w w w . e l s e v ie r . c o m / l o c a t e / b j i d
The
Brazilian
Journal
of
INFECTIOUS
DISEASES
Original
article
Prevalence
and
characteristics
of
HIV/HBV
and
HIV/HCV
coinfections
in
Tuscany
Monia
Puglia
a,
Cristina
Stasi
a,b,∗,
Monica
Da
Frè
a,
Fabio
Voller
aaRegionalHealthAgencyofTuscany,Florence,Italy
bUniversityofFlorence,DepartmentofExperimentalandClinicalMedicine,Florence,Italy
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t
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f
o
Articlehistory: Received22July2015 Accepted17November2015 Availableonline31December2015
Keywords: HIV HBV HCV Coinfections
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Introduction:Worldwideabout30%ofHIV-infectedpatientsarecoinfectedwithHCVorHBV. TheHIV/HCVcoinfectionismorecommoninindividualswhohaveahistoryofdrug addic-tion.TheaimsofthisstudyweretoassesstheHCVandHBVprevalenceinHIV-infected patientsandanalyzetheircharacteristics.
Methods:We considered the new HIV diagnoses notified by the regional surveillance systemofTuscanyfrom2009to2013.Descriptiveanalyseswereconductedonthe socio-demographiccharacteristics,routesoftransmission,andreasontoperformthetest.In coinfectedpatientsweassessedtheriskforbeinglatepresenter(LP)ortheriskofhaving AIDS.
Results:In5yearsofsurveillancea totalof1354newHIVdiagnoseswerenotified:1188 (87.7%)wereHIValone,106(7.8%)HIV/HCV,56(4.1%)HIV/HBV,and4(0.33%)HIV/HCV/HBV. Themainriskfactorwasinjectiondrugusein52.8%ofHCV/HIVcases,whileinHIV/HBV patientsthemainriskfactorwassexualexposure.HIV/HBVcoinfectedpatientsshowed worseclinicalandimmunologicalfeaturesthanHIVandHIV/HCVpatients:78.6%hadCD4 countlessthan350mm−3(vs.54.6%and62.1%,respectively)and39.4%hadAIDS(vs20.7% and7.6%).TheriskforbeingLPtriplesforHIV/HBV(OR2.98;95%IC:1.56–5.70)thanpatients withHIValone.
Conclusions:WehaveobservedlessadvanceddiseaseinHIVandHCV-HIVpatients com-paredwithHBV–HIVcoinfectedpatients.Moreover,ourresultsshowahigherprevalenceof HIV/HCVamongdrugaddictsandintheage-group35–59,correspondingtothosebornin yearsconsideredmostatriskforaddiction.Thisstudyalsoconfirmsthefindingofaless advancedHIVdiseaseinHIV/HCVcoinfectedpatients.
©2016ElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
TheAcquiredImmuneDeficiencySyndrome(AIDS),reported forthe first time inliterature in1981, representsthe final
∗ Correspondingauthor.
E-mailaddress:cristina.stasi@gmail.com(C.Stasi).
clinical stageofinfectionbythe humanimmunodeficiency virus(HIV).1
The advent of Highly Active Anti-Retroviral Therapy (HAART)haschangedthenaturalhistoryandepidemiologyof HIVinfection.Inparticular,themortalityratehasdecreased
http://dx.doi.org/10.1016/j.bjid.2015.11.007
1413-8670/©2016ElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/
asaconsequenceofthereductioninthenumberofpeople whodeveloptheconditionofAIDS.In2012,peoplelivingwith HIVinfection orAIDSwere35 millionworldwide,whilethe newdiagnoseswereabout2.3million,withadecreaseof33% comparedto2001,whennewinfectionswereapproximately 3.4million.2
Sub-SaharanAfricaisthemostaffectedregion.Recently,1 millionnewdiagnoseswerereported.SouthandSouth-East Asia reported270thousand newdiagnoses.InEurope,HIV infection remainsaproblemofmajorpublic health impor-tance. Italy, in 2012, reported 3853 new diagnoses of HIV infectionand715casesofAIDS,amountingtoanincidence rateof6.5and1.7casesper100,000inhabitants,respectively. Theserates,althoughlowerthantheEuropeanaverage,are higherthantheaverageofotherEuropeanUnionand Euro-peanEconomicArea(EU/EEA)countries.3
Worldwide,about1milliondeathsperyearareattributed tohepatitisBorCviralinfections(HBVorHCV).This repre-sents2.7%ofallcausemortality.Themostcommoncauses includehepatocellularcarcinoma.Moreover,57%ofcasesof livercirrhosisand78%oflivercancerarecausedbyHBVand HCV.4HBV,HCV,andHIVsharethesametransmissionroutes. Ithasbeenestimatedthatworldwideabout30%ofpeoplewith HIVarecoinfectedwithHCVorHBV.5Usually,theHIV/HCV co-infectionismorecommoninindividualswhohaveahistory ofdrugaddiction.6 Severalstudies havealsodemonstrated thatsuchcoinfectionspresentamajorriskforliverfibrosis progressionandsubsequentevolutiontocirrhosis.7
Basedonthesepremises,theobjectivesofthisstudywere toevaluatetheprevalenceofHIV/HCVandHIV/HBV coinfec-tionsinTuscanyandtoanalyzetheircharacteristics.
Methods
InItaly,AIDSwasdeclaredanationallynotifiableinfectious diseasebyMinisterialDecreeNo.288ofNovember28,1986and wassubsequentlysubjectedtospecialnotificationbyfillingin aspecialform.In2008,newdiagnosesofHIVinfectionswere alsosubjectedtomandatorynotification.
InTuscany,themanagementoftheHIVregional surveil-lance system hasbeen improvedsince 2009and requiring notificationofnewHIVdiagnoses.
Inthisstudy,weconsideredthecasesofnewHIVdiagnoses notifiedinTuscanyfrom2009to2013totheRegional Surveil-lance System. This dataset contained information about patientgender,age, nationality,modeoftransmission, rea-sonforbeingtested,CD4lymphocytescount,HIVviralload, andAIDSdiagnosis.Weanalyzedtheprevalenceof coinfec-tion with HBV (based on the presence of antigen surface – HBsAg), HCV (based on the presence of anti-HCV anti-body,which identifiespeople whohavebeen infectedwith thevirus),orboth.Weconsideredthefollowingclinicaland immunologicalconditions:(1)latepresentation(LP):persons presentingforcarewithaCD4countbelow350cells/Lorwith anAIDS-definingevent(suchasbacterialinfections, candidia-sis,cryptococcosis,cytomegalovirusretinitis,Kaposisarcoma, lymphoma),irrespective ofCD4cell count;(2) presentation withadvancedHIVdisease(AHD):personspresentingforcare withaCD4countbelow200cells/LorwithanAIDS-defining
event,regardlessoftheCD4cellcount8;and(3)AIDS condi-tion,definedashavingHIVand anopportunisticinfection, regardlessoftheCD4cellcount.
Socio-demographic characteristics, risk factors, reasons for being HIV tested, and the clinical and immunological features of patients were analyzed in the following four groups of patients: HIV monoinfection, HIV/HBV, HIV/HCV, and HIV/HBV/HCV infectedpatients. A chi-squaretest was performedtoanalyzetheassociationbetweeneachvariable andtheconditionofcoinfection.
Multivariate logistic regression analysis was used to exploreifthecoinfectionconditionswereassociatedwithLP, AHDorAIDS,adjustingforgender,age,nationality,andrisk factors.
StatisticalanalyseswereperformedusingSTATA SE12.0 statisticalsoftware.
Results
Infiveyearsofsurveillance(2009–2013),1402newHIV diag-noseswerenotifiedinTuscany,withanincidencerateof7.6 per 100,000residents. InformationonHBV orHCV coinfec-tionwasavailablefor1354(96.6%ofthetotalnumberofthe newHIVdiagnoses)HIVinfectedpatients:1188(87.7%)were monoinfected, 106(7.8%)werecoinfectedwithHIV/HCV, 56 (4.1%)withHIV/HBV,and4(0.3%)withHIV/HCV/HBV.
IntheHIVmonoinfected,HIV/HBV,and HIV/HCVgroups 20.9%,14.3%,and 18.9%werefemale, respectively(Table1). Italiannationalitywassignificantlydifferentinthreegroups of patients: 91.5% ofHIV/HCV patients, 60.7% ofHIV/HBV, and74.8%ofHIVmonoinfection.Most(73.6%)oftheHIV/HCV patientswerediagnosedinthe35–59agegroup(medianage 43),comparedto50.0%ofHIV/HBVpatients(medianage38) and55.6%ofHIVmonoinfectedpatients(medianage39).
AmongHIV/HCVcases52.8%had beeninfectedthrough injection drug use. In HIV/HBV and HIV monoinfected patients,themainriskfactorforviraltransmissionwassexual exposure(Fig.1).
HIV testingwas mainly donedue tosuspicionofa dis-easeorHIV-relatedclinicalsignsofacuteinfection,especially inHIV/HBVpatients(62.5%).Thetestwasperformed sponta-neouslyduetotheperceptionoftheriskofinfectionby14.3% ofHIV/HBV,26.7%ofHIVmonoinfected,and21.7%ofHIV/HCV patients.Moreover,amongHIV/HCVpatients,7.6%and12.3% ofthepatientsperformedthetestinprisonorbecauseitwas offeredbytheServiceforDrugAddiction(Table2).
HIV/HBVpatientspresentedaworseclinicaland immuno-logicalpicturecomparedwithHIVmonoinfectedandHIV/HCV patients.HIVviralloadofHIV/HBVandHIV/HCVcoinfected patientswasnotsignificantlydifferent.InHIV/HBVpatients the proportionsofLP(78.6%)andAHD (64.3%)were higher compared toHIV/HCV (61.3%and 41.5%) and HIV monoin-fected patients (55.2% and 39.6%). AIDS was diagnosed in 39.3%,20.7%, and 7.6%ofHIV/HBV,HIV monoinfected and HIV/HCVpatients,respectively.
Adjustingforgender,age,nationality,andriskfactors,the HIV/HBV patientsshowed ahigherrisk tobeLPcompared to HIV monoinfected patients (OR3.04; 95% CI:1.55–5.95). TheriskofhavingAHDwasalsohigherinHIV/HBVpatients (OR2.84;95%CI:1.57–5.14) comparedtoHIVmonoinfected
Table1–Socio-demographiccharacteristicsofHIV,HIV/HBV,HIV/HCV,HIV/HCV/HBVpatientsnotifiedinTuscany (2009–2013).
Socio-demographiccharacteristics HIV HIV/HBV HIV/HCV HIV/HCV/HBV p-value
n % n % n % n % Gender Male 940 79.1 48 85.7 86 81.1 3 75.0 0.647 Female 248 20.9 8 14.3 20 18.9 1 25.0 Agegroup 0–16 4 0.3 0 – 0 – 0 – 0.050 17–34 427 35.9 21 37.5 20 18.9 1 25.0 35–59 660 55.6 28 50.0 78 73.6 3 75.0 ≥60 97 8.2 7 12.5 8 7.6 0 – Nationality Italian 889 74.8 34 60.7 97 91.5 4 100.0 0.000 Foreign 299 25.2 22 39.3 9 8.5 0 –
Table2–ReasonsforgettinganHIVtestinHIV,HIV/HBV,HIV/HCV,HIV/HCV/HBVadultpatientsnotifiedinTuscany (2009–2013).
ReasonsforgettinganHIVtesta HIV HIV/HBV HIV/HCV
HypothesisofanHIV-relatedpathology 38.2 46.4 31.1
Hypothesisofasexuallytransmitteddisease 9.0 12.5 4.7
Situationofacuteinfection 7.9 3.6 8.5
Totalnumbertestedforacuteinfection/STD/HIVrelateddisease 55.2 62.5 44.3
Spontaneously 26.7 14.3 21.7
Gynecologicalconsultationduringpregnancy 4.1 3.6 2.8
Offeredafterinformativecampaign 1.9 1.8 0.9
OfferedbytheServiceforDrugAddiction 0.9 1.8 12.3
Carriedoutbeforesurgery 1.4 3.6 –
Offeredinprison 0.6 1.8 7.6
Offeredbeforeblood/organ/tissue/spermdonation 1.9 1.8 –
Offeredbyfamilyconsultant/gynecologist(ifnotpregnant) 0.7 – –
Noriskfactor 0.4 – –
Other 6.0 7.1 10.4
a Multipleresponses.
patients. No statistically significant difference was found betweenHIV/HCV andHIVmonoinfectedpatients(Table3). ComparedtoHIVmonoinfectedpatients,HIV/HBVpatients hadahigherriskofAIDS(OR2.44;95%CI:1.35–4.43)while theriskofHIV/HCVpatientsseemedlower(OR0.23;95%CI: 0.10–0.52).
Discussion
Toourknowledge,thisstudyshowsforthefirsttimethatthe clinical andimmunological featuresofHIV/HBVcoinfected
patientsaremoreseverecomparedtothoseco-infectedwith HIV/HCVandHIVmonoinfectedpatientsatthetimeofHIV diagnosis.HIVwasdiagnosedeitherinprisonorbythe Ser-viceforDrugAddictioninalmost20%ofHCV/HIVcoinfected patients, whichmayhavecontributedtothe lessadvanced HIVdiseaseinthispopulation.Infact,druguseisthemain riskfactorfortransmissioninthisgroupofpatients.Moreover, about15–45%positiveforanti-HCVantibodiesspontaneously clearthevirus.
TheHIV/HBVco-infectionwascommoninforeignersand they had both age and risk factors similar to those who
Table3–Multivariatelogisticregressionanalysis.EstimateofrelativeriskforHIV,HIV/HBV,HIV/HCVtobeLP,AHDor AIDS.AdultpatientsnotifiedinTuscany.2009–2013.
Latepresenter AdvancedHIVdisease AIDS
%a OR IC95% % OR IC95% % OR IC95%
HIV 55.2 1.00 – 39.6 1.00 – 20.7 1.00 –
HIV/HBV 78.6 3.04 1.55–5.95 64.3 2.84 1.57–5.14 39.3 2.44 1.35–4.43
HIV/HCV 61.3 1.24 0.75–2.05 41.5 0.81 0.49–1.34 7.6 0.23 0.10–0.52
Oddsratioandconfidenceintervalsat95%adjustedbygender,age,nationality,modeoftransmission. a Thetotalamountofthethreeconditionsisnot100%,becauseeachgroupmaybeinsideothergroups.
100% 80% 60% 40% 20% 0%
HIV HIV/HBV HIV/HCV
Unknown Other Transfusion IDU MSM Heterosexual
Fig.1–HIVtransmissionrouteinHIV,HIV/HBV,HIV/HCV,
HIV/HCV/HBVinfectedadultpatientsnotifiedinTuscany
(2009–2013).
wereHIVmonoinfected.However,thesepatientshadaworse immunologicalpictureatthetimeofHIVdiagnosiscompared toHIV/HCVco-infectedpatients,probablybecausethesexual transmissionwasthemainriskfactorinHIV/HBVcoinfected patients, with subsequent less perception of the infection transmissionrisk,thereforetheyonlyperformedthetestafter experiencingHIV-relatedsymptoms.Moreover,theywereat higherriskofhavingLP,AHD,orAIDScomparedtoHCV coin-fectedpatients.Accordingwiththesefindings,recentstudies pointedoutthatHBVinfectioncomplicatesthemanagement ofHIVinfection.Infact,patientswithchronicHBVatthetime ofHIVdiagnosishadanimpairedCD4recovery,an acceler-atedimmunologicdeterioration,andasignificantlyhigherrisk ofanAIDSordeathevent.9,10 ThisissimilartoHIVinduced impairmentofHBV,whichinturninfluencesnegativelythe courseandprogressionofHIVdisease.
WealsofoundahighprevalenceofHBV–HIVcoinfection inforeigners.In1991,ItalyinitiateduniversalHBV vaccina-tionforallnewbornsand12-year-oldadolescents.Sincethe vaccinationprogramshadadifferentpaceindeveloping coun-tries,thehighprevalenceamongforeignerscouldbedueto non-compliancewithItaly’svaccinationprogram.11
Theintroductionofblood-screeningforHCVintheearly 1990s strongly decreased HCV transmission from blood transfusions. Our data also confirm the results of several studiesthatshowedahighprevalenceofHCVcoinfectionin HIV-infectedintravenousdrugusers.6,12,13Moreover,this co-infection wasmoreprevalent inpatientsaged35–59years, correspondingtothosebornintheyearsatmajorriskfordrug abuse.Babyboomersarepeoplebornduringthepost-World WarII,approximatelybetweentheyearsof1946and1964.HCV infectionandfattyliverdiseasearemorecommonintheBaby Boomersandmayplayamoredominantroleastheyage,14 probablybecauseagingofthebabyboomercohortwillsoon
comprisealargeproportionofpersonswhohaveusedillicit drugsintheirlifetimes.Arecentcross-sectionalstudy con-ductedinBrazilshowedthattheprevalencerateofHIV-HCV coinfectionwas6.9%among848HIV-infectedpatients receiv-ingcareatreferencecentersintheMidwestRegionofBrazil.15 Thisalsoconfirmsthelessadvanceddiseaseinthesepatients, probablyduetoahigherperceivedriskofdisease,whichcould leadthemtotestearlier.Evenafteradjustingforgender,age, nationality,andtransmissionroute,wewereabletoshowthat HIV/HCVhadalowerriskofhavingAIDSdiagnosisatthetime ofdetectionofHIVinfectioncomparedtoHIVmonoinfected patients.
HCV screeninginHIV-infectedpatientsishighly recom-mended inorder to treatHCV infection whenappropriate. Currently, interferon-free treatment regimens are available and they require shorterperiods of treatment (3 months). These regimens are freeof the associatedsubstantial side effects, and preliminary results suggest that these treat-mentsarealsoeffectiveinpatientswithcirrhosis(somefor 6months).16
Inconclusion,ourdatashowthatbothageandrisk fac-torsforHIV/HBVcoinfectedpatientsaresimilartothatofHIV monoinfectedpatients.Moreover,theprevalenceofHBVwas higher inHIV-infectedforeignerscomparedtoHIV-infected Italian patients.Future pathogenesisstudies are neededto confirmthehigherriskforLP,AHD,andAIDSinHBV coin-fected patients. Our dataalso confirma higherprevalence ofHIV/HCVinfectionsamongdrugaddicts,especiallyinthe 35–59agegroup,correspondingtothosebornintheyears con-sideredmostatriskfordrugabuse.Thisalsosuggeststhatthe higherperceived riskofdiseaseleadstoearlierHIVtesting comparedtoHIV/HBVpatients.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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