Hiv Staging

8/2/2019 Hiv Staging

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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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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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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 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


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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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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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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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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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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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


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.



24/52




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.



25/52

2


Unexplainedanaemia

(


26/52




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(


27/52

2


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.


endoscopyor

bronchoscopy,orbyhistology.



28/52




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.



29/52

2


Disseminatednon-

tuberculousmycobacteria

inection.

Nopresumptiveclinical

diagnosis.

Diagnosedbynding

atypicalmycobacterial

speciesromstool,blood,

bodyfuidorotherbody

tissue,excludingthelungs.

Progressivemultiocal

leukoencephalopathy.


diagnosis.

Progressivenervoussystem

disorder(cognitivedysunction,gait/speech

disorder,visualloss,limb

weaknessandcranialnerve

palsies)togetherwith

hypodensewhitematter

lesionsonneuro-imagingor

positivepolyomavirusJC

polymerasechainreaction

oncerebrospinalfuid.

Chroniccryptosporidiosis

(withdiarrhoealastingmore

thanonemonth).


diagnosis.

Cystsidentiedonmodied

Ziehl-Nielsenstain

microscopicexaminationo

unormedstool.

Chronicisosporiasis. Nopresumptiveclinical

diagnosis.

IdenticationoIsospora.

Disseminatedmycosis

(coccidiomycosisorhistoplasmosis).


diagnosis.

Histology,antigendetection

orcultureromclinicalspecimenorbloodculture.

Recurrentnon-typhoid

Salmonellabacteraemia.


diagnosis.

Bloodculture.

Lymphoma(cerebralorB-

cellnon-Hodgkin).


diagnosis.

Histologyorelevant

specimenor,orcentral

nervoussystemtumours,

neuroimagingtechniques.

Invasivecervicalcarcinoma. Nopresumptiveclinicaldiagnosis.

Histologyorcytology.



30/52




Atypicaldisseminated

leishmaniasis.


diagnosis.

Diagnosedbyhistology

(amastigotesvisualized)or

cultureromanyappropriate

clinicalspecimen.

Symptometic

HIV-associatednephropathy.


diagnosis.

Renalbiopsy.

Symptometic

HIV-associated

cardiomyopathy.


diagnosis.

Cardiomegalyandevidence

opoorletventricular

unctionconrmedby

echocardiography.



31/52

2

CRITERIA FOR WHO CLINICAL STAGING EVENTS

Children (younger than 1 years)


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.


32/52




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.


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.



33/52

1


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.


diarrhoea.


(14daysormore)diarrhoea(looseorwaterystool,three

ormoretimesdaily),not

respondingtostandard

treatment.

Stoolsobservedand

documentedasunormed.Cultureandmicroscopy

revealnopathogens.



34/52




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.



35/52


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.


diagnosis.

ChestX-ray:bilateral

reticulonodularinterstitial

pulmonaryinltratespresent

ormorethantwomonths

withnoresponsetoantibiotic

treatmentandnootherpathogenound.Oxygen

saturationpersistently


36/52




Unexplainedanaemia(


37/52


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.


endoscopy,microscopyo

specimenromtissueor

macroscopicappearanceat

bronchoscopyorhistology.



38/52




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.



39/52


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).


diagnosis.

Histology:usually

granulomaormation.

Isolation:antigendetection

romaectedtissue;culture

ormicroscopyromclinical

specimenorbloodculture.



40/52




Disseminated

mycobacteriosis,otherthan

tuberculosis.


diagnosis.

Nonspecicclinical

symptomsincluding

progressiveweightloss,

ever,anaemia,night

sweats,atigueordiarrhoea;

pluscultureoatypical

mycobacterialspeciesrom

stool,blood,bodyfuidorotherbodytissue,excluding

thelung.

Chroniccryptosporidiosis;

(withdiarrhoea).


diagnosis.

Cystsidentiedonmodied

Ziehl-Nielsenmicroscopic

examinationounormed

stool.

ChronicIsosporiasis. Nopresumptiveclinical

diagnosis.

IdenticationoIsospora.

CerebralorB-cellnon-

Hodgkinlymphoma.


diagnosis.

Diagnosedbycentral

nervoussystem

neuroimaging;histologyo

relevantspecimen.

Progressivemultiocal

leukoencephalopathy.


diagnosis.

Progressivenervoussystem

disorder(cognitive

dysunction,gaitorspeech

disorder,visualloss,limb

weaknessandcranialnerve

palsies)togetherwith

hypodensewhitematter

lesionsonneuroimagingor

positivepolyomavirusJC

(JCV)polymerasechain

reactiononcerebrospinal

fuid.

SymptomaticHIV-

associatednephropathy.


diagnosis.

Renalbiopsy.

SymptomaticHIV-

associatedcardiomyopathy.


diagnosis.

Cardiomegalyandevidence

opoorletventricular

unctionconrmedby

echocardiography.



41/52

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


42/52



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