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The
Brazilian
Journal
of
INFECTIOUS
DISEASES
Brief
communication
Prevalence
of
hepatitis
B
and
C
infection
and
associated
factors
in
people
living
with
HIV
in
Midwestern
Brazil
Natália
Alberto
Alves
Brandão
a,
Irmtraut
Araci
Hoffmann
Pfrimer
b,
Celina
Maria
Turchi
Martelli
a,
Marília
Dalva
Turchi
a,∗aInstitutodePatologiaTropicaleSaúdePública,UniversidadeFederaldeGoiás,Goiânia,GO,Brazil bPontifíciaUniversidadeCatólicadeGoiás,Goiânia,GO,Brazil
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Articlehistory:Received16September2014 Accepted16February2015 Availableonline9March2015
Keywords: HIV Hepatitis Co-infection Prevalence
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Thisstudy aimedtoestimatetheprevalenceofinfectionbythehepatitisBvirus(HBV) andhepatitisCvirus(HCV)inpeopleinfectedbythehumanimmunodeficiencyvirus(HIV) andanalyzesociodemographicandbehavioralfactorsassociatedwithsuchco-infection.A cross-sectionstudywasperformedin495individualstreatedatapubliccenterinthecity ofGoiânia.Participantswereinterviewedandbloodcollectedforevaluationofserological andmolecularmarkersforHBVandHCV.TherateofexposuretoHBVwas33.5%(95%CI 29.4–37.9).Nineteenpatients(3.8%)werediagnosedasHBVcarriers,ofwhom68.4%were HBVDNApositive.Theprevalenceofanti-HCVwas9.7%(95%CI7.3–12.7).Genotype1awas identifiedin72.7%ofthePCRsamplespositiveforHCV.Co-infectionbyallthreeviruseswas 4.4%(95%CI2.9–6.8).Being,male,aged≥40years,historyofsexuallytransmitteddisease (STD),andhavinghomosexualpracticeswereindependentlyassociatedwiththepresence ofmarkersofHBVexposure.AhistoryofinjectabledrugsuseandSTDsshowedassociation withHCVseropositivity.Approximately50%ofparticipantswerenotawareoftheirHBVand HCVserostatus.Theresultsobtainedmaycontributetoassesstheburdenofviralhepatitis inpeoplelivingwithHIVandtoguidingpreventivemeasuresformorevulnerablegroups.
©2015ElsevierEditoraLtda.Allrightsreserved.
Introduction
Hepatitis B (HBV) and C (HCV) viruses are responsible for the most common chronic viral infections worldwide. The prevalenceofHBV andHCVinfectionishigheramong peo-ple living with the human immunodeficiency virus (HIV)
∗ Correspondingauthorat:InstitutodePatologiaTropicaleSaúdePúblicadaUniversidadeFederaldeGoiásRua235,s/n,IPTSP/UFG,Setor
Universitário,Goiânia,GO74605-050,Brazil.
E-mailaddress:marilia.turchi@gmail.com(M.D.Turchi).
comparedtothegeneralpopulationduetothecommon trans-mission routes and the overlap of behavioral risk factors for theseviruses.1 Guidelines for the clinical management
of HIV patients recommend testing for infection markers for viral hepatitis, and clinical evidence shows that co-infections are associated withworse prognosisofthe liver disease.2,3
http://dx.doi.org/10.1016/j.bjid.2015.02.001
TheinvestigationofthepresenceofHBVandHCVinHIV infected patients is importantfrom the public health per-spective to measure the resources required for prevention andtreatment.Currently,HIVinfectedpatientshavegreater longevityduetoeffectiveantiretroviralregimens aswell as moreeffectivedrugstotreathepatitisBandC.Thus, estimat-ingthemagnitudeofco-infectionindifferentpopulationsis relevant.
The prevalence of HIV-HBV or HIV-HCV co-infection presents great variation and reflects differences in the sociodemographic profile, lifestyle, and hepatitis B immu-nization coverage in different population groups. A recent systematicreviewofthenationalliteratureshowedthatthe prevalenceof HCV infection amongHIV infected individu-alsrangesfrom 3.3to82.4%.4 Itisworth notingthat most
estimates of prevalence of HIV and hepatitis B and C co-infectionswereobtainedintheSouthandSoutheastregionsof Brazil.ThisstudyaimedtoestimatetheprevalenceofHBVand HCVinfectionamongHIV-infectedindividualsandto investi-gatefactorsassociatedwithco-infectioninthestateofGoiás. Theseresultsmaycontributetoassessingtheburdenofviral hepatitisinpeoplelivingwithHIVandtoguidingpreventive measuresformorevulnerablegroups.
Methods
This cross-sectional study included HIV-infected patients, aged18yearsormore,treatedatpublichealthservicesinthe cityofGoiânia,stateofGoiás,Brazil.Theparticipantswere recruitedsequentiallyfromMarchtoMay2011untilachieving thenecessarysamplesize.Asampleof450patientswas con-sideredtobesufficienttodetectprevalenceof2,0%forHBV (anti-HBc)andHCV (anti-HCV)infection,with1%precision anda95%confidenceinterval(95%CI).
After signing the informed consent form, participants underwentastructuredinterviewtoinvestigate sociodemo-graphic,clinicandbehavioralvariablespotentiallyassociated withco-infection.Bloodwascollectedtoperformlaboratory tests. Enzymeimmunoassayswere performed (3rd genera-tion ELISA)tosearch forserological markersofhepatitisB (totalanti-HBc,HBsAg,anti-HBs)andhepatitisC(anti-HCV). HBVDNAwasassayed(PCR–RealTime)inallHBsAg-positive samples.HCVviralloadwasquantified(PCR–RealTime)in allanti-HCV-positivesamples.Weconsideredthepresenceof HCVRNAasamarkerofinfectionactivity.HCVgenotyping andsubtyping(PCR–RealTime)wereperformedforallsamples thatshoweddetectableHCVRNA.Thehistoryofantiretroviral drugusewasobtainedfromtherecordsofdistributioncenters ofthesedrugs.CD4TlymphocytesandHIV-1viralload quan-tificationvalueswereobtainedfromtherecordsoftheCentral Laboratory(LaboratórioCentral–LACEN)–Goiás.
TheprevalenceofHBV and/orHCVinfection,withtheir respective95%CI,wereestimated.Aunivariateanalysiswas performed to evaluate the relationship between outcome variables (positivefor HBV or HCV)and different exposure variables (sociodemographic and behavioral variables). The
OddsRatios(ORs)andtheirrespective95%CIwerecalculated. Thevariablesthatreachedasignificancelevellowerthan0.10 forassociationwithHBVorHCVpositivityintheunivariate
analysiswereincludedinthelogisticregressionmodel,and theadjustedORwascalculated.Inthemultivariateanalysis, asignificancelevellowerthan0.05wasestablished.The statis-ticalsoftwareSPSS15.0wasused.Theprojectwasapprovedby theEthicsandResearchCommitteeofthePontificalCatholic UniversityofGoiás.
Results
Thisstudyincluded495individuals,ofwhich366weremale (73.9%). Theage of the participants ranged from 18 to 70 years(medianageof40andinterquartilerangefrom32to47 years).Previoususeofinjectabledrugswasreportedby4.6% ofmenand0.8%ofwomen(p<0.05).Sexualintercoursewith druguserswasreportedby5.2%ofmenand14.5%ofwomen (p<0.01).Historyofbloodtransfusionandtattooswasreported by13.9%and18.8%ofindividuals,respectively,withno differ-encesbetweenmenand women.Approximatelyhalfofthe participants(n=221)reportedatleastoneepisodeofsexually transmitteddisease,mostfrequentlygonorrhea (n=95) and syphilis(n=83).ThemedianperiodsinceHIVdiagnosiswassix yearswithaninterquartilerangefromtwoto10years.Theuse ofantiretroviraltherapywasreportedby74.9%ofparticipants. The prevalences of hepatitis B and C are presented in
Table1.Thepresenceofatleastonemarkerofexposureto the hepatitisBvirus (anti-HBcand/orHBsAg)wasdetected in166participants, resultinginaprevalenceof33.5% (95% CI 29.4–37.9).Nineteen patients(3.8%;95% CI 2.4–6.0)were HBsAg-positive, of whom 13 (68.4%) were positive forHBV DNAdetection.Amongthe19HBsAg-positiveindividuals,10 (52.6%)werenotawareoftheirHBVinfection.Theprevalence ofHCVinfectionwas9.7%(95%CI7.3–12.7),and54.2%ofHCV ELISApositiveindividualswerenotawareoftheirserostatus. ForquantitativeHCVRNA,ofthe48anti-HCV-positive indi-viduals,22(45.8%)hadadetectableviralload,rangingfrom 598to6,288,232copies/mL.ThefrequencyofHCVgenotypes was86.4%forgenotype1(72.7%ofsubtype1aand9.1%of sub-type1b)and13.6%forgenotype3.Ofthe22individualswith detectable viralload forHCV,four didnotknowtheywere infected,andofthe18whoknew,11reportedbeingtreated
Table1–Prevalenceofserologicalmarkersofexposure
tohepatitisBandCvirusesin495HIV-infected
individualstreatedinapublichealthcenterofGoiânia–
Goiás.
Markersofexposure n(%) (95%CI)
HepatitisB
Anti-HBc+and/orHBsAg+ 166(33.5) (29.4–37.9)
HBsAg+ 19(3.8) (2.4–6.0)
Anti-HBc+(isolated) 40(8.1) (5.9–10.9)
Anti-HBc+andanti-HBs+ 107(21.6) (18.1–25.6)
HepatitisC
Anti-HCV 48(9.7) (7.3–12.7)
HepatitisBandCa 22(4.4) (2.9–6.8)
n,numberofcases;95%CI,95%confidenceinterval;+,positive. a HepatitisBandC=anti-HBc+and/orHBsAg+andanti-HCV+.
Table2–UnivariateanalysisoffactorsassociatedwithexposuretohepatitisB(HBV)andC(HCV)virusesin495
HIV-infectedindividualstreatedinapublichealthcenterinGoiânia–Goiás.
Riskfactors ExposuretoHBVa OR(95%CI) p ExposuretoHCVb OR(95%CI) p
Yes No Yes No Gender Male 149 217 4.5(2.6–7.8) <0.01* 35 331 0.9(0.5–1.8) 0.87 Female 17 112 13 116 Age ≥40years 102 157 1.7(1.2–2.6) <0.01* 26 233 1.1(0.6–2.0) 0.79 <40years 64 172 22 214 Education <9years 53 130 0.7(0.5–1.1) 0.10* 22 161 1.5(0.8–2.7) 0.18 ≥9years 113 199 26 286 Presenceoftatoo Yes 28 65 0.8(0.5–1.3) 0.44 12 81 1.5(0.8–3.0) 0.25 No 138 264 36 366
Historyofbloodtransfusionc
Yes 24 45 1.1(0.6–1.8) 0.84 9 60 1.5(0.7–3.2) 0.32 No 142 281 39 384 HistoryofSTDd Yes 100 121 2.6(1.8–3.8) <0.01* 34 187 3.4(1.8–6.4) <0.01* No 66 207 14 259 IDU Yes 6 12 1.0(0.4–2.7) 0.99 10 8 14.4(5.4–38.7) <0.01* No 160 317 38 439
SexwithIDUe
Yes 8 29 0.5(0.2–1.1) 0.09* 7 30 2.3(1.0–5.6) 0.06*
No 158 291 41 408
Sexualorientation
Homo/bisexual 95 91 3.5(2.4–5.2) <0.01* 14 172 0.7(0.3–1.3) 0.21
Heterosexual 71 238 34 275
TimeofHIVdiagnosisf
≥6years 86 163 1.1(0.7–1.6) 0.66 29 220 1.6(0.9–2.9) 0.14
<6years 80 165 19 226
ExposuretoHCVb
Yes 22 26 1.8(1.0–3.2) 0.06* – – – –
No 144 303 – –
OR,oddsratio;95%CI,95%confidenceinterval;p,significance(<0.10). ∗ Significant;STD,sexuallytransmitteddiseases;IDU,injectabledrugusers. a ExposuretoHBV=anti-HBc+and/orHBsAg+.
b ExposuretoHCV=anti-HCV+.
c 3individualsreportednotknowingtheirbloodtransfusionhistory. d1individualreportednotknowingifhehadahistoryofSTD.
e 9individualsreportednotknowingiftheyhadsexualintercoursewithanyIDU. f 1individualreportednotknowingthetimeofHIVdiagnosis.
forhepatitisC.Twenty-twoparticipantsshowedmarkersof exposuretohepatitis Band Cviruses, which resultedin a prevalenceofco-infectionof4.4%(95%CI2.9–6.8).
Table2presentstheresultsoftheunivariateanalysisfor factors potentially associated withmarkers ofexposure to HBV (HBsAg and/or total reactive anti-HBc) or HCV (anti-HCV).Aftermultivariateanalysis,maleindividuals(adjusted OR=2.0;95%CI1.1–3.8),ageequaltoorhigherthan40years (adjusted OR=2.4; 95% CI 1.5–3.8), reported history of sex-uallytransmitteddiseases (STDs)(adjusted OR=1.9;95%CI 1.2–2.9),andhomosexualityorbisexuality(adjustedOR=3.7; 95%CI2.2–6.3)wereindependentlyassociatedwitha signifi-cantlyhigherriskofhavingmarkersofHBVinfection.Patients
withahistoryofSTDshadalmostthreetimeshigherriskof being anti-HCVpositive (OR=2.7; 95%CI 1.4–5.4)compared withpatientswhodeniedhavingSTDs.Ahistoryofinjectable drugsusewasassociatedwithalmost12-foldtheriskofHCV infection(anti-HCVpositive)comparedwithindividualswho didnotusedrugs(OR=11.8;95%CI3.9–35.8).
Discussion
The prevalence ofco-infection with the hepatitis Band C viruseswasestimatedinapopulationofadultswitha pre-dominanceofmaleswhoseexposureroutetoHIVwasmostly
sexual.TheprevalenceofHBVcarriers(HBsAg)was3.8%and ofanti-HCV was 9.7%. These prevalences are six to seven foldhigherthantheratesfoundinapopulation-basedstudy conductedincapitalcitiesofthe Midwest.5,6 These results
indicateahighpotentialmorbidityburdeninthecomingyears duetoco-infectionwithHIVandviralhepatitis.
InBrazil,studiesconductedwithHIV-infectedindividuals havefoundprevalencesofHBsAgoranti-HBccarriers rang-ing,respectively,from3.7to27.3%orfrom38.6to55.1%.7–10
Thesedifferencesprobablyreflectthepercentageofrisk fac-torsinthestudiedgroupsandtheendemicitypatternforHBV indifferentregions.Inthisstudy,3.8%(95%CI2.4–6.0)of par-ticipantswerecarriersofthehepatitisBvirus,andHBVDNA wasdetectedinapproximately65%ofHBsAg-positivecases. SincehiddenHBVinfectionwasnotinvestigatedinthisstudy, thismayhaveunderestimatedtheprevalenceofHBV-infected individuals.11 Moreover, anegative result ofthe molecular
test does not rule out the presence of the virus because viremiamaybeundetectableortemporarilysuppresseddue toantiretroviraldrugs.TheBrazilianImmunizationProgram recommendsthatHIV-infectedindividualsshouldbe inves-tigatedforHBVinfectionandthesusceptibleonesshouldbe vaccinated.Thepresentstudywasnotdesignedtoassess vac-cinecoverageorlostopportunitiesforimmunizationagainst HBV,thereby,anti-HBswasinvestigatedonlyinanti-HBc pos-itivepatients.
RegardingthefactorsassociatedwithHBVinfectionin peo-plelivingwithHIV,theresultsofthis study areconsistent withthenationalandinternationalliterature,inwhichhigher prevalenceofHBVweredescribedinoldermaleindividuals withhomosexualpractices.Theassociationbetweenolderage groupsand HBV isawell-known and widelyobservedfact resultingfromtheincreasedriskofexposurewithtimeand thegreatervaccinationcoverageinyoungerpopulations.1,12
Lessthan5%ofparticipantsreportedahistoryofinjectable drugsuse,andtheprevalenceofHCVwas9.7%.Conversely, instudiesconductedintheSouthandSoutheastregionsof Brazil,from20 to100%ofparticipantswereinjectabledrug users (IDUs),and the percentageofindividuals co-infected withHCVreached80%.9,13 AlthoughthepercentageofIDUs
inthis sampleissmallwhencomparedwiththesestudies, theuseofinjectabledrugsstillexhibitedastrongassociation withHCV-positivity,whichisconsistentwiththeliterature. Also,theassociation betweenHCVand thehistoryofSTDs was supported by the study, which indicates the impor-tanceofthesexualtransmissionofHCVthroughunprotected sex.14,15
HCVRNAwasdetectedinapproximatelyhalfof anti-HCV-positivesamples.WeassumethattheabsenceofHCVRNAis indicativeofpreviousinfectionwitheliminationofthevirus (permanentortemporary)orrepresentsafalse-positiveresult oftheserologicaltestusedfortriage,althoughall anti-HCV-positivesampleshadbeentestedinduplicates.Similarresults were described withpercentages closeto50% detection of HCVRNA inanti-HCV-positive samplesin other studies in Brazil.16,17 In contrast, HCV RNA was detected in
approxi-mately90%ofHIV-positiveindividualswho hadneverbeen treatedforHCV13 intheSouthregion.Thevariationsinthe
proportion of HCV RNA detection in anti-HCV samples in differentstudiesprobablyreflectmethodologicaldifferences,
whichincludethedegreeofexposuretoantiretroviraldrugs indifferentpopulationgroups.
Regarding the genotypic profileof HCV, we identified a predominanceofgenotype1,followedbygenotype3.The pre-dominanceofgenotype1isconsistentwithresultsobtained invariousstudiesconductedinBrazil.13,16,18,19Genotype1has
aworsetherapeuticresponsethangenotypes2and3.2,3
Geno-type3andsubtype1ahavebeenassociatedwithtransmission in IDUs.16,17,20 Thepresence of genotype 3 in the
popula-tionstudiedcouldindicatetheimportanceofinjectabledrugs forHCVtransmissioninHIV-infectedpatients.However,the study wasnotdesignedtoanalyzetheassociationbetween genotypesandtheHCVtransmissionroute.
Itisnoteworthythat50%ofpatientswithpositive serol-ogy for HBsAg or anti-HCV reported not knowing they were infected. These results donot allow usto state that these patientshad notbeen previouslyexaminedor coun-seledregardingtheseinfectionsbecausetheywereallbeing followed-upinspecializedreferencecenters.Thispopulation mightrequireadifferentiatedapproachtominimizelossof opportunitiesfortreatmentandtransmissionreduction.
Some limitations of this study are inherent to cross-sectionalstudies,makingitdifficulttoestablishatemporal relationship between co-infections and potential exposure variables.Althoughthesamplewasnotrandom,individuals wererecruitedinthemainspecializeddiagnosispublic cen-ter,wherealmostallHIV-infectedpatientsofthemunicipality undergoperiodicteststomonitortheHIVviralloadandCD4 count.
Despite the methodological limitations mentioned, this study allowedforprevalenceestimation and delineationof theprofileofHIV-infectedpatientsco-infectedwiththe hep-atitisBandCvirusestreatedinpubliccentersofGoiás.The resultsobtainedindicatetheneedforfuturestudiesthatallow reducingtheclinicalandeconomicimpactoflong-term co-infectionsinthispopulation.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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