nation of HIV exposure and definitive diagnosis is critical to allow early initiation of potentially lifesaving ART [5, 1 !

"
HIV serological testing #anti$ody testing% can diagnose infection in adults and c&ildren 'ore t&an 1( 'ont&s of age" )ecause of t&e passage of 'aternal HIV anti$odies across t&e placenta to t&e $a$y, a positive HIV serological test in infancy does not confir' HIV infection in t&e infant, $ut does indicate 'aternal HIV infection and exposure of t&e infant" HIV serological tests used for clinical diagnostic testing s&ould &ave a 'ini'u' sensitivity of **+ and specificity of *(+, under standardi,ed and validated la$oratory conditions [15!" In order to diagnose HIV infection definitively in infants less t&an 1( 'ont&s of age, assays t&at detect t&e virus or its co'ponents #i"e" virological tests% are re-uired"

Virological tests t&at can $e used in infants and c&ildren include. assays to detect HIV /0A, assays to detect HIV R0A, and ultrasensitive assays to detect p1 antigen #2p1 Ag% [13!"
Assays to detect HIV /0A or HIV R0A or $ot& #collectively 4nown as nucleic acid a'plification tests [0AT!% are co''ercially availa$le using a variety of 'anual and auto'ated platfor's" 0AT tests &ave $eco'e c&eaper and easier to standardi,e, and provide several advantages for t&e early diagnosis of HIV infection in c&ildren and for 'onitoring t&e effectiveness of ART [15!" HIV virological assays used for t&e purpose of clinical diagnostic testing s&ould &ave a sensitivity of at least *5+ and a specificity of *(+ or 'ore under -uality-assured, standardi,ed and validated la$oratory conditions"

T&e sensitivity of virological tests depends in part on t&e ti'ing of t&e test" )ecause a significant proportion of HIV infection occurs in t&e peripartu' period, all virological tests are less sensitive in detecting infection on speci'ens o$tained at $irt&" HIV /0A and R0A are not detected in early $lood speci'ens $ut usually $eco'e detecta$le at or after 1 6 1 wee4s of age [13!" In infants wit& in utero HIV infection, HIV /0A and R0A can $e detected in perip&eral $lood speci'ens o$tained wit&in ( &ours of $irt&"
HIV /0A assays &ave good accuracy in w&ole $lood and /)7 in 'ost circu'stances" HIV R0A assays &ave good accuracy in plas'a and /)7, as do t&e 2p1 Ag assays" 8nly t&e newer i''une co'plex-dissociated ultrasensitive version of t&e p1 antigen assays s&ould $e used [13!"

9alse-positive and false-negative results can occur wit& virological testing, and it is necessary to confir' positive test results" :onfir'atory testing 'ay stretc& already constrained &ealt&-care sys-te's, $ut ensuring accuracy wit& confir'atory tests reduces t&e ris4 of unnecessarily starting unin-fected infants on lifelong ART" /)7 speci'ens are easiest to collect, store and process; t&ey do not re-uire venepuncture as t&ey can $e o$tained $y using $lood fro' a finger-stic4 or &eel-stic4" T&ey carry a s'aller $io&a,ard ris4 t&an li-uid sa'ples, are sta$le at roo' te'perature for prolonged periods and are easier to trans-port, allowing for centrali,ed la$oratory testing" 7peci'ens fro' /)7 can $e used for detecting HIV /0A, HIV R0A, or 2p1 Ag [13!" T&e use of /)7 is very practical for testing HIV-exposed infants in lower-level &ealt& facilities, and s&ould $e 'ore widely i'ple'ented in order to i'prove access to diagnostic testing in a range of resource-li'ited settings"
i

(1) In infants wit& a first positive virological test result, start ART wit&out delay and at t&e sa'e ti'e collect a second speci'en to confir' t&e initial positive virological test result"

1 3

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In c&ildren aged 1( 'ont&s or 'ore, HIV serological tests, including rapid serological tests #eit&er rapid HIV tests or la$oratory-$ased HIV en,y'e i''unoassays [<IAs!, or a co'$ination of $ot&%, can $e relia$ly used to diagnose HIV infection definitively in t&e sa'e 'anner as t&ey are used in adults" HIV serological testing can also $e used in infants wit& un4nown 'aternal HIV status to screen for HIV exposure and to identify infants w&o &ave seroreverted and are li4ely to $e uninfected [(!" 0ational progra''es in c&arge of >AT:T and t&e provision of ART s&ould strive to ensure t&at diagnostic protocols are in place for syste'atic testing of HIV-exposed infants and c&ildren, and sy'pto'atic infants and c&ildren w&ere HIV is suspected" T&e identification and follow-up of infants $orn to wo'en 4nown to $e HIV infected is a necessary first step in infant diagnosis" 0ational progra''es 'ay c&oose to identify &ealt&-care settings #e"g" perinatal, i''uni,ation and well c&ild clinics% w&ere routine HIV serological testing of all infants wit& un4nown HIV exposure can $e perfor'ed" T&is is es-pecially i'portant w&ere &ig& rates of HIV exposure are anticipated $ut &ave not previously $een identified for various reasons #e"g" low coverage of 'aternal antenatal care [A0:! testing, lac4 of testing facilities and ot&er infrastructure, or w&ere testing was not previously accepted $y t&e co''unity% [1(!"

It needs to $e e'p&asi,ed t&at infants and c&ildren less t&an 1( 'ont&s of age w&o are 4nown or suspected to &ave $een exposed to HIV s&ould $e closely 'onitored and s&ould $enefit early in life fro' c&ild survival interventions #nota$ly for diarr&oea and pneu'onia%, co-tri'oxa,ole prop&ylaxis [1*! and potentially ART, even w&ere virological testing is not availa$le for t&e definitive diagnosis of HIV infection"
:&ildren 'ay or 'ay not &ave a living parent or identified legal guardian, and issues of consent, co'petency to consent, disclosure, confidentiality and counselling &ave to $e considered" 0ational policies need to $e clear in t&eir reco''endations on &ow to provide HIV testing services to infants and c&ildren, and progra''es s&ould ensure t&at tools and resources provide clear specific guid-ance on counselling, infor'ed consent #fro' c&ild, parent andBor caregiver% and disclosure of HIV test results [1C-11!" If HIV infection is diagnosed in a young c&ild or infant, t&e 'ot&er &erself is usu-ally HIVinfected, and partners and ot&er si$lings 'ay also $e infected" Appropriate counselling and support s&ould t&erefore $e provided to fa'ilies w&en testing for HIV in c&ildren"

"D T&e deter'ination of HIV infection in infants and c&ildren

T&e ter' EinfantF refers specifically to a c&ild less t&an 11 'ont&s of age" All infants s&ould &ave t&eir HIV exposure status esta$lis&ed at t&eir first contact wit& t&e &ealt& syste', at or around $irt&, $ut always $efore 3 wee4s of age" T&is 'ay $e ascertained in one of t&e following ways"
ii

1. 2.

>refera$ly, $y deter'ining w&et&er t&e HIV status of t&e 'ot&er &as $een assessed in t&is preg-nancy t&roug& review of records, or 'aternal or caregiver -uestioning" If 'aternal HIV testing &as not $een done or t&e HIV status of t&e 'ot&er re'ains unclear for t&e duration of t&e pregnancy, t&en $y perfor'ing an HIV serological test on t&e 'ot&er after o$tain-ing infor'ed consent"

(2) :ountries 'ay c&oose to identify circu'stances or settings w&ere t&is reco''endation 'ay need 'odification, $ased on
HIV prevalence"

1 5

3.

If t&e 'ot&er is unavaila$le or does not consent to 'aternal HIV testing, t&en $y reco''ending HIV serological testing of t&e infant to detect HIV exposure" Aaternal or guardian consent is re--uired for suc& testing"

9or infants less t&an 3 wee4s of age wit& un4nown HIV exposure and in settings w&ere t&e HIV epi-de'ic is generali,ed #i"e" G1+ prevalence in wo'en attending A0:%, 'aternal and c&ild &ealt& #A:H% progra''es are strongly reco''ended to provide HIV serological testing to 'ot&ers or t&eir infants in order to esta$lis& exposure status"
Virological testing s&ould $e conducted at
iii,iv

6 3 wee4s of age for infants 4nown to $e exposed to HIV, or

at t&e earliest possi$le opportunity t&ereafter" Virological testing at 6 3 wee4s of age will identify 'ore t&an *5+ of infants infected in utero and intrapartu' [11-15!" 7o'e flexi$ility in i'ple'enting t&is reco''endation 'ay $e re-uired, $ased on current national or local postpartu' and infant follow-up practices" However, delaying testing $eyond t&is ti'e delays diagnosis and puts HIV-infect-ed infants at ris4 for disease progression and deat&" Results fro' virological testing in infants 'ust $e returned to t&e clinic and c&ildB'ot&erBcarer as soon as possi$le, $ut at t&e very latest wit&in four wee4s of speci'en collection" >ositive test results s&ould $e fast-trac4ed to t&e 'ot&er-$a$y pair as soon as possi$le to ena$le pro'pt initiation of ART"

@ell, HIV-exposed infants eit&er w&o &ave not &ad a virological test or &ave &ad an earlier negative virological test, are reco''ended to &ave HIV serological testing at around nine 'ont&s of age #or at t&e ti'e of t&e last i''uni,ation visit%" T&ose w&o &ave reactive serological assays at nine 'ont&s s&ould &ave a virological test to identify infected infants w&o need ART" >ositive virological testing in an infant at any age is considered indicative of HIV infection for purposes of clinical 'anage'ent, and ART is indicated #see :&apter 5%" A repeat test on a separate speci'en s&ould $e perfor'ed to confir' t&e initial positive test" T&e relia$ility of t&e la$oratory #deter'ined $y standard -uality assess'ent% is funda'ental to ensure relia$le test results [13!" 2rgent HIV diagnostic testing is reco''ended for any infant presenting to &ealt& facilities wit& signs, sy'pto's or 'edical conditions t&at could indicate HIV infection" In t&is situation, infants s&ould initially $e tested using HIV serological testing, and t&ose wit& detecta$le HIV anti$odies s&ould &ave virological testing"
9or c&ildren 11 6 1( 'ont&s of age, diagnosis using virological testing is reco''ended" However, in resource-li'ited settings w&ere access to virological testing is li'ited, it is reco''ended t&at, for t&is age group, virological tests are perfor'ed only after positive serological testing" A definitive diagnosis of HIV infection in c&ildren aged 1( 'ont&s or 'ore #wit& 4nown or un4nown HIV exposure% can $e 'ade wit& HIV serological tests, including rapid serological tests following standard testing algorit&'s used for adults #see Annex H%" T&e confir'ation of a positive serological test result s&ould follow standard national testing algorit&'s and, at a 'ini'u', s&ould involve du-

(3) :ountries 'ay wis& to deter'ine prevalence t&res&olds and ot&er circu'stances w&ere t&is reco''endation s&ould $e
followed"

(4) 0ationally or internationally approved rapid HIV serological tests 'ay $e used"

1 (

A0TIR<TR8VIRA= TH<RA>? 98R HIV I09<:TI80 I0 I09A0T7 A0/ :HI=/R<0. T8@AR/7 20IV<R7A= A::<77

plicate testing using a different HIV serological test [(!" T&e use of rapid serological tests for diagnosis &as t&e advantage t&at t&e results $eco'e availa$le at t&e ti'e of t&e clinic visit" 9or c&ildren aged 1( 'ont&s or 'ore wit& signs and sy'pto's suggestive of HIV infection, @H8 strongly reco''ends t&e use of HIV serological testing in accordance wit& national protocols" 7o'e clinical conditions are very unusual wit&out conco'itant HIV infection #e"g" >neu'ocystis pneu'o-nia, oesop&ageal candidiasis, ly'p&oid interstitial pneu'onitis, Iaposi sarco'a and cryptococcal 'eningitis%" T&e diagnosis of t&ese conditions suggests HIV infection and indicates t&e need to per-for' HIV serological testing"

"

/iagnosing HIV infection in $reastfeeding infants and c&ildren

A $reastfeeding infant or c&ild is at ris4 for ac-uiring HIV infection t&roug&out t&e entire $reastfeeding period" )reastfeeding s&ould not $e stopped in order to perfor' any 4ind of diagnostic HIV test" A positive virological test results s&ould $e considered to reflect HIV infection, and t&e usual confir'a-tory algorit&'s followed" However, interpreting negative results is difficult" A six-wee4 window period after t&e co'plete cessation of $reastfeeding is advised $efore testing; only t&en can negative viro-logical test results $e assu'ed to relia$ly indicate HIV infection status" T&is applies to $reastfeeding infants and c&ildren of all ages"

4.5 /iagnosing HIV infection w&ere 'ot&er or infant &as received ARV
drugs for >AT:T
<xisting data indicate t&at all types of virological testing can $e used fro' six wee4s of age even if t&e 'ot&er is $reastfeeding t&e c&ild and on ART" Aot&ers s&ould not discontinue t&e use of ART and s&ould not discontinue $reastfeeding for t&e purposes of testing for HIV"

4.6 >resu'ptive diagnosis of severe HIV disease in HIV-exposed infants and

c&ildren less t&an 1( 'ont&s of age
0o single clinical diagnostic algorit&' &as proved &ig&ly sensitive or specific for t&e diagnosis of HIV infection" :linical algorit&'s vary in t&eir sensitivity and specificity [13-1(!, especially wit& respect to t&e age of t&e c&ild" In particular, t&ey are less relia$le in infants [1*!" HIV serological testing #espe-cially rapid testing% and increased access to early virological testing 'ust $e 'ade availa$le to &elp clinicians i'ple'ent i'proved diagnostic algorit&'s" However, w&ere access to virological testing is not yet availa$le, a presu'ptive diagnosis of severe HIV disease can $e 'ade in infants and c&ildren w&o are less t&an 1( 'ont&s of age wit& a positive serological HIV test #in eit&er t&e 'ot&er or c&ild%, and w&o &ave specific sy'pto's suggestive of HIV infection #see section 5"3%" An infant or c&ild w&o 'eets t&ese criteria &as severe HIV disease and needs i''ediate ART" HIV serological testing s&ould $e repeated at 1( 'ont&s of age to confir' HIV infection in t&e c&ild" It s&ould $e e'p&asi,ed t&at @H8 clinical staging of HIV disease can only $e e'ployed w&ere HIV infection &as $een esta$lis&ed"
1 *

Ta$le D. 7u''ary of testing 'et&ods for infants and c&ildren

Testing 'et&odB assay HIV serology 7peci'e n typeB 'odality @&ole $lood 7creening test for HIV exposure >urpose >aediatric population for testing Infants J11 'ont&s of age

a, $

:o''ents

@ell andBor previously untested, HIVexposed infants, or infants of un4nown HIV exposure at K* 'ont&s of age

Infants of un4nown or uncertain HIV exposure w&ose 'ot&er is unavaila$le or does not consent for 'aternal testing" :onfir' reactive result wit& virological test" =ittle data exist on t&e perfor'ance of oral HIV serological assays for paediatric populations" Identifies potentially uninfected c&ild if non-reactive result and not $reastfed for at least 3 wee4s prior to test" :onduct 'aternal or infant HIV serological test for infants w&ose HIV exposure status is un4nown" :onfir' reactive result wit& virological test" If non-reactive serological test for HIV-exposed, $reastfeeding infant, repeat test 3 wee4s after co'plete cessation of $reastfeeding" If reactive result, start ART and HIV care for infant or c&ild w&o -ualifies, and confir' wit& virological test for t&ose J1( 'ont&s of age" @&ere virological testing is not availa$le, for sic4 c&ildren wit& a reactive serological test, use t&e clinical algorit&' for presu'ptive clinical diagnosis of HIV infection"

Infants or c&ildren wit& signs or sy'pto's suggestive of HIV infection

InfantsBc&ild ren G* to J1( 'ont&s of age

/iagnostic

:&ildren G1( 'ont&s of age

:onfir' reactive result wit& virological test" 9or $reastfeeding infantBc&ild w&o is HIV exposed wit& non-reactive test result, repeat test 3 wee4s after co'plete cessation of $reastfeeding" T&e nationally defined serial 1- or Dtest algorit&' s&ould $e followed"

1 C

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Testing 'et&odB assay

7peci'e n typeB 'odality @&ole $loodB li-uid @&ole $loodB /)7 >las'aBliuid

>urpose

>aediatric population for testing

:o''ents

HIV /0A

/iagnostic

Infants and c&ildren Infants and c&ildren Infants and c&ildren

HIV /0A

/iagnostic

:onfir' reactive result wit& a second virological test" :onfir' reactive result wit& a second virological test" <xercise caution in interpreting negative results if infant is esta$lis&ed on ART" :onfir' reactive result wit& a second virological test" <xercise caution in interpreting negative results if infant is esta$lis&ed on ART" :onfir' reactive result wit& a second virological test" 2se ot&er virological test in regions w&ere su$type / is co''on or if infant is already on ART" :onfir' reactive result wit& second virological test" 2se ot&er virological test in regions w&ere su$type / is co''on or if infant is already on ART" :onfir' reactive result wit& second virological test"

HIV R0A

/iagnostic

HIV R0A

@&ole $loodB /)7

/iagnostic

Infants and c&ildren

2p1 Ag

>las'aBliuid

/iagnostic

Infants and c&ildren

2p1 Ag

@&ole $loodB /)7

/iagnostic

Infants and c&ildren

1 2

In c&ildren less t&an 1( 'ont&s of age, HIV infection is diagnosed $ased on. 6 positive virological test for HIV or its co'ponents #HIV R0A or HIV /0A or 2p1 Ag% 6 confir'ed $y a second virological test o$tained fro' a separate deter'ination ta4en 'ore t&an four wee4s after $irt&" Virological testing for infants re-uires t&at test results $e returned to t&e clinic and t&e c&ildB'ot&erBcaregiver as soon as pos-si$le and, at t&e latest, wit&in four wee4s of speci'en collection" >ositive results s&ould $e fast-trac4ed to t&e 'ot&er 6 $a$y pair as soon as possi$le to ena$le pro'pt initiation of ART"

1 1

WHEN TO START ANTIRETROVIRAL THERAPY IN INFANTS AND CHILDREN

5"1 Reco''endations
5"1"1 Infants
1" Initiate ART for all HIV-infected infants diagnosed in t&e first year of life, irrespective of :/ count or @H8 clinical stage" (Strong recommendation, moderate quality of evidence)

5"1"1 :&ildren

2.

Initiate ART for all HIV-infected c&ildren $etween 11 and 1 'ont&s of age irrespective of :/ count or @H8 clinical stage" (Conditional recommendation, very low quality of evidence)

3.

Initiate ART for all HIV-infected c&ildren $etween 1 and 5* 'ont&s of age wit& :/ count L55C cellsB'' or +:/ M L15, w&ic&ever is lower, irrespective of @H8 clinical stage" (Strong recommendation, very low quality of evidence)
D

4.

Initiate ART for all HIV-infected c&ildren 'ore t&an 5 years of age wit& :/ D cellsB'' #as in adults%, irrespective of @H8 clinical stage" (Strong recommendation, moderate quality of evidence)

count LD5C

5.

Initiate ART for all HIV-infected c&ildren wit& @H8 HIV clinical stages D and , irrespective of :/ count" (Strong recommendation, low quality of evidence)

6.

Initiate ART for any c&ild less t&an 1( 'ont&s of age w&o &as $een given a presu'ptive clinical diagnosis of HIV infection" (Strong recommendation, low quality of evidence)

:urrent researc& de'onstrates t&at t&e initiation of ART early in infancy and c&ild&ood dra'atically reduces t&e ris4 of deat& and disease progression [5, 11!" @it&out effective treat'ent, an esti'ated one t&ird of infected infants will &ave died $y one year of age, and a$out &alf will &ave died $y two years of age [DC, D1!" Niven t&ese data, @H8 &as updated t&e reco''endations on w&en to $egin ART"

Ta$le . <xplanation of age ter'inology used in t&ese reco''endations

Ter' Infant 2nder 11 'ont&s of age 11 'ont&s of age or older Age 5 and over O O O O /efinition J11 'ont&s of age J11 'ont&s of age P11 'ont&s of age G5* 'ont&s of age

7tarting ART in infants is reco''ended w&en HIV infection is diagnosed [5!" 9or c&ildren 1 'ont&s of age and older, deter'ining w&en to initiate ART relies on clinical andBor i''unological assess-

1 1

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'ent [D1, DD!" 9or c&ildren aged 11 to 1 'ont&s, t&e guidelines 'a4e a conditional reco''endation to initiate ART irrespective of :/ count or @H8 clinical stage" 0ational aut&orities need to consider w&et&er i'ple'enting t&is reco''endation is li4ely to lead to $etter &ealt& outco'es for 'ost HIV-infected c&ildren" /espite t&e lac4 of &ig& -uality evidence, t&e guideline panel felt t&at t&e $enefits of adopting t&is approac& outweig& t&e ris4s 6 especially w&ere access to :/ testing is li'ited and rates of c&ild 'ortality are &ig&"
/eciding w&en to start ART s&ould also consider t&e c&ildQs social environ'ent, including t&e identification of a clearly defined caregiver w&o understands t&e prognosis of HIV and t&e i'plications of ART #i"e" lifelong t&erapy, conse-uences of non-ad&erence, and t&e ad'inistration, toxicities and storage of drugs%" Also, identifying a secondary #$ac4-up%, infor'ed caregiver is advised" Access to ade-uate nutrition #see :&apter 1 % and support for fa'ilies is e-ually i'portant" Infor'ing older c&ildren of t&eir diagnosis of HIV i'proves ad&erence" /isclosure to fa'ily 'e'$ers 'ay i'prove ad&erence and s&ould $e encouraged [D -D3!" Infor'ing c&ildren and disclosing t&eir HIV status to t&e' is a process $est perfor'ed wit& support fro' s4illed &ealt& professionals #see :&apter 13%"

5"1 @&en to initiate ART in HIV-infected infants

All infants wit& confir'ed HIV infection s&ould $e started on ART, irrespective of t&e clinical or i''unological stage" @&ere viral testing is not availa$le, infants less t&an 11 'ont&s of age wit& clinically diagnosed, pre-su'ptive severe HIV infection s&ould start ART as soon as possi$le" :onfir'ation of HIV infection s&ould $e o$tained as soon as possi$le" )y two years of age, over &alf of HIV-infected c&ildren will die in t&e a$sence of treat'ent [DC, D1, D5, D(!" Recent studies de'onstrated t&at 'ore t&an (C+ of infected infants $eco'e eligi$le to start ART $efore six 'ont&s of age w&en using t&e 1CC3 clinical andBor i''unological criteria for t&e ini-tiation of treat'ent [1D!" 7tarting asy'pto'atic infants on ART as soon as possi$le after diagnosis leads to a reduction in 'ortality co'pared wit& t&ose in w&o' treat'ent initiation is delayed until i''unological decline or clinical sy'pto's develop [5!"

5.3 @&en to initiate ART in HIV-infected c&ildren 11

'ont&s of age and older
9or c&ildren aged 11 to 1 'ont&s, t&ese guidelines offer a conditional reco''endation to initiate ART irrespective of i''unological or clinical stage" Alt&oug& no rando'i,ed trials support t&is reco''endation, a nu'$er of studies &ave s&own t&at t&e esti'ated ris4 of 'ortality is significantly &ig&er for HIV-infected c&ildren under 1 years of age [D1, D*, C!" 9urt&er'ore, a syste'atic review contrasting disease progression in HIV-infected c&ildren in su$-7a&aran Africa and t&e 27A and <urope de'onstrates t&at 'ortality rates in t&e first two years of life are &ig&er for African c&ildren, and t&at for any given :/ count or viral load #V=% African co&orts &ave worse &ealt& outco'es [ 1!" )ased on t&ese considerations t&e guideline panel concluded t&at w&ere access to i''unological testing is li'ited, and t&e $urden of paediatric HIV disease is &ig&, si'plifying eligi$ility criteria for

1 D

initiation of ART 'ay significantly i'prove &ealt& outco'es for HIV-infected c&ildren" 0ational progra''es need to deter'ine &ow $est to i'ple'ent t&is reco''endation, and w&et&er to advocate universal treat'ent for all J1 'ont&s or focus on universal treat'ent for infants J11 'ont&s and apply clinical and i''unological criteria for c&ildren $etween 11 and 1 'ont&s" 9or all c&ildren 1 'ont&s or older, clinical and i''unological t&res&olds s&ould $e used to identify t&ose w&o need to start ART"

5"

:linical criteria to start ART

T&e @H8 clinical staging of HIV/AIDS for c ildren wit esta!lis ed HIV infection #see Annex :% is consistent wit& t&e adult clinical classification syste' #Ta$le 5%" :linical staging s&ould $e used once HIV infection &as $een confir'ed #i"e" once t&ere is serological andBor virological evidence of HIV infection%"

Ta$le 5" @H8 classification of HIV-associated clinical diseaseR

:lassification of HIV-associated clinical disease Asy'pto'atic Aild Advanced 7evere

@H8 clinical stage 1 1 D

R Annexes : and / provides furt&er details on staging events and criteria for recogni,ing t&e'"

A preli'inary analysis of t&e revised @H8 staging, $ased on clinical signs at $aseline and disease &istory, in c&ildren enrolled in t&e :&ildren wit& HIV Anti$iotic >rop&ylaxis #:HA>% trial [ 1! s&owed t&at clinical staging in c&ildren not on ART is predictive of 'ortality ris4 [ D!" T&e clinical stage is t&erefore useful to identify w&en to start ART #Ta$le 5%" However, clinical staging is not as useful in infants and c&ildren less t&an two years of age" Asy'pto'atic or 'ildly sy'pto'atic HIV-infected c&ildren #i"e" t&ose wit& clinical stages 1 and 1 disease% s&ould $e considered for ART w&en i''unological values fall near t&e descri$ed t&res&old values" A drop $elow t&res&old values s&ould $e avoided" Treat'ent wit& a potent and efficient ARV regi'en i'proves clinical status and effectively reverses t&e clinical stage" It is recogni,ed, &owever, t&at reliance solely on clinical criteria 'ay inappropri-ately delay t&e initiation of ART"
i

5"5 I''unological criteria to start ART

T&e i''unological para'eters of t&e HIV-infected c&ild of 1 'ont&s of age and older s&ould $e 'easured in order to assess t&e severity of HIV-related i''unodeficiency and to guide decision-

(1) :onfir'ed weig&t-for-age and &ae'oglo$in levels were also predictive of 'ortality in HIV-infected c&ildren" T&e ti'ing of
t&e initiation of ART in relation to interventions to prevent or treat 'alnutrition and anae'ia re-uires furt&er study"

A0TIR<TR8VIRA= TH<RA>? 98R HIV I09<:TI80 I0 I09A0T7 A0/ :HI=/R<0. T8@AR/7 20IV<R7A= A::<77

'a4ing on t&e initiation of ART" T&e results of :/ 'easure'ent s&ould $e used in conSunction wit& clinical assess'ent" T&e :/ t&res&old for starting treat'ent in 1 to 5-year-olds &as c&anged" All c&ildren 1 to 5 years of age wit& +:/ M L15 or :/ a$solute count of L55C D cellsB'' are eligi$le for ART #Ta$le 3%"
:/ levels in &ealt&y infants w&o are not infected wit& HIV are considera$ly &ig&er t&an t&ose o$served in uninfected adults, and slowly decline to adult values $y t&e age of a$out five to six years of age" A$solute :/ count is naturally less constant and 'ore age-dependent t&an percent :/ M #+:/ M% in younger c&ildren #i"e" J5 years%" T&erefore, it is not possi$le to define a single t&res&old for w&en to start ART" :/ 'easure'ents are valua$le for 'a4ing decisions a$out starting t&erapy and @H8 encourages national progra''es to increase access to :/ 'easure'ent tec&nologies"

7erial 'easure'ents are 'ore infor'ative t&an individual values and also reflect trends over ti'e" @&ere possi$le, t&ese 'easure'ents s&ould co'pare t&e sa'e para'eter; i"e" eit&er a$solute :/ count or, in c&ildren less t&an 5 years of age, percent :/ M" As wit& clinical status, i''unological recovery occurs wit& successful ART; t&us, :/ 'easure'ents are useful for 'onitoring response to treat'ent"
T&e :/ levels t&at identify t&res&olds for w&en to start ART are derived fro' longitudinal data on HIVinfected infants and c&ildren and, except in c&ildren less t&an 1 'ont&s of age, correspond to a 11'ont& 'ortality ris4 of up to 5+ [D*!" It s&ould $e noted t&at t&e younger t&e c&ild, t&e less predictive t&e +:/ M or a$solute :/ count of 'ortality" In infants and c&ildren less t&an two years of age, t&ere is a &ig& ris4 of deat&, even at a &ig& :/ levels #e"g" G1 5CC cellsB'' or +:/ M G15%" T&e availa$le :/ data for c&ildren are $ased on studies 'ostly fro' resource-ric& countries"
D

9or c&ildren five years and older, it is reco''ended t&at t&res&olds used for adults to initiate ART are used to si'plify progra''e approac&es" Ta$le 3 su''ari,es t&e reco''endations for initiating ART in HIV-infected infants and c&ildren ac-cording to t&e clinical stage and t&e availa$ility of i''unological 'ar4ers #revised in 1C1C%"

Ta$le 3. Reco''endations for initiating ART in infants and c&ildren; revised in 1C1C
Age Infants and c&ildren J1 'ont&s of age +:/ M A$solute :/ All All
c c a,$

P1 'ont&s of age to 5* 'ont&s of age L15 D L55C cellsB''

9ive years of age or older 0A D LD5C cellsB'' #As in adults%

1 2 3

All HIV-infected infants s&ould receive ART due to t&e rapid rate of disease progression" :ountries wit& relia$le access to :/ 'onitoring 'ay c&oose to apply clinical and i''unological criteria for initiation of ART in c&ildren aged 11 6 1D 'ont&s" In c&ildren wit& a$solute ly'p&opaenia, t&e :/ percentage #+:/ M% 'ay $e falsely elevated"

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