years of schooling while 40.1% of non-coinfected patientshad12schoolyearsormore.TheIDUHIVexposure categorywasidentifiedin45.1%amongcoinfectedsubjects while 58.6% of non-coinfected was MSM. Hepatitis B was morecommoninnon-coinfectedHIV–HCV(8.1%versus3.6%;

p=0.003).

Amongthe 2864AIDSpatients, 219(7.6%)died between 1986and2010.

Fig. 2 shows the Kaplan–Meier survival curves of the patients according to the AIDS diagnosis period. A higher rate ofsurvival was seen inthe post-cART: 1997–2002 and 2003–2010AIDSdiagnosisperiod(logrank=71.3;p<0.001).

Fig. 3 shows the survival analysisof monoinfected and HIV–HCV coinfected AIDSpatients according toAIDS diag-nosisperiod.Theaccumulatedprobabilityofsurvivalamong coinfectedpatientsat120monthsafterAIDSdiagnosiswas 0%forthosediagnosedintheperiodbetween1986and1993, 38.9%in1994–1996and83.8%inthe1997–2002period. Sur-vivalinnon-coinfectedpatientsat120monthswas80%,90.2%, 94%in1986–1993,1994–1996,1997–2002,respectively.Finally, inthe2003–2010AIDSdiagnosisperiod,becauseofashorter observationtime, thesurvivalamongcoinfected was92.8% andamongnon-coinfectedwas94.1%at96months.

Table1–CharacteristicsofpatientsaccordingtoHCVinfection(CRT-DST/AIDS-SP,1986–2010).

Patients’characteristics Cohort pa

AIDS (n=2.506) AIDS/HCV (n=358) Total (n=2.864) n % n % n % Sex Female 594 23.7 84 23.5 678 23.7 0.920 Male 1.912 76.3 274 76.5 2.186 76.3 Raceb White 1.764 70.8 253 70.9 2.017 70.8 0.983 Non-white 727 29.2 104 29.1 831 29.2 Agerangec Upto29yearsold 604 24.0 82 22.9 686 24.0 0.732 30–49yearsold 1.729 69.0 254 70.9 1.983 69.2 50yearsorolder 173 6.9 22 6.1 195 6.8 Agec Median 35 35 35

Inter- quartilerange(25%–75%) 30–41 30–41 30–41

Minimum 13 20 13 Maximum 79 76 79 Education(years)c,d Upto3 95 3.9 36 10.1 131 4.7 <0.001 4–7 490 20.0 150 42.0 640 22.8 8–11 881 36.0 112 31.4 993 35.4 12ormore 983 40.1 59 16.5 1.042 37.1

HIVexposurecategoryc,e,f

Heterosexual 924 37.5 112 31.7 1.036 36.8 <0.001 MSM 1.443 58.6 82 23.2 1.525 54.1 IDU 96 3.9 159 45.1 255 9.1 CD4+Tcellcountc,g <350cell/mm3 _{2.218 93.8 295 93.1 2.513 93.7 0.598} ≥350cell/mm3 _{146 6.2 22 6.9 168 6.3} HepatitisB(HBsAg)c No 2.303 91.9 345 96.4 2.648 92.5 0.003 Yes 203 8.1 13 3.6 216 7.5

PeriodofAIDSdiagnosis

2003–2010 1.090 43.5 71 19.8 1.161 40.5 <0.001

1997–2002 1.047 41.7 218 60.9 1.265 44.2

1994–1996 302 12.1 61 17.1 363 12.7

1986–1993 67 2.7 8 2.2 75 2.6

MSM,menwhohavesexwithmen;IDU,injectingdrugusers;HBsAg,surfaceantigenofhepatitisB.

a _{Concerningthecomparisonofthegroups(Pearson).}

b _{Dataignored=16.}

c _{ThediagnosisofAIDS.}

d _{Dataignored=58.}

e _{Dataignored=46.}

f _{2Caseswereexcludedtransfusion.}

g _{Dataignored=183.}

ResultsofCoxunivariateanalysisarepresentedinTable2. HCVcoinfectionwasapredictorofdeath(HR=2.9,CI2.1–3.8). Otherpredictorsofdeathwere:HepatitisBvirus(HBV) coinfec-tion(HR=2.1,CI1.4–3.0),havinguptothreeyearsofschooling (HR=4.0,CI2.4–6.6),havingfourtosevenyearsofschooling (HR=2.4,CI1.6–3.5),having8–11yearsofschooling(HR=1.7,CI 1.1–2.4),IDUexposurecategory(HR=1.8,CI1.3–2.7),andbeing 50yearsorolder(HR=2.0,CI1.2–3.4).

ThefinalmultivariateCoxregressionmodelispresentedin

Table3.Thepredictivevariablesofdeath,adjustedforother variables, were: HCV coinfection (HR=2.7, CI 2.0–3.6), HBV coinfection(HR=2.4,CI1.7–3.6),having8–11yearsofschooling (HR=1.6,CI1.1–2.3),havingfourtosevenyearsofschooling (HR=1.9, CI 1.3–2.8), havingup to threeyears of schooling (HR=3.3,CI2.0–5.5),andbeing50yearsorolder(HR=2.3,CI 1.3–3.8).

Table2–UnivariateCoxmodelanalysisofpredictivevariablesofdeath,CRTDST/AIDS-SP,1986–2010.

Patient’scharacteristics AIDSn=2864 Deathn=219 HR 95%CI p-Value

Sex Male 2.186 176 1 – – Female 678 43 0.8 0.6–1.1 0.149 Agea Upto29yearsold 686 49 1 – – 30–49yearsold 1.983 147 1.1 0.8–1.6 0.480

50yearsoldorolder 195 23 2.0 1.2–3.4 0.005

Skincolorb

White 2.017 163 1 – –

Non-white 831 56 0.8 0.6–1.1 0.285

HIVexposurecategorya,c,d

Heterosexual 1.036 81 1 – – MSM 1.525 94 0.8 0.6–1.0 0.083 IDU 255 42 1.8 1.3–2.7 0.001 Schooling(years)a,e 12ormore 1.042 43 1 – – 8–11 993 74 1.7 1.1–2.4 0.009 4–7 640 75 2.4 1.6–3.5 <0.001 Upto3 131 25 4.0 2.4–6.6 <0.001 TCD4+a,f_cellcount ≥350cell/mm3 _{168 12 1 – –} <350cell/mm3 _{2.513 196 0.7 0.4–1.3 0.308} HepatitisB(HBsAg)b No 2.648 185 1 – – Yes 216 34 2.1 1.4–3.0 <0.001 HepatitisCb No 2.506 154 1 – – Yes 358 65 2.9 2.1–3.8 <0.001

MSM,menwhohavesexwithmen;IDU,injectingdrugusers;HBsAg,hepatitisBsurfaceantigen;HR,hazardratio;CI,confidenceinterval.

a _{InthediagnosisofAIDS.}

b _{Unknowndata=16.}

c _{Unknowndata=46.}

d_{2caseswereexcludedduetobloodtransfusion.}

e _{Unknowndata=58.}

f _{Unknowndata=183.}

Discussion

Concurrentinfectionbytwoormoreagentsismoreharmful tohumanhealth.16

HIV–HCVcoinfectionwasindependentlyassociatedwith increasedriskofdeathinthisstudy.Branchetal.havefound 50%increasedmortalityamongcoinfectedpatientscompared with non-coinfected.17 Although some other studies have not observed the same association,18 _{recent studies have}

consistently shown the burdenof deathamongcoinfected individuals.19–21

Asalreadyseeninotherstudies,4_{thetimeofAIDS}

diagno-siswassignificantlyassociatedwithsurvivalinourstudy.This isprobablyduetocART,whichhaschangedthenatural his-toryofandclinicalevolutionofHIVinfectionandisavailable free-of-chargeforBrazilianpatients,distributedbythepublic healthsystemsince1996.22

Thesurvival curves in our study were significantly dif-ferent between HCV–HIV coinfected and non-coinfected patients,aresultsimilartothatofBonacinietal.23_However,

this difference was notsignificant for the periods ofAIDS diagnosisbetween2003and2010.Thisresultcanbeexplained by the immunosuppression controlin patients undergoing cART24_{andbytheinclusion,in2002,ofpegylatedinterferon}

fortreatinghepatitisCinBrazil.25

InourstudyCD4+Tcellcountwasnotassociatedwith sur-vival.Petersetal.havefoundthathepatitisCviruscoinfection doesnotinfluenceCD4+TcellcountrecoveryinHIV-1infected patients with maximum virologic suppression.26

Neverthe-less, byimproving immune function, cART can slower the clinicalevolutionofHCVinfection27_{andreducesignificantly}

therateofdeathsrelatedtohepatitisCliverdisease.28 Theuseofillicitinjecteddrugsisknowntobeariskfactor forHCVinfection.Inourstudy,drugusewasnot indepen-dentlyassociatedwithdeath,butthisassociationwasfound byotherauthors.29

The prevalence of HCV infection has been estimated to have reached10 million injected drug users worldwide, whereas1.2millionwouldhavebeeninfectedbyHBV.30_The

importanceofthisliesonthefactthatcARTislessbeneficial inpatientswithcoinfection,andadherencetotherapy,which

1,00 0,75 0,50 0,25 Log rank = 1,95 p = 0,163 Log rank = 19,8 p < 0,001 Log rank = 39,8 p < 0,001 Log rank = 0,75 p < 0,383 0,00 1,00 0,75 0,50 0,25 0,00 1,00 0,75 0,50 0,25 0,00 1,00 0,75 0,50 0,25 0,00 0 50 100 150 200 250 0 50 100 150 200 0 20 40 60 80 100 0 50 100 150 200

Time from AIDS diagnosis (months) Time from AIDS diagnosis (months) Time from AIDS diagnosis (months) Time from AIDS diagnosis (months)

Sur viv al Sur viv al Sur viv al Sur viv al AIDS AIDS/HCV AIDS AIDS AIDS/HCV AIDS/HCV AIDS AIDS/HCV

Fig.3–SurvivalanalysisofAIDSpatientsaccordingtotheperiodofAIDSdiagnosis((A)1986–1993,(B)1994–1996,(C) 1997–2002,(D)2003–2010)andthepresenceofhepatitisCviruscoinfection.

Table3–MultivariateCoxmodelanalysisofpredictors

ofdeath,CRTDST/AIDS-SP,1986–2010.

Patient’scharacteristics n=2.864 p-value

HR 95%CI Agea Upto29yearsold 1 – – 30–49yearsold 1.2 0.9–1.7 0.258 50yearsorolder 2.3 1.3–3.8 0.002 Schooling(years)a,b 12yearsormore 1 – – 8–11 1.6 1.1–2.3 0.017 4–7 1.9 1.3–2.8 0.001 Upto3 3.3 2.0–5.5 <0.001 HepatitisB(HBsAg)a No 1 – – Yes 2.4 1.7–3.6 <0.001 HepatitisCa No 1 – – Yes 2.7 2.0–3.6 <0.001

HR,hazardratio;CI,confidenceinterval;HBsAg,hepatitisBsurface

antigen.

a _{InthediagnosisofAIDS.}

b _{Unknowndata=58.}

isalreadyaprobleminHIV–HCVcoinfectedpatients,6_canbe

evenloweramongdrugusers.31,32_{Ameta-analysispublished}

this year hasshown that treatmentofaddiction resultsin higherhepatitistreatmentcompletionincludingantivirals.33

Another coinfection significantly associated with increased risk of death in our study was HBV–HIV coin-fection, as already reported by other authors.34 _HIV–HBV

coinfectedindividuals haveacceleratedhepaticfibrosis and reduced rates ofspontaneousresolution ofacuteinfection onset.35_{ButtheinfluenceofHBVinfectioninthecourseof}

AIDSisnotknown,andserologicaltestingand vaccination arerecommendedtoHIVinfectedindividuals.

Theassociationofincreasedsurvivalandhigher school-ingcameasnosurpriseinthisstudy,asithadbeenalready shownbyothers,36_{aswellastheassociationwithadvanced}

age,4,37,38_{afindingwhichcanberelatedtobiologicalfactors,}

socialstigma,quantityandqualityofsocialrelationships.39,40

Wedidnotfindsignificantassociationofsurvivalandgender andraceinourstudy,butliteratureresultsarenot consen-sualregardingthisissue,41–43_{andpossiblyitcanberelatedto}

socialfactorssuchasaccesstocare44,45_{andadherencerelated}

togender.42,43

TheexclusionofdeadpatientswhodidnothaveHCVRNA resultsinthe medicalrecord andthe exclusionofpatients with late AIDS diagnosis (i.e. patients who died within 12

monthsfromdiagnosis)mayhaveresultedinoverestimation ofsurvivalratesandarelimitationsofthisstudy.

Conclusions

Amongpatientsdiagnosedafter1996,therewasasignificant increaseinthecumulativeprobabilityofsurvivalinHIV–HCV coinfectedpatientscomparedtopreviousyears,andamong those receiving AIDS diagnosis inthe period from 2003 to 2010,thisprobabilitywassimilarbetweencoinfectedand non-coinfectedpatients,reflectingapossibleimpactofeffective treatmentofhepatitisCandcARTonsurvival.

Theresultsofourstudyareimportantandrelevantforthe clinicalmanagementandclinicalpoliciesdesignedforpeople livingwithHIV.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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