hiv staging
TRANSCRIPT
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WHO CASE DEFINITIONS
OF HIV FOR SURVEILLANCE
AND REVISED CLINICAL
STAGING AND IMMUNOLOGICAL
CLASSIFICATION
OF HIV-RELATED DISEASE
IN ADULTS AND CHILDREN
Strengthening health services to fght HIV/AIDSHIV/AIDS Programme
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WHO Library Cataloguing-in-Publication Data
WHO case defnitions o HIV or surveillance and revised clinical staging and immunological classifcation o HIV-related
disease in adults and children.
1.HIV inections - diagnosis. 2.HIV inections - classifcation. 3.Disease progression. 4.Epidemiologic surveillance -
standards. 5.Disease notifcation - standards. I.World Health Organization.
ISBN 978 92 4 159562 9 (NLM classifcation: WC 503.1)
World Health Organization 2007
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World Health Organization be liable or damages arising rom its use.
Printed in France
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WHO CASE DEFINITIONSOF HIV FOR SURVEILLANCE
AND REVISED CLINICAL
STAGING AND IMMUNOLOGICAL
CLASSIFICATIONOF HIV-RELATED DISEASE
IN ADULTS AND CHILDREN
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Abbreviations 4
Introduction................................................................................................................................. 5
Background................................................................................................................................. 6
SurveillanceandcasereportingorHIV...................................................................................... 7
WHOcasedenitionorHIVinection.................................. ................................... ..................... 8
WHOcasedenitionoradvancedHIV(inectionordisease)(includingAIDS)......................... 9
PrimaryHIVinection................................................................................................................. 10
ClinicalandimmunologicalclassicationorHIVandrelateddisease......................................11
Table1. WHOclinicalclassicationoestablishedHIVinection.......................................... 12
Table2. WHOimmunologicalclassicationorestablishedHIVinection............................. 15
Annex1. Presumptiveanddenitivecr iteriaorrecognizingHIV-related
clinicaleventsamongadults(15yearsorolder)andamongchildren
(youngerthan15years)withco nrmedHIVinection................................. ............. 19
Annex2. PresumptivediagnosisosevereHIVdiseaseamongHIV-seropositive
HIV-exposedchi ldren.............................. ................................... .............................. 39
Reerences................................................................................................................................. 40
CONTENTS
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WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
AbbREVIATIONS
AIDS acquiredimmunodeciencysyndrome
ART antiretroviraltherapyCD+ T-lymphocytebearingCD4receptor
CDC UnitedS tatesCenterso rDiseaseContro la ndPreventio n
DNA deoxyribonucleicacid
HIV humanimmunodeciencyvirus
PMTCT preventionomothertochildtransmission(oHIV)
RNA ribonucleicacid
WHO WorldHealthOrganization
EIA EnzymeImmunoassay
ELISA Enzyme-LinkedimmunosorbentassayS/R Test Simpleo rRapidHIVantibodytest
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INTRODUCTION
Withaviewtoacilitatingthescalingupoaccesstoantiretroviraltherapy,andinlinewitha
public health approachi, this publication outlines recent revisions WHO has made to case
denitionsorsurveillanceoHIVandtheclinicalandtheimmunologicalclassicationorHIV-
relateddisease.HIVcasedenitionsaredenedandharmonizedwiththeclinicalstagingand
immunologicalclassicationstoacilitateimprovedHIV-relatedsurveillance,tobettertrackthe
incidence, prevalenceand treatment burden oHIV inectionand toplan appropriate public
health responses. The revised clinical staging and immunological classication o HIV are
designedtoassistinclinicalmanagementoHIV,especiallywherethereislimitedlaboratory
capacity.Thenalrevisionsoutlinedherearederivedromaseriesoregionalconsultationswith
Member States in all WHO regions held throughout 2004 and 2005, comments rom public
consultationandthedeliberationsoaglobalconsensusmeetingheldinApril2006.
Inmostcountries,reportingoacquiredimmunodeciencysyndrome(AIDS)caseshasbeen
incompleteandchildrenarerarelyincluded.Further,timelyandappropriateuseoantiretroviral
therapydelaysandmaypreventthedevelopmentoAIDSaspreviouslydened.Theadvances
inantiretroviraltherapy(ART)thereoremeanthatpublichealthsurveillanceoAIDSalonedoes
not provide reliable population-based inormation on the scale and magnitude o the HIV
epidemic. Data on adults and children diagnosed with HIV inection are more useul or
determiningpopulationsneedingpreventionandtreatmentservices.
SimpliedHIVcasedenitionsareprovidedbasedonlaboratorycriteriacombinedwithclinical
orimmunologicalcriteria.TheclinicalstagingoHIV-relateddiseaseoradultsandchildrenand
thesimpliedimmunologicalclassicationareharmonizedtoauniversalour-stagesystemthat
includessimpliedstandardizeddescriptorsoclinicalstagingevents.TherevisedHIVcase
denitionsandtheclinicalandimmunologicalclassicationsystemproposedareintendedor
conductingpublichealthsurveillanceandoruseinclinicalcareservices.WHOrecommends
thatnationalprogrammesreviewandstandardizetheirHIVandAIDScasereportingandcase
denitionsinthelightotheserevisions.
i Thepublichealthapproachtoantiretroviraltherapyisdenedintheollowingarticle:TheWHOpublic-healthapproachtoan-
tiretroviraltreatmentagainstHIVinresource-limitedsettings.C Gilks, S Crowley, R Ekpini, et al. Lancet(Vol.368,August2006,
505510).
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WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
In 1986, WHO developed a provisional clinical AIDS case denition or adults and children
(Banguidenition)[1]toreportAIDScasesinresource-constrainedsettings[2, 3].Thedenition
was ormalized in 1986 and modied in 1989 (or adults and adolescents only) to include
serological HIV testing and then modied again in 1994 to accommodate 1993 revisions to
European and United States Centers or Disease Control and Prevention denitions [3-12].
European and United States Centers or Disease Control and Prevention denitions include
speciccasedenitionsorchildren.StudiesinAricansettings[13-15]suggestthattheoriginal
WHOclinicalcasedenitionsorAIDSinchildrenarenotverysensitiveorspecic.AIDScase
reportinginmiddle-andlow-incomecountrieshasbeenincompleteandovariableaccuracy,
which has hampered its utility. Underreporting and delays in notication are requent and
exacerbatedbyweakheathinormationsystemsandthelackodiagnosticcapacity.Inhigh-incomecountries, AIDS case reporting combined with active AIDS case-nding has allowed
AIDS noticatio n and AIDS specic mor tality to be monito red. However, the widespread
availability o successul antiretroviral therapy means that both new AIDS cases and AIDS
mortalityhavebeendecliningincountrieswithhighcoverageoantiretroviraltherapy.
bACkGROUND
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Thescale-uposervicesorART,preventingmother-to-childtransmissionoHIV(PMTCT)and
HIVcounsellingandtestinghasledtoanincreaseinthenumbersoadultsandchildrenbeing
tested and diagnosed with HIV inection. Accurate data are needed on adults and children
diagnosedwithHIVinectiontoacilitateestimationothetreatmentandcareburden,toplanor
eective prevention and care interventions and assess care interventions. WHO thereore
recommendsthatcountriesconsiderconductingreportingonewlydiagnosedcasesoHIV
inectioninadultsandchildren(Box1).Therequirementsorthecondentialityandsecurityo
HIVsurveillancedataarethesameasorAIDS-relatedreporting.Provider-initiatedreportingwill
be required to increase the completeness, timeliness and eciency o HIV case reporting.
Laboratory-initiatedreportingalonewillbeinsucientorreportingHIV,asothersurveillance
inormationromthehealthcareproviderormedicalrecordswillberequired.
ForthepurposesoHIVcasedenitionsorreportingandsurveillance,childrenaredenedas
youngerthan15yearsoageandadultsas15yearsorolderi.
i ForthepurposesotheUnitedNationsConventionontheRightsotheChild,achildisahumanbeingyoungerthan18years,
unlessunderthelawapplicabletothechild,majorityisattainedearlier.TheUnitedNationsGeneralAssemblydenesyouthas
people1524yearsold.AllUnitedNationsstatisticsonyoutharebasedonthisdenition,andchildrenarethereorerequently
assumedtobepeople14yearsoldandyounger.Aninantisachildrombirthuptoageoneyear.
SURVEILLANCE AND CASE REpORTING FOR HIV
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WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
WHO case definitiOn fOr HiV infectiOn
To acilitate the reporting o HIV inection, WHO recommends the ollowing:
HIV cases diagnosed and not previously reported in each country should be reported according
to a standard national case defnition. A case o HIV inection is defned as an individual with HIV
inection irrespective o clinical stage (including severe or stage 4 clinical disease, also known
as AIDS) confrmed by laboratory criteria according to country defnitions and requirements.
Countries should develop and regularly review their testing algorithms or diagnostic and
surveillance purposes.i WHO provides a simplifed HIV case defnition designed or reporting
and surveillance (Box 1).
HIV inection is diagnosed based on laboratory criteria. Clinically diagnosing suspected or
probable HIV inection by diagnosing an AIDS-defning condition or HIV at any immunologicalstage in an adult or child requires confrmation o HIV inection by the best age-appropriate test.
Further, as maternal HIV antibody transerred passively during pregnancy can persist or as long
as 18 months among children born to mothers living with HIV, positive HIV antibody test results
are difcult to interpret in younger children, and alternative methods o diagnosis are
recommended.
Box 1. WHO case defnition or HIV inection
Adults and children 1 months or older
HIV inection is diagnosed based on:
positive HIV antibody testing (rapid or laboratory-based enzyme immunoassay). This is
confrmed by a second HIV antibody test (rapid or laboratory-based enzyme
immunoassay) relying on dierent antigens or o dierent operating characteristics;
and/or;
positive virological test or HIV or its components (HIV-RNA or HIV-DNA or ultrasensitive
HIV p24 antigen) confrmed by a second virological test obtained rom a separate
determination.
Children younger than 1 months:
HIV inection is diagnosed based on:
positive virological test or HIV or its components (HIV-RNA or HIV-DNA or ultrasensitive
HIV p24 antigen) confrmed by a second virological test obtained rom a separate
determination taken more than our weeks ater birth1.
Positive HIV antibody testing is not recommended or defnitive or confrmatory
diagnosis o HIV inection in children until 18 months o age.
i Further technical inormation on algorithms or HIV testing by WHO can be ound at http://www.who.int/diagnostics_ laboratory/
evaluations/hiv/en/index.html.
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WHO case definitiOn Of adVanced HiV
(infectiOn Or disease) (including aids) fOr repOrting:
Cases diagnosed with advanced HIV inection (including AIDS) not previously reported should be
reported according to a standard case defnition. Advanced HIV inection is diagnosed based on
clinical and/or immunological (CD4) criteria among people with confrmed HIV inection (Box 2).
Box 2. Criteria or diagnosis o advanced HIV (including AIDSa)
or reporting
Clinical criteria or diagnosis o advanced HIV in adults and childrenwith confrmed HIV inection:
presumptive or defnitive diagnosis o any stage 3 or stage 4 conditionb
.
and/or;
Immunological criteria or diagnosing advanced HIV in adults andchildren fve years or older with confrmed HIV inection:
CD4 count less than 350 per mm3 o blood in an HIV-inected adult or child.
and/or;
Immunological criteria or diagnosing advanced HIV in a child younger
than fve years o age with confrmed HIV inection:
%CD4+
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10WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
ThereisnostandarddenitionoprimaryHIVinection.However,reportingprimaryHIVinection,
whererecognizedanddocumented,isuseulandshouldbeencouraged.TheUnitedStates
CentersorDiseaseControlandPrevention(CDC)areexpectedtodevelopacasedenitionor
reportingprimaryHIVinection.PrimaryHIVinectioncanberecognizedininants,children,
adolescents and adults; itcan be asymptomatic or be associated with eatureso anacute
retroviralsyndromeovariableseverity[16-21].Primaryinectionusuallypresentsasanacute
ebrileillness24weekspostexposure,otenwithlymphadenopathy,pharyngitis,maculopapular
rash, orogenital ulcers andmeningoencephalitis. Prooundtransient lymphopaenia(including
lowCD4)candevelop,andopportunisticinectionsmayoccur,buttheseinectionsshouldnot
beconusedwithclinicalstagingeventsdevelopinginestablishedHIVinection.PrimaryHIV
inectioncanbeidentiedbyrecentappearanceoHIVantibodyorbyidentiyingviralproducts(HIV-RNAorHIV-DNAand/orultrasensitiveHIVp24antigen)withnegative(orweaklyreactive)
HIVantibody[16, 22, 23].
pRIMARy HIV INFECTION
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11
Initiallyin1990,aour-stageclinicalstagingsystemwasdevelopedorclinicalpurposesand
onlyoradults[24].Subsequentlyin2002,a three-stagesystemorchildrenwasproposedto
support rolling outART [25]. This publication revises the 2003 WHO clinicalstaging oHIV-
relateddiseaseininantsandchildren,whichisnowharmonizedwiththe1990classicationo
diseaseoradultsandadolescents.Thisissimilartotheour-stageclinicalclassicationothe
UnitedStatesCDCrevisedin1994andoriginallyintendedorsurveillancepurposes [26].Both
theUnitedStatesCDCandWHOclinicalclassicationsrecognizeprimaryHIVinection.Itis
alsoproposedthattheappearanceoneworrecurrentclinicalstagingeventsorimmunodeciency
beusedtoassessindividualsoncetheyarereceivingART.
Clinical assessment prior to treatment
ClinicalstagingisusedonceHIV inectionhasbeenconrmed(serologicaland/orvirological
evidenceo HIVinection).An additionalpresumptiveclinicaldiagnosisosevereHIV disease
(equivalenttosevereimmunodeciency)amonginantsyoungerthan18monthsissuggested
oruseinsituationsinwhichdenitivevirologicaldiagnosisoHIVinectionisnotreadilyavailable
(Annex2).
The clinical events used to categorize HIV disease among inants, children, adolescents or
adultslivingwithHIVaredividedintothoseorwhichapresumptiveclinicaldiagnosismaybe
made (where syndromes or conditions can be diagnosed clinically or with basic ancillaryinvestigations) and those requiring a denitive diagnosis (generally conditions described
accordingtocausationrequiringmorecomplexorsophisticatedlaboratoryconrmation).Table
1 provides the clinical stage in simplied terms describing the spectrum o HIV related
symptomatology,asymptomatic,mildsymptoms,advancedsymptomsandseveresymptoms.
Tables3and4summarizetheclinicalstagingevents,andAnnex1providesurtherdetailsothe
speciceventsandthecriteriaorrecognizingthem.
Theclinicalstageisuseulorassessmentatbaseline(rstdiagnosisoHIVinection)orentry
intolong-termHIVcareandintheollow-upopatientsincareandtreatmentprogrammes.It
shouldbeusedtoguidedecisionsonwhentostartco-trimoxazoleprophylaxisandotherHIV-relatedinterventions,includingwhentostartantiretroviraltherapy.Theclinicalstageshavebeen
showntoberelatedtosurvival,prognosisandprogressio noclinicaldiseasewithoutantiretroviral
therapyinadultsandchildren [27-38].i
i ThroughtheconsultationprocesswithWHOMemberStates,HIVexpertshavesuggestedthat,ithreeormoreconditionsrom
anyoneclinicalstagearepresentatthesametime,theclinicalstagemaybeconsideredtobehigher.Forexample,concurrent
presenceothreeormorestage2clinicaleventswouldsuggestclinicalstage3.However,adoptingthisapproachrequires
urtherstudy.
CLINICAL AND IMMUNOLOGICAL CLASSIFICATION
OF HIV AND RELATED DISEASE
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12WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Table 1. WHO clinical staging o established HIV inection
HIV-associated symptoms WHO clinical stage
Asympto matic 1
Mildsymptoms 2
Advancedsymptoms 3
Severesymptoms 4
Clinical assessment o people receiving antiretroviral therapy
Treatment with potent and eective antiretroviral therapy regimens can reverse and improve
clinicalstatusinkeepingwithimmunerecoveryandsuppressionoviralload[37, 39-41].Newor
recurrentclinicalstagingeventsoncepeoplearereceivingantiretroviraltherapyormorethan24
weeksmaybeusedtoguidedecision-making,particularlywhentheCD4countisnotavailable.
It is assumed that the clinical staging events remain signicant among people receiving
antiretroviral therapy asthey are among children and adults beore the start oantiretroviral
therapy.Intherst24weeksostartinganantiretroviraltherapyregimen,clinicaleventsappear
largelyduetoimmunereconstitution[42-46](orthetoxicityoantiretroviraltherapy);ater24
weeks,clinicaleventsusuallyrefectimmunedeterioration.However,themonitoringodisease
progression and response to therapy using clinical staging events urgently needs to be
validated.
Immunological assessment
ThepathogenesisoHIVinectionislargelyattributabletothedecreaseinthenumberoTcells
(aspecictypeolymphocyte)thatbeartheCD4receptor(CD4+).Theimmunestatusoachild
or adult living with HIV can be assessed by measuring the absolute number (per mm3) or
percentageoCD4+cells,andthisisregardedasthestandardwaytoassessandcharacterizetheseverityoHIV-relatedimmunodeciency.ProgressivedepletionoCD4 +Tcellsisassociated
with progression oHIV disease and an increased likelihood o opportunistic inections and
otherclinicaleventsassociatedwithHIV,includingwastinganddeath[47-52].
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1
Immune status in children
TheabsoluteCD4cellcountandthe%CD4+inhealthyinantswhoarenotinectedwithHIVare
considerablyhigherthanthoseobservedinuninectedadultsandslowlydeclinetoadultvalues
bytheageoaboutsixyears.Agemustthereorebetakenintoaccountasavariableinconsidering
absoluteCD4countsor%CD4+ [50, 53-59].Amongchildrenyoungerthanveyearsoage,the
absoluteCD4counttendstovarywithinanindividualchildmorethanthe%CD4+.Currently,
thereore,themeasurementothe%CD4+isthoughttobemorevaluableinyoungerchildren i.
Absolute CD4 counts (and less so %CD4+) fuctuate within an individual and depend on
intercurrentillness,physiologicalchangesortestvariability.Measuringthetrendovertwoorthree
repeated measurements is thereore more inormative than an individual value. Not all the
equipment in use in resource-constrained settings can accurately estimate the %CD4+. The
dedicatedcytometersaredesignedtoexclusivelyperormabsoluteCD4measurementswithout
theneedorahaematologyanalyserandthereoredonotprovide%CD4+ ii.
Anyclassicationoimmunestatushastoconsiderage.The1994immunologicalclassicatio n
o the United States CDC has previously been used [60]. WHO has proposed a modied
immunological classication based on more recent analysis o the prognosis. Analysis o
prognosisrom17studiesochildrenincluding3941childrenlivingwithHIVromUnitedStates
andEuropeansettingsprovideestimationsoCD4andage-relatedriskoprogressiontoAIDS
ordeath[50].A%CD4+o35isassociatedwitha15%riskoprogressiontoAIDSinthenext12
monthsamongchildrenagedthreemonthsandan11%riskamongthosesixmonthsold.The
revisedWHOclassicationattemptstobetterrefectthisincreasedriskintheseyoungerchildren.
Basedon reanalysisothedata,thethresholdsorsevereimmunodeciencyin childrenhave
been revised [30]. For children in the WHO classication, age-related severe HIV-related
immunodeciencyisdenedasvaluesatorbelowage-relatedCD4thresholdsbelowwhich
childrenhaveagreaterthan5%chanceodiseaseprogressiontosevereclinicalevents(AIDS)
ordeathinthenext12months.Furtherresearchisurgentlyrequiredtoassesstheprognostic
signicanceandtoascertainnormalanddisease-associatedCD4levelsamongAricanand
Asia n children [61]. Note that, among children younger than one year, the immunological
categoriesdonotrefectthesameleveloriskatanygivenage;thus,achildsixmonthsoldhasahigherriskoprogressionoranygivenCD4countthanachild11monthsold.However,to
acilitate the scaling up o access to antiretroviral therapy, WHO proposes this simplied
harmonizedimmunologicalclassicationsystemoradultsandchildren.Theimmuneparameters
andthereoreclassicationimprovewithsuccessulantiretroviraltherapy(Table2) [30, 62-67].
Immune parameters can be used to monitor the response to antiretroviral therapy, and it is
hopedthattheimmunologicalclassicationwillacilitatethis.
i Tocalculatethe%CD4+,usetheollowingormula:%CD4+=(absolutecountCD4(mm3)times100)/absolutetotallymphoctye
count(mm3).
ii WHOguidanceonCD4technologyisavailableat:http://www.who.int/diagnostics_laboratory/CD4_Technical_Advice_ ENG.pd.
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1WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Immune status in adults
ThenormalabsoluteCD4countinadolescentsandadultsrangesrom500to1500cellsper
mm3oblood.Ingeneral,theCD4(%CD4+orabsolutecount)progressivelydecreasesasHIV
disease advances. As in children, individual counts may vary within an individual adult or
adolescentandassessingtheCD4countovertimeismoreuseul[68-73].TheCD4countusually
increases in response to eective combination antiretroviral therapy, although this may take
manymonths[74-78].TheproposedimmunologicalclassicationoutlinesourbandsoHIV-
relatedimmunodeciency( Table2): nosignicantimmunodeciency,mildimmunodeciency,
advanced immunodeciency and severe immunodeciency. The likelihood o disease
progression to AIDS or death without ART increases with increasing immunodeciency
(decreasingCD4)[79], opportunisticinectionsandotherHIVrelatedconditionsareincreasingly
likelywithCD4countsbelow200permm3 [29, 80, 81].ResponsetoARTisaectedbythe
immunestageatwhichitisstarted,peoplecommencingARTwithadvancedimmunodeciency
(CD4>200350permm 3)appeartohavebettervirologicaloutcomesthanthosewhocommence
withmoresevereimmunodeciency.AdultsstartingARTwithCD430amongchildrenyoungerthan12months,>25amongchildren
1235monthsor>20inchildrenover36months,orCD4count>350permm 3inadultsand
olderchildren),andtheindividualisasymptomaticoronlyhasmildsymptoms.
i WHOrecommendationsorantiretroviraltherapyoradultsandchildrenandantiretroviraldrugsorpreventingmother-to-child
transmissionhavebeenrevisedin2006.DetailsareavailableontheWHOwebsiteat:
ii Availableathttp://www.who.int/hiv/pub/guidelines/arv/en/index.html.
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1
Table 2. WHO immunological classifcation or established HIV inection
HIV-associated
immunodefciency
Age-related CD values
years(absolutenumber
per mm or%CD+)
Noneornotsignicant >35 >30 >25 >500
Mild 3035 2530 2025 350499
Advanced 25 29 20 24 1519 20 0349
Severe
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1WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Adults and adolescents iii
Clinical stage
Unexplained isevereweightloss(>10%opresumedormeasuredbodyweight)
Unexplainedchronicdiarrhoeaorlongerthanonemonth
Unexplainedpersistentever(above37.6Cintermittentorconstant,
orlongerthanonemonth)
Persistentoralcandidiasis
Oralhairyleukoplakia
Pulmonarytuberculosis(current)
Severebacterialinections(suchaspneumonia,empyema,pyomyositis, boneorjointinection,meningitisorbacteraemia)
Acutenecrotizingulcerativesto matitis,gingivitisorper iodontitis
Unexplainedanaemia(
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1
Table . WHO clinical staging o HIV/AIDS or children with confrmed HIV
inection
Clinical stage 1
Asympto matic
Persistentgeneralizedlymphadenopathy
Clinical stage 2
Unexplainedpersistenthepatosplenomegaly
Papularpruriticeruptions
Fungalnailinection
Angularcheilitis
Linealgingivalerythema
Extensivewartvirusinection
Extensivemolluscumcontagiosum
Recurrentoralulcerations
Unexplainedpersistentparotidenlargement
Herpeszoster
Recurrentorchronicupperrespiratorytractinections
(otitismedia,otorrhoea,sinusitisortonsillitis)
Clinical stage
Unexplained imoderatemalnutritionorwastingnotadequatelyrespondingtostandardtherapy
Unexplainedpersistentdiarrhoea(14daysormore)
Unexplainedpersistentever(above37.5Cintermittentorconstant,
orlongerthanonemonth)
Persistentoralcandidiasis(aterrst68weeksolie)
Oralhairyleukoplakia
Acutenecrotizingulcerativegingivi tisorperiodontitisLymphnodetuberculosis
Pulmonarytuberculosis
Severerecurrentbacterialpneumonia
Symptomaticlymphoidinterstitialpneumonitis
ChronicHIV-associatedlungdiseaseincludingbrochiectasis
Unexplainedanaemia(
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1WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Children
Clinical stage i
Unexplainedseverewasting,stuntingorseveremalnutritionnotresponding
tostandardtherapy
Pneumocystispneumonia
Recurrentseverebacterialinections(suchasempyema,pyomyositis,
boneorjointinectionormeningitisbutexcludingpneumonia)
Chronicherpessimplexinection(orolabialorcutaneousomorethanonemonths
durationorvisceralatanysite)
Oesophagealcandidiasis(orcandidiasisotrachea,bronchiorlungs)
Extrapulmonarytuberculosis
Kaposisarcoma
Cytomegalovirusinection:retinitisorcytomegalovirusinectionaectinganotherorgan,
withonsetatageolderthanonemonth
Centralnervoussystemtoxoplasmosis(ateronemontholie)
Extrapulmonarycryptococcosis(includingmeningitis)
HIVencephalopathy
Disseminatedendemicmycosis(coccidiomycosisorhistoplasmosis)
Disseminatednon-tuberculousmycobacterialinectionChroniccryptosporidiosis(withdiarrhoed)
Chronicisosporiasis
CerebralorB-cellnon-Hodgkinlymphoma
Progressivemultiocalleukoencephalopathy
SymptomaticHIV-associatednephropathyorHIV-associatedcardiomyopathy
i
i Someadditionalspecicconditionscanalsobeincludedinregionalclassications(suchasreactivationoAmericantrypano-
somiasis[meningoencephalitisand/ormyocarditis]intheWHORegionotheAmericas,disseminatedpenicilliosisinAsiaand
HIV-associatedrectovaginalstulainArica).
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1
CRITERIA FOR HIV STAGING EVENTS
Adults (1 years or older)
Clinical event Clinical diagnosis Defnitive diagnosis
Clinical stage 1
Asympto matic. NoHIV-relatedsympto ms
reportedandnosignson
examination.
Notapplicable.
Persistentgeneralized
lymphadenopathy.
Painlessenlargedlymph
nodes>1cmintwoormore
non-contiguoussites
(excludinginguinal)inthe
absenceoknowncause
andpersistingorthree
monthsormore.
Histology.
Clinical stage 2
Unexplainedmoderate
weightloss(
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20WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Recurrentoralulceration
(twoormoreepisodesin
lastsixmonths).
Aphthousulceration,
typicallypainulwithahalo
oinfammationandayellow-
greypseudomembrane.
Clinicaldiagnosis.
Papularpruriticeruption. Papularpruriticlesions,
otenwithmarkedpost-
infammatorypigmentation.
Clinicaldiagnosis.
Seborrhoeicdermatitis. Itchyscalyskincondition,
particularlyaectinghairy
areas(scalp,axillae,upper
trunkandgroin).
Clinicaldiagnosis.
Fungalnailinection. Paronychia(painulredand
swollennailbed)or
onycholysis(separationo
thenailromthenailbed)othengernails(white
discolorationespecially
involvingproximalparto
nailplatewiththickening
andseparationothenail
romthenailbed).
Fungalcultureothenailor
nailplatematerial.
Clinical stage
Unexplainedsevereweight
loss(morethan10%obody
weight).
Reportedunexplained
involuntaryweightloss
(>10%obodyweight)and
visiblethinningoace,waist
andextremitieswithobvious
wastingorbodymassindex
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21
Clinical event Clinical diagnosis Defnitive diagnosis
Unexplainedchronic
diarrhoeaorlongerthan
onemonth.
Chronicdiarrhoea(looseor
waterystoolsthreeormore
timesdaily)reportedor
longerthanonemonth.
Threeormorestools
observedanddocumented
asunormed,andtwoor
morestooltestsrevealno
pathogens.
Unexplainedpersistentever
(intermittentorconstantandlastingorlongerthanone
month).
Feverornightsweatsor
morethanonemonth,eitherintermittentorconstantwith
reportedlackoresponseto
antibioticsorantimalarial
agents,withoutother
obviousociodisease
reportedoroundon
examination;malariamustbe
excludedinmalariousareas.
Documentedever>37.5C
withnegativebloodculture,negativeZiehl-Nielsenstain,
negativemalariaslide,
normalorunchangedchest
X-rayandnootherobvious
ocusoinection.
Persistantoralcandidiasis. Persistentorrecurringcreamywhitecurd-like
plaquesthatcanbescraped
o(pseudomembranous)or
redpatchesontongue,
palateorliningomouth,
usuallypainulortender
(erythematousorm).
Clinicaldiagnosis.
Oralhairyleukoplakia. Finewhitesmalllinearor
corrugatedlesionsonlateral
bordersothetonguethat
donotscrapeo.
Clinicaldiagnosis.
Adults (1 years or older)
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22WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Pulmonarytuberculosis
(current).
Chronicsymptoms:(lasting
atleast23weeks)cough,
haemoptysis,shortnesso
breath,chestpain,weight
loss,ever,nightsweats;
PLUSEITHER
positivesputumsmear;
OR
negativesputumsmear;
AND
compatiblechestradiograph
(includingbutnotrestricted
toupperlobeinltrates,
caritation,pulmonarybrosistshrinkage.
Noevidenceo
extrapulmonarydiseas.
IsolationoM. Tuberculosis
onsputumcultureor
histologyolungbiopsy
(withcompatiblesymptoms).
Severebacterialinection
(suchaspneumonia,
meningitis,empyema,
pyomyositis,boneorjoint
inection,bacteraemiaand
severepelvicinfammatory
disease).
Feveraccompaniedby
specicsymptomsorsigns
thatlocalizeinectionand
responsetoappropriate
antibiotic.
Isolationobacteriarom
appropriateclinical
specimens(usuallysterile
sites).
Acutenecrotizingulcerative
gingivitisornecrotizing
ulcerativeperiodontitis.
Severepain,ulcerated
gingivalpapillae,loosening
oteeth,spontaneous
bleeding,badodourand
rapidlossoboneand/or
sottissue.
Clinicaldiagnosis.
Adults (1 years or older)
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2
Clinical event Clinical diagnosis Defnitive diagnosis
Unexplainedanaemia
(
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2WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Pneumocystispneumonia. Dyspnoeaonexertionor
nonproductivecougho
recentonset(withinthepast
threemonths),tachypnoea
andever;
AND
ChestX-rayevidenceo
diusebilateralinterstitial
inltrates;
AND
Noevidenceobacterial
pneumonia;bilateral
crepitationsonauscultation
withorwithoutreducedair
entry.
Cytologyor
immunofuorescent
microscopyoinduced
sputumorbronchoalveolar
lavageorhistologyolung
tissue.
Recurrentbacterial
pneumonia;
(thisepisodeplusoneor
moreepisodesinlastsix
months).
Currentepisodeplusoneor
morepreviousepisodesin
thepastsixmonths;acute
onset(
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2
Clinical event Clinical diagnosis Defnitive diagnosis
Oesophagealcandidiasis. Recentonsetoretrosternal
painordicultyon
swallowing(oodandfuids)
togetherwithoralcandidasis.
Macroscopicappearanceat
endoscopyor
bronchoscopy,orby
microscopyorhistology.
Extrapulmonarytuberculosis. Systemicillness(suchas
ever,nightsweats,
weaknessandweightloss).Otherevidenceor
extrapulmonaryor
disseminatedtuberculosis
variesbysite:
Pleural,pericardia,peritoneal
involvement,meningitis,
mediastinalorabdominal
lymphadenopathyorostetis.
DiscreteperipherallymphnodeMycobacterium
tuberculosisinection
(especiallycervical)is
consideredalesssevere
ormoextrapulmonary
tuberculosis.
M. tuberculosisisolationor
compatiblehistologyrom
appropriatesiteorradiologicalevidenceo
miliarytuberculosis;
(diuseuniormlydistributed
smallmiliaryshadowsor
micronodulesonchest
X-ray).
Ka posisarcoma. Ty picalgrossappearancein
skinororopharynxo
persistent,initiallyfat,patcheswithapinkor
violaceouscolour,skin
lesionsthatusuallydevelop
intoplaquesornodules.
Macroscopicappearanceat
endoscopyor
bronchoscopy,orbyhistology.
Adults (1 years or older)
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2WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Cytomegalovirusdisease
(otherthanliver,spleenor
lymphnode).
Retinitisonly:maybe
diagnosedbyexperienced
clinicians.Typicaleye
lesionsonundoscopic
examination:discrete
patchesoretinalwhitening
withdistinctborders,
spreadingcentriugally,
otenollowingblood
vessels,associatedwith
retinalvasculitis,
haemorrhageandnecrosis.
Compatiblehistologyor
cytomegalovirus
demonstratedin
cerebrospinalfuidby
cultureorDNA(by
polymerasechainreaction).
Centralnervoussystem
toxoplasmosis.
Recentonsetoaocal
nervoussystemabnormality
consistentwithintracranial
diseaseorreducedlevelo
consciousnessAND
responsewithin10daysto
specictherapy.
Positiveserumtoxoplasma
antibodyAND(iavailable)
singleormultipleintracranial
masslesionon
neuroimaging(computed
tomographyormagnetic
resonanceimaging).
HIVencephalopathy. Disablingcognitiveand/or
motordysunctioninterering
withactivitiesodailyliving,
progressingoverweeksor
monthsintheabsenceoa
concurrentillnessorconditionotherthanHIV
inectionthatmightexplain
thendings.
Diagnosisoexclusion:and
(iavailable)neuroimaging
(computedtomographyor
magneticresonance
imaging).
Extrapulmonary
cryptococcosis(including
meningitis).
Meningitis:usuallysubacute,
everwithincreasingsevere
headache,meningism,
conusion,behavioural
changesthatrespondto
cryptococcaltherapy.
IsolationoCryptococcus
neoformansrom
extrapulmonarysiteor
positivecryptococcal
antigenteston
cerebrospinalfuidorblood.
Adults (1 years or older)
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2
Clinical event Clinical diagnosis Defnitive diagnosis
Disseminatednon-
tuberculousmycobacteria
inection.
Nopresumptiveclinical
diagnosis.
Diagnosedbynding
atypicalmycobacterial
speciesromstool,blood,
bodyfuidorotherbody
tissue,excludingthelungs.
Progressivemultiocal
leukoencephalopathy.
Nopresumptiveclinical
diagnosis.
Progressivenervoussystem
disorder(cognitivedysunction,gait/speech
disorder,visualloss,limb
weaknessandcranialnerve
palsies)togetherwith
hypodensewhitematter
lesionsonneuro-imagingor
positivepolyomavirusJC
polymerasechainreaction
oncerebrospinalfuid.
Chroniccryptosporidiosis
(withdiarrhoealastingmore
thanonemonth).
Nopresumptiveclinical
diagnosis.
Cystsidentiedonmodied
Ziehl-Nielsenstain
microscopicexaminationo
unormedstool.
Chronicisosporiasis. Nopresumptiveclinical
diagnosis.
IdenticationoIsospora.
Disseminatedmycosis
(coccidiomycosisorhistoplasmosis).
Nopresumptiveclinical
diagnosis.
Histology,antigendetection
orcultureromclinicalspecimenorbloodculture.
Recurrentnon-typhoid
Salmonellabacteraemia.
Nopresumptiveclinical
diagnosis.
Bloodculture.
Lymphoma(cerebralorB-
cellnon-Hodgkin).
Nopresumptiveclinical
diagnosis.
Histologyorelevant
specimenor,orcentral
nervoussystemtumours,
neuroimagingtechniques.
Invasivecervicalcarcinoma. Nopresumptiveclinicaldiagnosis.
Histologyorcytology.
Adults (1 years or older)
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2WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Atypicaldisseminated
leishmaniasis.
Nopresumptiveclinical
diagnosis.
Diagnosedbyhistology
(amastigotesvisualized)or
cultureromanyappropriate
clinicalspecimen.
Symptometic
HIV-associatednephropathy.
Nopresumptiveclinical
diagnosis.
Renalbiopsy.
Symptometic
HIV-associated
cardiomyopathy.
Nopresumptiveclinical
diagnosis.
Cardiomegalyandevidence
opoorletventricular
unctionconrmedby
echocardiography.
Adults (1 years or older)
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2
CRITERIA FOR WHO CLINICAL STAGING EVENTS
Children (younger than 1 years)
Clinical event Clinical diagnosis Defnitive diagnosis
Clinical stage 1
Asympto matic. NoHIV-relatedsympto ms
reportedandnoclinical
signsonexamination.
Notapplicable.
Persistentgeneralized
lymphadenopathy.
Persistentenlargedlymph
nodes>1cmattwoormore
non-contiguoussites
(excludinginguinal)without
knowncause.
Clinicaldiagnosis.
Clinical stage 2
Unexplainedpersistent
hepatosplenomegaly.
Enlargedliverandspleen
withoutobviouscause.
Clinicaldiagnosis.
Papularpruriticeruptions. Papularpruriticvesicularlesions.
Clinicaldiagnosis.
Fungalnailinections. Fungalparonychia(painul,
redandswollennailbed)or
onycholysis(painless
separationothenailrom
thenailbed).Proximalwhite
subungualonchomycosisis
uncommonwithout
immunodeciency.
Clinicaldiagnosis.
Angularcheil itis. Splitsorcracksattheangle
othemouthnotattributable
toironorvitamindeciency,
andusuallyrespondingto
antiungaltreatment.
Clinicaldiagnosis.
Linealgingivalerythema. Erythematousbandthat
ollowsthecontourothe
reegingivalline;maybe
associatedwith
spontaneousbleeding.
Clinicaldiagnosis.
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0WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Extensivewartvirus
inection.
Characteristicwartyskin
lesions;smallfeshygrainy
bumps,otenrough,faton
soleoeet(plantarwarts);
acial,morethan5%obody
areaordisguring.
Clinicaldiagnosis.
Extensivemolluscumcontagiosuminection.
Characteristicskinlesions:smallfesh-coloured,pearly
orpink,dome-shapedor
umbilicatedgrowthsmaybe
infamedorred;acial,more
than5%obodyareaor
disguring.Giantmolluscum
mayindicatemoreadvanced
immunodeciency.
Clinicaldiagnosis.
Recurrentoralulceration. Currenteventplusatleastonepreviousepisodein
pastsixmonths.Aphthous
ulceration,typicallywitha
halooinfammationand
yellow-grey
pseudomembrane.
Clinicaldiagnosis.
Unexplainedpersistent
parotidenlargement.
Asympto maticbi lateral
swellingthatmay
spontaneouslyresolveand
recur,inabsenceoother
knowncause,usually
painless.
Clinicaldiagnosis.
Herpeszoster. Painulrashwithfuid-lled
blisters,dermatomal
distribution,canbe
haemorrhagicon
erythematousbackground,
andcanbecomelargeand
confuent.Doesnotcross
themidline.
Clinicaldiagnosis.
Children (younger than 1 years)
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1
Clinical event Clinical diagnosis Defnitive diagnosis
Recurrentorchronicupper
respiratorytractinection.
Currenteventwithatleast
oneepisodeinthepastsix
months.Symptomcomplex;
everwithunilateralace
painandnasaldischarge
(sinusitis)orpainulswollen
eardrum(otitismedia),sore
throatwithproductivecough
(bronchitis),sorethroat
(pharyngitis)andbarking
croup-likecough
(laryngotrachealbronchitis).
Persistentorrecurrentear
discharge.
Clinicaldiagnosis.
Clinical stage
Unexplainedmoderatemalnutritionorwasting.
Weightloss:lowweight-or-age,upto2standard
deviationsromthemean,
notexplainedbypooror
inadequateeedingandor
otherinections,andnot
adequatelyrespondingto
standardmanagement.
Documentedlossobodyweighto2standard
deviationsromthemean,
ailuretogainweighton
standardmanagementand
noothercauseidentied
duringinvestigation.
Unexplainedpersistent
diarrhoea.
Unexplainedpersistent
(14daysormore)diarrhoea(looseorwaterystool,three
ormoretimesdaily),not
respondingtostandard
treatment.
Stoolsobservedand
documentedasunormed.Cultureandmicroscopy
revealnopathogens.
Children (younger than 1 years)
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2WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Unexplainedpersistentever;
(>37.5Cintermittentor
constantorlongerthanone
month).
Reportsoeverornight
sweatsorlongerthanone
month,eitherintermittentor
constant,withreportedlack
oresponsetoantibioticsor
antimalarialagents.Noother
obviousociodisease
reportedoroundon
examination.Malariamustbe
excludedinmalariousareas.
Documentedevero
>37.5Cwithnegativeblood
culture,negativemalaria
slideandnormalor
unchangedchestX-rayand
nootherobviousocio
disease.
Oralcandidiasis;
(atertherst68weeks
olie).
Persistentorrecurring
creamywhitetoyellowsot
smallplaqueswhichcanbe
scrapedo
(pseudomembranous),or
redpatchesontongue,
palateorliningomouth,
usuallypainulortender
(erythematousorm).
Microscopyorculture.
Oralhairyleukoplakia. Finesmalllinearpatcheson
lateralbordersotongue,
generallybilaterally,thatdo
notscrapeo.
Clinicaldiagnosis.
Acutenecrotizingulcerative
gingivitisorstomatitis,oracutenecrotizingulcerative
periodontitis.
Severepain,ulcerated
gingivalpapillae,looseningoteeth,spontaneous
bleeding,badodour,and
rapidlossoboneand/or
sottissue.
Clinicaldiagnosis.
Lymphnodetuberculosis. Non-acute,painlesscold
enlargementoperipheral
lymphnodes,localizedto
oneregion.Responseto
standardantituberculosistreatmentinonemonth.
Histologyorneneedle
aspiratepositiveorZiehl-
Nielsenstainorculture.
Children (younger than 1 years)
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Clinical event Clinical diagnosis Defnitive diagnosis
Pulmonarytuberculosis. Nonspecicsymptoms,
suchaschroniccough,
ever,nightsweats,anorexia
andweightloss.Intheolder
childalsoproductivecough
andhaemoptysis.Historyo
contactwithadultswith
smear-positivepulmonary
tuberculosis.Noresponseto
standardbroad-spectrum
antibiotictreatment.
Oneormoresputumsmear
positiveoracid-astbacilli
and/orradiographic
abnormalitiesconsistent
withactivetuberculosisand/
orculture-positiveor
Mycobacterium.
Severerecurrentbacterial
pneumonia.
Coughwithastbreathing,
chestindrawing,nasalfaring,
wheezing,andgrunting.
Cracklesorconsolidationon
auscultation.Respondsto
courseoantibiotics.Current
episodeplusoneormorein
previoussixmonths.
Isolationobacteriarom
appropriateclinical
specimens(induced
sputum,bronchoalveolar
lavageandlungaspirate).
Symptomaticlymphocytic
interstitialpneumonia.
Nopresumptiveclinical
diagnosis.
ChestX-ray:bilateral
reticulonodularinterstitial
pulmonaryinltratespresent
ormorethantwomonths
withnoresponsetoantibiotic
treatmentandnootherpathogenound.Oxygen
saturationpersistently
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WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Unexplainedanaemia(
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Clinical event Clinical diagnosis Defnitive diagnosis
Pneumocystispneumonia. Drycough,progressive
dicultyinbreathing,
cyanosis,tachypnoeaand
ever;chestindrawingor
stridor.(Severeorvery
severepneumoniaasin
WHOIntegrated
ManagementoChildhood
Illnessguidelines.)Rapid
onsetespeciallyininants
youngerthansixmonthso
age.Responsetohigh-dose
co-trimoxazolewithor
withoutprednisolone.Chest
X-rayshowstypicalbilateral
perihilardiuseinltrates.
Cytologyor
immunofuorescent
microscopyoinduced
sputumorbronchoalveolar
lavageorhistologyolung
tissue.
Recurrentseverebacterial
inection,suchasempyema,
pyomyositis,boneorjoint
inectionormeningitisbut
excludingpneumonia.
Feveraccompaniedby
specicsymptomsorsigns
thatlocalizeinection.
Respondstoantibiotics.
Currentepisodeplusoneor
moreinprevioussixmonths.
Cultureoappropriate
clinicalspecimen.
Chronicherpessimplex
inection;(orolabialor
cutaneousomorethanonemonthsdurationorvisceral
atanysite).
Severeandprogressive
painulorolabial,genital,or
anorectallesionscausedbyherpessimplexvirus
inectionpresentormore
thanonemonth.
Cultureand/orhistology.
Oesophagealcandidiasis;
(orcandidiasisotrachea,
bronchiorlungs).
Dicultyinswallowing,or
painonswallowing(ood
andfuids).Inyoung
children,suspect
particularlyioralCandida
observedandoodreusaloccursand/ordicultyor
cryingwheneeding.
Macroscopicappearanceat
endoscopy,microscopyo
specimenromtissueor
macroscopicappearanceat
bronchoscopyorhistology.
Children (younger than 1 years)
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WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Extrapulmonarytuberculosis. Systemicillnessusuallywith
prolongedever,night
sweatsandweightloss.
Clinicaleaturesoorgans
involved,suchassterile
pyuria,pericarditis,ascites,
pleuraleusion,meningitis,
arthritis,orchitis,pericardial
orabdominal.
Positivemicroscopy
showingacid-astbacillior
cultureoMycobacterium
tuberculosisrombloodor
otherrelevantspecimen
exceptsputumor
bronchoalveolarlavage.
Biopsyandhistology.
Kaposisarcoma. Typicalappearanceinskin
ororopharynxopersistent,
initiallyfat,patcheswitha
pinkorblood-bruisecolour,
skinlesionsthatusually
developintonodules.
Macroscopieappearenceor
byhistology.
Cytomegalovirusretinitisorcytomegalovirusinection
aectinganotherorgan,with
onsetatageolderthanone
month.
Retinitisonly.
Cytomegalovirusretinitismay
bediagnosedbyexperienced
clinicians:typicaleyelesions
onserialundoscopic
examination;discretepatches
oretinalwhiteningwith
distinctborders,spreading
centriugally,otenollowing
bloodvessels,associatedwithretinalvasculitis,
haemorrhageandnecrosis.
Denitivediagnosisrequiredorothersites.Histologyor
cytomegalovirus
demonstratedin
cerebrospinalfuidby
polymerasechainreaction.
Centralnervoussystem
toxoplasmosisonsetater
ageonemonth.
Fever,headache,ocal
nervoussystemsignsand
convulsions.Usually
respondswithin10daysto
specictherapy.
Computedtomographyscan
(orotherneuroimaging)
showingsingleormultiple
lesionswithmasseector
enhancingwithcontrast.
Children (younger than 1 years)
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Clinical event Clinical diagnosis Defnitive diagnosis
Extrapulmonary
cryptococcosis(including
meningitis).
Meningitis:usually
subacute,everwith
increasingsevereheadache,
meningism,conusionand
behaviouralchangesthat
respondtocryptococcal
therapy.
Cerebrospinalfuid
microscopy(Indiainkor
Gramstain),serumor
cerebrospinalfuid
cryptococcalantigentestor
culture.
HIVencephalopathy. Atleastoneotheollowing,
progressingoveratleast
twomonthsintheabsence
oanotherillness:
ailuretoattain,orlosso,
developmentalmilestones
orlossointellectualability;
OR
progressiveimpairedbrain
growthdemonstratedby
stagnationohead
circumerence;
OR
acquiredsymmetricalmotor
decitaccompaniedbytwo
ormoreotheollowing:
paresis,pathological
refexes,ataxiaandgait
disturbances.
Neuroimaging
demonstratingatrophyand
basalgangliacalcication
andexcludingothercauses.
Disseminatedmycosis
(coccidiomycosisor
histoplasmosis).
Nopresumptiveclinical
diagnosis.
Histology:usually
granulomaormation.
Isolation:antigendetection
romaectedtissue;culture
ormicroscopyromclinical
specimenorbloodculture.
Children (younger than 1 years)
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WHO CASE DEFINITIONS OF HIV FOR SURVEILLANCE AND REVISED CLINICAL STAGING AND
IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
Clinical event Clinical diagnosis Defnitive diagnosis
Disseminated
mycobacteriosis,otherthan
tuberculosis.
Nopresumptiveclinical
diagnosis.
Nonspecicclinical
symptomsincluding
progressiveweightloss,
ever,anaemia,night
sweats,atigueordiarrhoea;
pluscultureoatypical
mycobacterialspeciesrom
stool,blood,bodyfuidorotherbodytissue,excluding
thelung.
Chroniccryptosporidiosis;
(withdiarrhoea).
Nopresumptiveclinical
diagnosis.
Cystsidentiedonmodied
Ziehl-Nielsenmicroscopic
examinationounormed
stool.
ChronicIsosporiasis. Nopresumptiveclinical
diagnosis.
IdenticationoIsospora.
CerebralorB-cellnon-
Hodgkinlymphoma.
Nopresumptiveclinical
diagnosis.
Diagnosedbycentral
nervoussystem
neuroimaging;histologyo
relevantspecimen.
Progressivemultiocal
leukoencephalopathy.
Nopresumptiveclinical
diagnosis.
Progressivenervoussystem
disorder(cognitive
dysunction,gaitorspeech
disorder,visualloss,limb
weaknessandcranialnerve
palsies)togetherwith
hypodensewhitematter
lesionsonneuroimagingor
positivepolyomavirusJC
(JCV)polymerasechain
reactiononcerebrospinal
fuid.
SymptomaticHIV-
associatednephropathy.
Nopresumptiveclinical
diagnosis.
Renalbiopsy.
SymptomaticHIV-
associatedcardiomyopathy.
Nopresumptiveclinical
diagnosis.
Cardiomegalyandevidence
opoorletventricular
unctionconrmedby
echocardiography.
Children (younger than 1 years)
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3
Clinical criteria for presumptive diagnosis of severe HIV diseaseamong infants and children aged under 1 months in situations where
virological testing is not available
A presumptive diagnosis of severe HIV disease should be made if:
the inant is confrmed as HIV antibody-positive;
and
diagnosis o any AIDS-indicator condition(s)a can be made;
or
the inant is symptomatic with two or more o the ollowing;
oral thrushb;
severe pneumoniab;
severe sepsisb.
Other factors that support the diagnosis of severe HIV disease in anHIV-seropositive infant include:
recent HIV-related maternal death or advanced HIV disease in the mother; CD4
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IMMUNOLOGICAL CLASSIFICATION OF HIV-RELATED DISEASE IN ADULTS AND CHILDREN
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