Total patients admitted with HIV in the clinic from January 1

(1)

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

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Original

article

Evaluation

of

late

presentation

for

HIV

treatment

in

a

reference

center

in

Belo

Horizonte,

Southeastern

Brazil,

from

2008

to

2010

Melissa

Bianchetti

Valentini

a,c,∗

,

Maria

Luíza

Guerra

de

Toledo

d

,

Marise

Oliveira

Fonseca

a,b

,

Laura

Maria

Silva

Thiersch

b

,

Ingrid

Silva

Bremer

de

Toledo

b

,

Flávia

Cristina

Jácome

Machado

b

_,

_Unaí

_Tupinambás

a,b

a_Postgraduate_Program_on_Health_Science,_Infectious_Diseases_and_Tropical_Medicine,_Universidade_Federal_de_Minas_Gerais_(UFMG),

BeloHorizonte,MG,Brazil

b_Medical_School,_Universidade_Federal_de_Minas_Gerais_(UFMG),_Belo_Horizonte,_MG,_Brazil

c_Voluntary_Counseling_and_Testing_{Site/Specialized}_Center_in_HIV_Outclinic_Patients_Care_(CTA–SAE),_Belo_Horizonte,_MG,_Brazil d_National_School_of_Statistical_{Science–Instituto}_Brasileiro_de_Geografia_e_Estatística_(IBGE),_Rio_de_Janeiro,_RJ,_Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received7November2014

Accepted30January2015

Availableonline10March2015

Keywords:

AIDS

Latepresentation

HIVinfection

CD4cellcount

a

b

s

t

r

a

c

t

Introduction:Since1996Brazilhasprovideduniversalaccesstofreeantiretroviraltherapy,

andasaconsequence,HIV/AIDSpatients’survivalratehasimproveddramatically.However,

accordingtoscientificreports,asignificantnumberofpatientsarestilllatepresentingfor

HIVtreatment,whichleadstoconsequencesbothfortheindividualandsociety.Clinicaland

immunologicalcharacteristicsofHIVpatientsnewlydiagnosedwereaccessedandfactors

associatedwithlatepresentationfortreatmentwereevaluated.

Methods:Across-sectionalstudywascarriedoutinanHIV/AIDSreferencecenterinBelo

Horizonte,MinasGerais,inSoutheasternBrazilfrom2008to2010.Operationally,patients

withlatepresentation(LP)fortreatmentwerethosewhosefirstCD4cellcountwasless

than350cells/mm3_or _presented_an_AIDS_defining_{opportunistic}_infection._Patients_with

latepresentationwithadvanceddisease(LPAD)werethosewhosefirstCD4cellcountwas

lessthan200cells/mm3_or_presented_an_AIDS_defining_{opportunistic}_infection._LP_and_LPAD

associatedriskfactorswereevaluatedusinglogisticregressionmethods.

Results:Fivehundredandtwentypatientswereincludedintheanalysis.ThemedianCD4

cellcountwas336cells/mm3_(IQR:_130–531)._Two_hundred_and_seventy-nine_patients_(53.7%)

wereclassifiedasLPand193(37.1%)asLPAD.Onaverage,75%ofthepatientspresentedwith

aviralload(VL)>10,000copies/ml.Inmultivariatelogisticregressionanalysisthefactors

associatedwithLPandLPADwereage,beingsymptomaticatfirstvisitandVL.Racewasa

factorassociatedwithLPbutnotwithLPAD.

Conclusion: TheproportionofpatientswhowerelateattendingaclinicforHIVtreatmentis

stillhigh,andeffectivestrategiestoimproveearlyHIVdetectionwithaspecialfocusonthe

vulnerablepopulationareurgentlyneeded.

∗ _{Corresponding}_author_.

E-mailaddress:melissabv@hotmail.com(M.B.Valentini).

http://dx.doi.org/10.1016/j.bjid.2015.01.005

(2)

Introduction

Since the early 1980s, after the first cases of infection

by HIV were reported in Brazil, the Brazilian government

responsetotheepidemicwasforceful.Itwasbasedonearly

diagnosis,treatmentandprevention,whichweresupported

by participation from civil society and respect for human

rights.1

In1996Brazilbecamethefirstdevelopingcountrytoensure

universalaccesstofreeantiretroviraltherapy(ARV)

guaran-teedbytheFederalLaw9313.Consequently,thesurvivalrate

amongBrazilianAIDS patientshasimproveddramatically.2

Inspiteofpreventiveefforts and actionstoearlydiagnose

the infection, many patients are still late presenting for

treatment.3–10,11

Itisestimatedthattherehasbeenadecreaseinthe

propor-tionofpatientswhopresentlatefortreatmentinBrazilover

recentyears.Accordingto surveillancedatareports29% of

patientspresentedwithCD4cellcountlessthan200cell/mm3

andatleasthalfofpatientspresentedwithaCD4cellcount

lessthan350cell/mm3_in_2012.11

It is difficult to compare the proportion of late

diag-nosis ofHIV infection in different countries and even the

trends over the years in a given country, since there are

morethan 20 criteria for this definition.12,13,14 _This_seems

to be a worldwide problem. A recent meta-analysis of 44

studiesindevelopedcountriesshowedthattheaverageCD4

cellcountinthe firstvisit fortreatmenthasnotincreased

meaningfullyinthepast20 yearsandthe majorityof

peo-plestillpresentwithCD4cellcountlessthan350cells/mm3_.

15

Latediagnosis and thus delayed treatment may impact

on the individual as well as on the society. Patients

who start ARV with low CD4 cell count present higher

morbidity and mortality and have poorer treatment

response.13

Theimpactforsocietyisthatthetreatmentforlate

diag-nosisincreasescostsforthehealthsystemintheshortand

longruns.16_In_addition,_those_who_present_for_treatment_with

moreadvanceddiseasehavehigherprobabilityof

transmis-sionsincetheydonotknowabouttheirinfectionandcannot

adoptriskreductionprecautionsorlowertheirviralloadasa

consequenceofARVtherapy.17

Abetterunderstandingoflocaldataandthefactors

associ-atedwithpatientslatepresentingfortreatmentareimportant.

Thesecouldhelpensuringpublicsurveillanceprogramsand

toprovidetargetedintervention,focusingonindividualswho

areparticularlyatrisk.

Theobjectiveofthisstudywastodescribethesocial,

demo-graphic,clinicalandimmunologicalcharacteristicsofpatients

recentlydiagnosedwithHIVinfectioninareferencecenterfor

HIV/AIDS–VoluntaryCounselingandTestingSite/Specialized

CenterinHIVOutclinicPatientCare(CTA/SAE)–inBelo

Hori-zonte,MinasGeraisstate,Brazil,from 2008to2010,and to

determinefactorsassociatedwithpatientspresentinglatefor

HIVtreatment.

Materials

and

methods

Subjectsandsettings

AllpatientswhopresentedforthefirsttimeatCTA–SAEwith

arecentHIVdiagnosisbetweenJanuary1,2008andDecember

312010wereincluded.

BeloHorizonteisoneofthemostpopulatedmetropolitan

areasinthecountryandisthecapitalcityofMinasGerais,

a state insoutheastBrazil. TheHIV detection ratesin the

city are decreasing: in June 2013 it was 27.2cases/100,000

inhabitants.11 _Between _2002, _when _the _service _was

imple-mented,and2014,about3300patientshavebeenregisteredat

CTA–SAE,ofwhich2398(72.7%)arecurrentlyusingARV.Itis

oneofthethreemainclinicsthatprovideHIVtreatmentinthe

BeloHorizontemetropolitanarea,providingcareforalmost

20%ofnewlydiagnosedHIVpatientsinthecity.

Patientswereeligibleforthestudyiftheywereover18years

old;hadhadarecentdiagnosisoftheHIVinfection(defined

asthosewhohadbeendiagnosedintheprevious12months);

had initiatedtreatmentatCTA–SAEbetween the1January

2008and31 December2010,andhad hadatleastoneCD4

cellcountoranAIDSdefiningopportunisticinfection(CDC)

registered betweenthe diagnosisandoneyearthereafter.18

ToincludeonlypatientsnewlydiagnosedwithHIVinfection,

severalcriteriawereusedtoexcludepatientswhomighthave

previouslyknownabouttheirHIVinfection,orwhohada

rou-tinescreening,asduringpregnancy.

PatientswereexcludedifregisteredatCTA–SAEformore

than oneyear afterthe firstpositive HIVtest;had no

doc-umented date for their HIV test; those tested through a

pre-natal screening; and those who had attended another

HIV/AIDSspecializedcenter.Onlypatientswithatleasttwo

visitstothecenterwereincludedinthestudy.Ethicalapproval

wasobtainedfromlocalethicalcommittees.

Studydesign

Across-sectionalstudyofahistoricalcohortwascarriedout.

All data wasretrieved from clinical chartsusing

standard-izedforms.Dataabstractedfromthechartsweredemographic

information,clinicalfeatures,laboratorydata(HIVviralload,

CD4cellcounts,serologyforsyphilis,hepatitisBandC,and

tuberculin skintestresult) and timeonARVifit had been

initiatedafterthefirstappointmentattheclinic.

Definitionsandvariablesofinterest

Latepresenters(LP)werethosepatientswhosefirstCD4cell

countwasless than 350cells/mm3 _and _had_an_AIDS

defin-ing opportunistic infection were defined aslate presenters

(LP).SubjectswhopresentedwithaCD4cellcountlessthan

200cells/mm3_or_had_an_AIDS_defining_{opportunistic}_infection

weredefinedaslatepresenterswithadvanceddisease(LPAD).

Consequently,thosepatientswhosefirstCD4cellcountwas

(3)

latepresenters(NLP).Thisdefinitionisinaccordancewitha

2011EuropeanLatePresentersConsensusDefinition.19

Thefollowingexposurevariableswereconsidered:yearof

HIVdiagnosis;ageatthetimeofHIVdiagnosis;dateofthe

firstattendancetotheclinic;gender;race;levelofeducation;

occupation;placeofresidence;bepartofaself-reportedHIV

riskgroup;HIVviralload(VL);clinicalfeatures;reasonstobe

testedforHIV; hepatitisB(HBsAgand HBcantibody)andC

serology(HCVantibody);syphilis(VDRL)andtuberculinskin

test(TST).

Patients were categorized by age of the patient at the

timeofHIVdiagnosis usingthe medianage, raceaswhite

and non-white, years ofschoolingno education (illiterate),

fewer than eight years, eight to eleven years, and more

than11years,occupationashousewife,retired,unemployed,

employed,studentandother,andplaceofresidenceasBelo

Horizonte city, Belo Horizonte metropolitan area, or other

cities.

Onlysexualexposurewasconsideredasexposurerisk

cat-egory(heterosexualmen,heterosexualwomen,andmenwho

havesexwithmen–MSM)sincetherewereonlythreepatients

(0.6%)ofinjectingdrugusers(IDU).ThedateofthefirstHIV

testwas considered as the date ofHIV diagnosis.Patients

were considered symptomatic if there were any symptom

described bythe doctor inthe clinical chart. Patients who

were symptomatic at first visit, without a defining

oppor-tunisticinfection,pneumoniaorchronicnonspecificdiarrhea,

wereclassifiedaspatientswithnon-specificsymptoms.The

reasons to be tested for HIV were categorized as: doctor

request, self request, testing in Voluntary Counseling and

Testingsites(VCT),andother.

Statisticalanalyses

Thecategoricalvariables were expressedinterms of

abso-luteandrelativefrequencies,andnumericalvariableswere

expressed as medians and interquartile ranges (IQR).

Uni-variate and multivariate analysesfor factors associatedto

LP and LPADwere performed. In univariate analysis,

cate-gorical datawas comparedusing contingencytablesand a

Chi-Squaretest;numericalvariableswerecomparedusingthe

Mann–Whitney Utest. Multivariateanalysiswasconducted

usinglogisticregressionmodelswithbackwardmanual

elim-inationofvariables.

Candidatevariables formultivariateanalysiswere those

that showed an association with LP and LPAD with a

p-value≤0.20intheunivariateanalysis.Toestimatethe

mag-nitude of the association between response variables and

LP/LPAD,oddsratio(OR)with95%confidenceintervals(95%CI)

wasused.Allp-valueslessthan0.05wereconsidered

statisti-callysignificant.Goodnessoffittestingoflogisticregression

was assessed byHosmer–Lemeshow test. Statistical

analy-seswereperformedwithSPSSsoftwareversion21(SPSSInc.,

Chicago,IL,USA).

Total patients admitted with HIV in the clinic from January 1st

2008 to December 31st₂₀₁₀

N=811

Had prior treatment in another specialized HIV service

N=205 Attended the clinic only once

N=41

Diagnosed with HIV more than one year before the first attendance to the clinic

N=31

Without date of diagnosis

N=3 _{Clinical charts not found} N=2

Diagnosed in pre-natal screening N=9

N=520

(4)

Table1–CharacteristicsofnewlydiagnosedHIV patientsatinitiationoftreatmentinCTA–SAEfrom2008 to2010.

Characteristics N=520

Malen(%) 402(77.3)

Age(y),median(IQR) 35.1(28.1–44.6)

CD4cellcount,median(IQR) 336(130–531)

LP,n(%) 279(53.7)

LPAD,n(%) 193(37.1)

Levelofeducation,n(%)a

Illiterate 13(2.5)

<8y 147(28.3)

8–11y 230(44.2)

>11y 126(24.2)

HIVRiskExposure,n(%)

Heterosexualwomen 118(22.7)

Heterosexualmen 159(30.6)

MSM 243(46.7)

Occupation,n(%)b

Housewife 21(4.0)

Retired 27(5.2)

Unemployed 32(6.2)

Employed 397(76.3)

Student 30(5.8)

Race,n(%)c

White 247(47.5)

Non-white 236(45.4)

Placeofresidence,n(%)

BeloHorizonte 404(77.7)

Metropolitanarea 93(17.9)

Other 23(4.4)

ReasonsfortheHIVtest,n(%)

Doctorrequest 260(50.0)

Patientrequest 84(16.2)

VoluntaryCounselingand Testingsites

67(12.9)

Other 109(21.0)

Timebetweenthediagnosis andfirstattendance(days), median(IQR)

47(28–76.7)

ViralLoad(copies/mL), median(IQR)

30,597(9672.5–108,901)

HBsAgpositive,n(%)d ₁₃_(2.5)

Anti-HBcpositive,n(%)e ₁₂₃_(23.7)

Anti-HCVpositive,n(%)f ₁₅_(2.9)

VDRLpositive,n(%)g ₈₁_(15.6)

Tuberculinskintest,n(%)h

Negative(<5mm) 352(67.7)

Positive(≥5mm) 39(7.5)

Attendingwithsymptoms,n (%)

238(45.8)

Non-specificsymptoms 184(35.4)

Candidaesophagitis 48(9.2) Chronicnonspecific

diarrhea

44(8.5)

Pneumonia 30(5.8)

Tuberculosis 20(3.8)

Pneumocystisjiroveci pneumonia

17(3.3)

Toxoplasmagondii encephalitis

14(2.7)

Table1–(Continued₎

Characteristics N=520

Intervalindaysbetweenfirst attendanceandARV initiation,median(IQR)

57.5(27.8–430)

Yearoffirstattendance,n(%)

2008 190(36.5)

2009 183(35.2)

2010 147(28.3)

Abbreviation:IQR,interquartilerange;LA,latepresentationtocare. a _Missing_data:_n₌₄_(0.8%).

b _Missing_data:_n₌₁₃_(2.5%).

c _Missing_data:_n₌₃₇_(7.1%).

d _Missing_data:_n₌₁₉_(3.7%).

e _Missing_data:_n₌₆₅_(12.5%).

f _Missing_data:_n₌₁₆_(3.1%).

g _Missing_data:_n₌₁₁_(2.1%).

h _Missing_data:_n₌₁₂₉_(24.8%).

Results

Atotalof811HIVinfectedpatientswereadmittedtotheclinic

betweenJanuary12008andDecember312010.Five-hundred

andtwentypatientswereeligiblefortheanalysis(Fig.1).

Themajorityofpatientsincludedweremen(77.3%)with

amedianageof35.1years(IQR28.1–44.6).Theoverallmedian

CD4cellcountwas336cells/mm3_(IQR:_130–531)._It_was_greater

amongMSM(390cells/mm3_IQR:_209–563)_than_in

heterosex-ual women (338cells/mm3 _IQR: _130–531) _and _heterosexual

men(225cell/mm3_IQR:_58–444)._Almost_70%_of_the_patients

had had at least eight years of education (n=356–68.4%).

At least 75% of them lived in Belo Horizonte city.

Three-hundredandninetysevenpatients(76.3%)wereemployed.

Two-hundredandforty-threepatients(46.7%)self-reportedas

MSMand159(30.6%)self-reportedasheterosexual.From483

patientswhoprovidedinformationabouttheirracialstatus,

51%declaredthemselvesaswhiteand49%asnon-white.CD4

cellcountwasavailablefor519patients(99.8%).Thosewhodid

nothaveaCD4countmeasurement,presentedwithanAIDS

defining opportunist infection.Viral load measurementsat

firstvisitwereavailablefor97%ofthepatients.ThemedianVL

forthewholecohortwas30,597copies/ml(IQR:9673–108,901).

HBsAg,anti-HbCandanti-HCVwerepositivein13(2.5%),123

(23.7%)and15(2.9%)patients,respectively.

Two-hundredandseventy-ninepatients(53.7%)were

clas-sifiedasLPand193(37.1%)classifiedasLPAD.Despitehavinga

CD4thresholdshigherthan350cell/mm3_and₂₀₀_cells/mm3_,

eight and twenty patients met the LP and LPAD criteria,

respectively,duetothediagnosisofanAIDSdefining

oppor-tunisticinfection.Thecharacteristicsofthecohortareshown

inTable1.

Table2showsthecharacteristicsofthe patients

accord-ing totheir baseline CD4cell countmeasurement. LP and

LPADpatientsweresignificantlyolderthanNLPpatients,had

amedianageof39.7(IQR:30.8–46.4),41.2(IQR:33.9–47)and

31.8(IQR:25.8–41.5),respectively(p<0.001).Theproportionof

MSMamongLPandLPADwas38.4%and34.2%,respectively,

(5)

Table2–ComparisonofnewHIVpatientsatinitiationoftreatmentinCTA–SAEfrom2008–2010accordingtotheir baselineCD4cellcount.

Characteristics NLP(n=241;46.3.1%) LP(n=279;53.7%) p-value¶ _LPAD₍_n₌_193;_37.1%) _p_-value§

Male,n(%) 186(77.2) 216(77.4) 0.948 149(77.2) 0.916

Female,n% 55(22.8) 63(22.6) 43(22.8)

Age(y),median(IQR) 31.8(25.8–41.5) 39.7(30.8–46.4) <0.001 41.2(33.9–47.0) <0.001

Age≤35,n(%) 154(63.9) 104(37.3) <0.001 54(28.0) <0.001

Levelofeducation,n(%)a _<0.001 _<_0.001

Illiterate 2(0.8) 11(4) 8(4.1)

<8y 49(20.3) 98(35.1) 79(40.9)

8–11y 108(44.8) 122(43.7) 75(38.9)

>11y 79(32.8) 47(16.8) 31(16.1)

HIVriskexposure,n(%) <0.001 <0.001

Heterosexualwomen 55(22.8) 63(22.6) 44(22.8)

Heterosexualmen 50(20.8) 109(39.1) 83(43.0)

MSM 136(56.4) 107(38.4) 66(34.2)

Occupation,n(%)b _0.047 _0.012

Housewife 9(3.7) 12(4.3) 9(4.7)

Retired 10(4.1) 17(6.1) 13(6.7)

Unemployed 11(4.6) 21(7.5) 14(7.3)

Employed 183(75.9) 214(76.7) 152(78.8)

Student 21(8.7) 9(3.2) 3(1.6)

Race,n(%)c _0.005 _0.004

White 132(54.8) 115(41.2) 76(39.4)

Non-white 96(39.8) 140(50.2) 99(51.3)

Placeofresidence,n(%) 0.179 0.170

BeloHorizonte 192(79.7) 212(76.0) 153(79.3)

Metropolitanarea 43(17.8) 50(17.9) 28(14.5)

Others 6(2.5) 16(5.7) 11(5.7)

ReasonsforHIVtest,n(%) <0.001 <0.001

Doctorrequest 76(31.5) 184(66.0) 142(73.6)

Patientrequest 56(23.2) 28(10.0) 19(9.8)

VoluntaryCounseling andTestingsites

44(18.3) 23(8.2) 11(5.7)

Others 64(26.1) 44(15.8) 21(10.9)

Timebetweenthe diagnosisandfirst attendance(days), median(IQR)

54(29.5–91.5) 41(27–65) 0.005 40(26–63.5) 0.004

ViralLoad(copies/mL) median(IQR)

15,600(5314–29536) 81,742(26799–271788) <0.001 116,180(45463–353826) <0.001

HBsAgpositive,n(%)d ₃_(1.2) ₁₀_(3.6) _0.099 ₈_(4.1) _0.069

Anti-HBcpositive,n(%)e ₄₈_(19.9) ₇₅_(26.9) _0.060 ₅₈_(30.1) _0.018

Anti-HCVpositive,n(%)f ₃_(1.2) ₁₂_(4.3) _0.062 ₉_(4.7) _0.039

VDRLpositive,n(%)g ₄₈_(19.9) ₃₃_(11.8) _0.015 ₂₁_(10.9) _0.012

Tuberculinskintest,n(%)h _0.831 _0.976

Negative(<5mm) 162(67.2) 190(68.1) 130(67.4)

Positive(≥5mm) 23(9.5) 16(5.7) 10(5.2)

Attendwithsymptoms,n (%)

48(19.9) 190(68.1) <0.001 160(82.9) <0.001

Intervalindaysbetween firstattendanceand ARVinitiation,median (IQR)

584(306–848) 35(17–57) <0.001 28(12–43) <0.001

Yearoffirstattendance,n (%)

0.127 0.055

2008 77(31.9) 113(40.5) 83(43.0)

(6)

Characteristics NLP(n=241;46.3.1%) LP(n=279;53.7%) p-value¶ _LPAD₍_n₌_193;_37.1%) _p_-value§

2010 72(29.9) 75(26.9) 51(26.4)

Abbreviations:NLP,notlatepresentation;LP,latepresentationtocare;LPADlatepresentationwithadvanceddisease;IQR,interquartilerange; MSM,menwhohavesexwithmen;VCT,VoluntaryCounselingandTestingsites.

a _Missing_data:_n₌₃_(1.2%)_–_NLP;_n₌₁_(0.4%)_–_LP;_n₌₀_–_LPAD. b _Missing_data:_n₌₇_(2.9%)_–_NLP;_n₌₆_(2.2%)_–_LP;_N₌₂_(1.0%)_–_LPAD. c _Missing_data:_n₌₁₃_(5.4%)_–_NLP;_n₌₂₄_(8.6%)_–_LA;_N₌₁₈_(9.3%)_–_LPAD. d_Missing_data:_n₌₁₁_(4.6%)_–_NLP;_n₌₈_(2.9)_–_LP;_N₌₄_(2.1)_–_LPAD. e _Missing_data:_n₌₂₄_(9.9%)_–_NLP;_n₌₄₁_(14.7)_–_LP;_N₌₂₉_(15.0)_–_LPAD. f _Missing_data:_n₌₁₀_(4.1%)_–_NLP;_n₌₆_(2.2)_–_LP;_N₌₅_(2.6)_–_LPAD. g _Missing_data:_n₌₇_(2.9%)_–_NLP;_n₌₄_(1.4)_–_LP;_N₌₄_(2.1)_–_LPAD. h _Missing_data:_n₌₅₆_(23.2%)_–_NLP;_n₌₇₃_(26.2)_–_LP;_N₌₅₃_(27.5)_–_LPAD.

¶_p_-value_comparing_NLP_to_LP.

§ _p_-value_comparing_NLP_to_LPAD.

ofNLPwereMSM.Ontheotherhand,theproportionof

hetero-sexualmenwashigheramongLPandLPAD.Theproportion

ofpatientswithmorethan11yearsofschoolingintheNLP

groupwastwicetheproportionamongLPandLPADgroups.

Half of the patients in the cohort were tested for HIV

becauseadoctoradvisedthemtodosoandthisproportion

increasedinLP(66.0%)andLPAD(73.6%)groupsanddecreased

amongNLP(31.5%).

ThemedianVLwasalmostsixandeightfoldhigheramong

LPandLPAD,respectively,whencomparedtoNLP.Co-infection

withhepatitisBwashigherinLPandLPADgroupsthanamong

NLPbutwithoutstatisticalsignificance(p=0.099forLPand

p=0.069forLPAD).TheproportionofpositiveHCV-antibody

washigherinLPandLPADgroupsbutwithoutstatistical

sig-nificanceforLP(p=0.06).

Themediantimebetweenthediagnosisandthefirstvisit

tothetreatmentcenterwasshorterinLPandLPADgroups

thanamongNLP.Theproportionofsymptomaticpatientsat

firstvisitwashigherinLP(68.1%)andLPAD(82.9%)groups

thaninNLP(19.9%)group.ThemostreportedAIDSdefining

opportunisticinfectionsinLPandLPADgroupswereCandida

esophagitis (n=48), Pneumocystis jiroveci pneumonia(n=17),

Toxoplasmagondiiencephalitis(n=14)andtuberculosis(n=20).

Non-AIDS defining conditionsincluded chronic nonspecific

diarrhea(n=44),bacterialpneumonia(n=24)andnonspecific

symptoms(n=142).InNLPgroup48patientsreported

symp-tomsatfirstvisit;sixhadhadabacterialpneumoniaand42

nonspecificsymptoms.

The results of univariate analysis using binary logistic

regressiontoidentifyfactorsassociatedtoLPandLPADare

showninTable3.Ageover35yearscomparedtothoseunder

35;non-white compared to white;heterosexual men

com-paredtoHSH;high VLand beingsymptomaticatfirstvisit

comparedtonon-symptomatic patientswereall associated

withLPorLPAD.

Beingretired,unemployed,oremployedwereallassociated

withLPandLPADwhencomparedtostudents.Beinga

house-wifewasassociatedtoLPADbutnotwithLP.Protectivefactors

werehavingcompleted morethan eightyearsofschooling

comparedtolessthaneightyears,nothavingdonetheHIVtest

becauseadoctorhadrequestedandhavingapositiveVDRL.

Startingcarein2009comparedtostartingcarein2008was

associatedwithlesschancetobeLPAD.

The factors associatedwith LPin the final multivariate

logisticregressionmodelwereage,race,reasonstobetested

forHIV,VL,symptomsatfirstvisit,timebetweenHIVdiagnosis

andthefirstvisit,andVDRL(Table4).Similarly,the

predic-tivefactorsforLPADwerethesameasforLPexceptraceand

reasontobetestedforHIV.FactorsassociatedwithlessLP

wereselfrequestforbeingtestedforHIVcomparedto

doc-tor’srequest,andhavingapositiveVDRL.Factorsassociated

withlessLPADwerelivinginthemetropolitanareacompared

tolivinginBeloHorizonte,andhavingapositiveVDRL.ForA

shorterintervalbetweenthefirstvisitandARVinitiationwere

associatedwithbothLPandLPAD.

Discussion

TheproportionofLP(53.7%)andLPAD(37.1%)foundinthis

studywassignificantlyelevated.Theseratesarehigh,

espe-ciallyinBrazil,whereawellrecognizedpublichealthAIDS

programisavailableforover30years.

These findings were higher than those reported by the

BrazilianHealthMinistryinrecentyears.11 _Similar_to_other

studiesinBeloHorizontecity,70%oftheLPstartedcarewith

CD4cell countless than200cells/mm3_.4,9 _The_LPAD_in_this

study was less frequentthan reported previously in other

Brazilianstudieswhichrangedfrom40.8%to61%.3,6

Compared to surveillance data for the whole HIV/AIDS

Brazilianpopulation,therewasahigherproportionofmale

subjectsaswellasMSMinthiscohort.Patientsincludedin

this cohorthad highereducationallevels thanreportedfor

theoverallBrazilianpopulation10,11_and_for_Belo_Horizonte_in

particular.4,9_The_proportion_of_each_race_did_not_differ_from

thenationaldata.

In other limited-resource regions such as in African

countries, the proportion ofLP and LPAD are higher than

that observed in this study with 70–80% presenting with

advanced disease and 50–60% with CD4 count less than

350cells/mm3_.20–22_In_Mexico_as_well_as_in_Africa_the

propor-tionofLPADwasestimatedtobe61%.23_The_proportion_of_LP

wassimilartodatafrom35countriesinEurope,24_the_United

StatesofAmerica(USA)andCanada.25

LP and LPAD patients were older and this is in

accor-dancewiththeliterature.3,6,13,24–26_This_population_might_have

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Table3–UnivariateanalysisoffactorsassociatedwithLPandLPADofnewHIVpatientswhoinitiatetreatmentin CTA–SAE2008–2010.

Variables LP LPAD

Oddsratio 95%IC p-value Oddsratio 95%IC p-value

Sex

Male 1.00 1.00

Female 0.99 0.65–1.49 0.948 1.01 0.66–1.54 0.965

Age(years)

<35 1.00 1.00

≥35 2.98 2.08–4.26 <0.001 4.27 2.90–6.28 <0.001

HIVriskexposure

Heterosexualwomen 1.46 0.94–2.26 0.095 1.59 1.00–2.55 0.051

Heterosexualmen 2.77 1.82–4.22 <0.001 2.93 1.92–4.46 0.000

MSM 1.00 1.00

Levelofeducation(years)

Illiterate 2.75 0.59–12.89 0.415 1.38 0.43–4.41 0.590

<8 1.00 1.00

8–11 0.56 0.37–0.87 0.009 0.42 0.27–0.64 <0.001

>11 0.30 0.18–0.49 <0.001 0.28 0.17–0.47 <0.001

Occupation

Housewife 3.11 0.97–9.97 0.056 6.75 1.55–29.45 0.011

Retired 3.97 1.31–11.97 0.014 8.36 2.04–34.29 0.003

Unemployed 4.45 1.53–12.97 0.006 7.00 1.76–27.89 0.006

Employed 2.73 1.22–6.11 0.015 5.58 1.67–18.72 0.005

Students 1.00 1.00

Race

White 1.00

Non-white 1.67 1.17–2.40 0.005 1.63 1.12–2.36 0.011

Placeofresidence

BeloHorizonte 1.00

Metropolitanarea 1.05 0.67–1.65 0.823 0.71 0.42–1.15 0.162

Othercities 2.42 0.93–6.30 0.071 1.64 0.69–3.88 0.259

ReasonfortheHIVtest

Doctorrequirement 1.00 1.00

Patientrequirement 0.21 0.12–0.35 <0.001 0.24 0.14–0.43 <0.001

VCT 0.22 0.12–0.38 <0.001 0.16 0.08–0.33 <0.001

Other 0.28 0.18–0.45 <0.001 0.20 0.12–0.34 <0.001

Timebetweenthediagnosis andthefirstattendance(in 10days)

0.97 0.94–1.00 0.040 0.97 0.94–1.01 0.117

VL(in10,000units/ml) 1.21 1.15–1.27 <0.001 1.10 1.07–1.12 <0.001

Symptomsatfirstattendance

No 1.00

Yes 8.53 5.73–12.86 <0.001 15.48 9.84–24.34 <0.001

Timebetweenthediagnosis andthefirstattendanceand ARVinitiation(in10days)

0.96 0.95–0.97 <0.001 0.96 0.95–0.97 <0.001

Yearoffirstattendance

2008 1.00

2009 0.68 0.46–1.02 0.061 0.62 0.41–0.93 0.021

2010 0.70 0.45–1.10 0.122 0.69 0.44–1.09 0.112

VDRL

Negative 1.00 1.00

Positive 0.53 0.33–0.86 0.010 0.54 0.32–0.92 0.024

HbsAg

Negative 1.00 1.00

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Variables LP LPAD

Anti-HCV

Negative 1.00 1.00

Positive 3.49 0.97–12.54 0.055 2.62 0.92–7.48 0.072

Abbreviations:LP,latepresentationtocare;LPAD,latepresentationwithadvanceddisease;IQR,interquartilerange;MSM,menwhohavesex withmen;VCT,VoluntaryCounselingandTestingsites;VL,viralload;ARV,antiretroviraltherapy;IC,intervalofconfidence.

generations.Beingover35yearswasassociatedwithLP(OR: 1.81 95%IC 1.05–3.12, p=0. 033) and LPAD (OR: 2.61 95%IC 1.49–4.58,p=0.001).

TheproportionofpositiveTSTinthe entirecohortwas

7.5%.AlthoughtheproportionofpositiveTSTwashigherin theNLPgroupthaninLPandLPADgroupstherewereno statis-ticaldifference(p=0.831andp=0.976,respectively).Thiscould beexplainedbythehighproportionofmissingTSTresults (24.8%).

AsshownintheBraziliansurveillancedata,sexual trans-missionisthemainrouteoftransmissionastheIDUgroup wasminimal.11

Gender was not associated with LP and LPAD.

How-ever,amongpatientsself-reportedasheterosexual, women

presentedearlierthanmen.Sixty-eightpercentof

heterosex-ual menwere LPversus 53% ofheterosexual women.This

couldbeexplainedbythefactthatBrazilianwomentake

bet-tercareoftheirhealththanmen,andseekhealthservicesfor

preventiveexamsmorefrequently.27_Heterosexual_exposure,

particularlyamongmales,iswidelycorrelatedwithlate

pre-sentationandthiscouldbeexplainedbyfeweropportunities

tobetested, astheyare notthemaintargetofcampaigns

launched bythe governmentas wellas theirown lowrisk

perception.12,13

Compared to students, being retired, unemployed or

employedwasassociatedwithLPandLPADinunivariate

anal-ysis.BeingahousewifewasassociatedtoLPADbutnotwith

LP. These associations didhold inmultivariate analysis. A

Table4–FinalModelofMultivariateRegressionoffactorsassociateswithLPanLPADofnewHIVpatientswhoinitiate treatmentinCTA–SAE2008–2010.

Variables LPa _LPADb

Age(years)

<35 1.00 1.00

≥35 1.81 1.05–3.12 0.033 2.61 1.49–4.58 <0.001

Race

White 1.00

Non-white 1.75 1.03–2.97 0.037

ReasonsforHIVtest

Doctorrequest 1.00

Selfrequest 0.44 0.20–0.97 0.043

VCT 0.47 0.22–1.02 0.057

Others 1.08 0.54–2.15 0.828

Placeofresidence

BeloHorizonte 1.00

Metropolitanarea 0.35 0.17–0.72 0.005

Othercities 0.79 0.22–2.87 0.717

VL(in10,000units/ml) 1.18 1.11–1.25 <0.001 1.06 1.04–1.09 <0.001

Symptomsatfirstattendance

No 1.00 1.00

Yes 4.23 2.32–7.69 <0.001 7.75 4.15–14.45 <0.001

Timebetweenthediagnosesand thefirstattendanceandARV initiation(in10days)

0.96 0.95–0.97 <0.001 0.97 0.96–0.98 <0.001

VDRL

Negative 1.00 1.00

Positive 0.42 0.19–0.90 0.03 0.42 0.19–0.93 0.03

Abbreviations:VCT,VoluntaryCounselingandTestingsites;VL,viralload;ARV,antiretroviraltherapy;IC,intervalofconfidence.

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possibleexplanationisthelowermedianageofthestudents

(23yearsIQR:22–29)ascomparedtothemedianageofthe

othergroups.Furthermore,theproportionofMSMamongthe

studentswereexpressive(83.3%).

MSM presented earlier to care than heterosexual men,

accordingtounivariatebutnotmultivariateanalyses,possibly

becauseonaverageheterosexualpatientswereolderthanthe

MSMgroup.Themedianageofheterosexualwomenwas42

years(IQR:33–49),39(IQR:33–47)forheterosexualmen,and

30(IQR:25–38)forMSM(p<0.001).EventhoughMSMmakeup

halftheHIVinfectedpopulation,theyareinfectedatalower

age,perceivethemselvesatriskandgettestedatanearlier

stage,HIVpreventionforthisgroupremainsachallenge.

In this study, the rates of HBsAg, anti-HBc and

anti-HCVpositive were lower than thosereported forHIV/AIDS

patientsin Africa.20 _However,_these_rates _are _four, _six_and

twofoldgreaterthantheratesreportedforthegeneral

Brazil-ianpopulation.28_The_fact_that_the_hepatitis_B_virus_has_the

same infection routes as HIV could explainthis increased

proportion.Therefore,itisimportanttoreinforcehepatitisB

vaccinationinthepopulation.

Non-whiteswasshownbeathigherriskforLPin

multi-variateanalysis.However,itshouldbepointedoutthatthe

meaneducationallevelofnon-whiteswaslowerthaninthe

white group. The proportionof non-whites with less than

eightyearsofeducationwas60.2%versus24%inthewhite

group(p<0.001).Thisfactispossiblyrelatedtodisparitiesin

accesstohealthcare,socialeconomicconditionsandaccess

toeducation.

LivingintheBeloHorizontemetropolitanareawasafactor

thatreducedLPADinmultivariateanalysispossiblybecause

60%ofthispopulationhadtheirHIVtestdoneforother

rea-sons including blood donation. To be accepted, donors be

healthysincetheyarescreenedbyadoctorbeforethe

dona-tiontakesplace.

Itisdifficulttocomparetheintervalbetweendiagnosisand

treatment,sinceinmanystudies,thefirstCD4cell

measure-mentisconsideredasthestartofcare.Inthisstudyamedian

intervalof47days(IQR:28–77)wasfoundfortheoverall

popu-lation,whichwasloweramongLP(41days)andLPAD(40days)

thaninNLPgroup(54days)andcorrelateswiththeseverityof

thediseaseandtheneedtostartARVtreatmentimmediately.

Theproportion of patients who presentedwith clinical

symptomswashighanditwasassociatedwithincreasedrisk

ofLPandLPADinmultivariateregression.Itisimportantto

stressthat32% ofLPand 18%ofLPADwere asymptomatic

atpresentation inspite ofhaving a high level ofimmune

depletion.Therefore,itisimportanttoreinforceCD4cell

mea-surementafterdiagnosis,whetherthepatientissymptomatic

ornot.Furthermore,ahighproportionofpatientshadtheir

HIVtestdonebecauseofadoctor’sreferralinLPandLPAD

groups.Thismustbeanalyzedwithcautionandcould

repre-sentalowperceptionofriskandalowknowledgeoftheHIV

disease.

SimilarresultswerefoundinastudyfromRiodeJaneiro

andBaltimore,5_where_75%_of_the_studied_population_started

treatmentwithVL>10.000copies/ml,whichindicatesahigh

potentialforHIVtransmission.AstheimpactofARVandthe

decreaseinVLareconvincinglydemonstratedanditsimpact

intransmissioniswidelyaccepted29_the_results_of_this_study

showthehighriskoftransmissionbythosesubjectsbefore

theyarediagnosed.Inthisway,enthusiasmforHIVtreatment

asapreventionmeasuretoreducetransmissionisunlikelyto

beaccomplishedunlessearlydiagnosisisimproved.

Thesefindingsarealsorelevantinclinicalsettings.Many

guidelines30,31 _have_recommended _ARV_initiation _at_higher

CD4cellcounts,butthisdiscussionisnotapplicableforthe

majorityofnewHIVpatientssincetheypresentfortreatment

withCD4thresholdsbelowtherecommendednumber.

A positive VDRL was associated with a lower chance

of presenting late fortreatment. In fact a person with an

activesymptomaticsexuallytransmitteddisease(STD)might

request ahealthservice whereearly HIVtestingisoffered.

Itisnoteworthythat65%ofthepatientswithpositiveVDRL

wereinthegroupofMSM,whichreinforcestheimportance

ofpreventioninthisgroup.InthisstudyonlypositiveVDRL

was considered and syphilis was not classified in clinical

stages.

AlthoughalowerriskofLPwasnotedin2009inunivariate

analysis,thisdidnotholdtrueinthemultivariateanalysis.In

fact,anincreaseinthemedianlevelsofCD4cellswasfound

in2009(377cell/mm3_–_IQR:_151–572)_and₂₀₁₀₍₃₇₁_cells/mm3

–IQR:164–530)comparedto2008(272cell/mm3_–_IQR:_91–489).

Nevertheless, theproportionofheterosexualmalesin2008

washigher(36.8%)thanin2009(29%)and2010(24.5%)andthis

couldbeconsideredasaconfoundingfactor.Thisdifference

intheproportionofheterosexualmenintheseyearscouldnot

beexplainedbythestudy.

Thisstudy has limitations.Asahistorical study from a

singleHIV cohort, theymay notberepresentative ofother

national or international sites, though our analysis may

provideinsightsapplicabletosuchsettings.Medicalrecords

withcompleteinformationwereanimportantpointofthis

study.Thequalityofdatacollectedhasledtoaveryfew

miss-ingvalues.

Insummarytheresultsshowthatdespitetheavailability

ofARVfreeofchargeinBrazilformorethan15yearsand

mas-sivemediacampaignsencouragingHIVtestinginthecountry,

theproportionofpatientsstartingtreatmentlateisstillhigh.

Theseresultssuggestthatrecommendationforearlier

treat-ment will havelittle impact in preventionunless effective

strategiestoincreaseuniversalHIVtestingareimplemented.

Specialfocusshouldbeplacedonthosewhoarenotperceived

tobeordonotperceivethemselvestobeatriskforHIV

infec-tion,suchaselderlypeople,non-whites,lesseducatedpeople,

andheterosexualmen.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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