WHO technical recommendations on pediatric HIV care

Summary of revised recommendations on diagnosis, clinical staging & immunological classification, & ART

Dr Siobhan CROWLEY WHO, Geneva

HIV Department

Universal Access to comprehensive package of prevention & care

CARE TREATMENT AND SUPPORT FOR ALL HIV EXPOSED Early diagnostic testing for HIV infection Infant feeding counselling and support Co-trimoxazole prophylaxis Assessment, management and follow up of common conditions Regular Growth monitoring, developmental assessment and support Immunization Prevention, screening and management of tuberculosis Prevention and treatment of malaria

Care and support for for uninfected

Care and support where status still

unconfirmed

Care for the infected child

Early Diagnosis

Public health programming for HIV Care

Multiple entry & delivery points PMTCT Hospital/U5Clinic/NRU - symptomatic patients Community facilities Home based care and outreach Linkages with preventive services inc HIV T&C

Family friendly care children + primary care givers seen in same setting testing, support for siblings

Chronic disease approach Clinical care teams

Integrated care & decentralized delivery links to facilities closer to community (HBC) + task shifting

Life course approach Infants (< 18 mo)

Problem with confirming HIV diagnosis Rapid progression Less easy to use ARV formulations

Children (18 mo – 10 yr) Survivors Toxicities Long-term non-progressors Informing and disclosing

Adolescents (> 10 yr) Identity and self image Adherence Toxicities Informing & disclosure to family, peers and partners Sexuality and fertility

Co-trimoxazole • New Guidelines –

– Experts meeting May 2005– Guidelines development group review April 2006– Due for publication June 2006

They address: • Adults and children • Starting, discontinuation• Toxicity and dosing

Co-trimoxazole – when to start Situation

Confirmed HIV infected infants and children2 HIV exposed infants and children1 under 1

year 1-4 years 5 years and older

Universally indicated, from 4-6 weeks until risk of HIV transmission ceased [A-III]

All regardless of % CD4+ or clinical status.3 [A-II]

WHO stages 2, 3 and 4 regardless of % CD4 + OR Any WHO stage and %CD4+ < 25 [A-I]

Any WHO clinical

stage and CD4< 3502

[A-III]

OR WHO stage 3 or 4 irrespective CD4 [A-I]

Universal option: Prophylaxis for all infants and children born to HIV infected mothers; may be considered in settings with high prevalence of HIV and limited health infrastructure. [C-IV]

Discontinuation of primary CTX prophylaxis

HIV-exposed infants & children confirmed HIV uninfected

HIV infected & ART - related immune recovery

CTX d/c when HIV infection has been definitely excluded [A-I]

CTX continued indefinitely

[A-IV]

However if : Child > 5 yrs started CTP during infancy, d/c CTP can be considered where: stable on ART > 12 mo + CD4 > used to initiate CTX prophylaxis + good adherence + secure supply + access to ART [C- IV] & restart if CD4 falls below the initiation threshold or if new or recurrent WHO 2, 3 or 4 conditions occur [A- IV]

Discontinuation in the context of CTX adverse reactions

Severe adverse reactions to CTX in children uncommon:

(in the CHAP study, one child developed rash among 534 children randomized to CTX or placebo)

– CPT prophylaxis may need to be d/c in event of an adverse drug reaction.

– Insufficient data on CPT desensitization in children to make any recommendations on its use in resource limited settings.

– All starting CPT, & their guardians and caregivers, need verbal or written information on potential adverse effects and advised to stop the drug and report to their nearest health facility if CTX-related adverse events are suspected.

Discontinuation of secondary CTX prophylaxis

Two options can be recommended:

– Secondary prophylaxis should be administered lifelong. [B-III]

– Discontinuation of secondary CTX prophylaxis may be considered in children with immune recovery on ART based on the same CD4 criteria as for discontinuing primary prophylaxis. [C-III]

(based on evidence that secondary CTX prophylaxis can be safely stopped in adults based CD4 cell count guided immune recover on ART)

HIV Care & ART for children: guidelines development process

Diagnosis of HIV Working Draft prepared from TRG Experts review - April 2006 Draft for public review – end June 2006

Assessment & classification of HIV June 2004 – expert meet Regional consultations Dec 2005-Oct 2005 Global consensus meeting – April 2006 Now Final editing and layout – publication imminent

ART June 2005 -TRG expert meeting Public review Oct- Nov 2005 Writing group review Nov 2005 Now Final editing and layout – publication imminent

Method of diagnosis Recommendations for use Strength of recommendation/ level of evidence

Virological methods

To diagnose infection in infants aged under 18 months; initial testing is recommended from 6 weeks of age

HIV DNA [A(I)] HIV RNA [A(I)] U p24 ag [CII]

To diagnose HIV infection in mother or identify HIV exposure of infant

A(I)

To diagnose HIV infection in children aged 18 months or more

A(I)

To identify HIV-positive children aged under 18 months and support a presumptive clinical diagnosis of severe HIV disease to allow initiation of ART

A(IV) a

To exclude HIV infection where negative in < 18 month old HIV exposed non breastfed infant

A(I)

HIV antibody testing

To exclude HIV infection where negative and HIV exposed infant discontinued breastfeeding for > 6 weeks

A (IV)

RECOMMENDATIONS - LABORATORY METHODS FOR EARLY DIAGNOSIS OF HIV INFECTION

1. Countries should strive to ensure access to virological testing (VT) for HIV is made available national wide [ A (I)]

2. Currently available HIV VT that can be considered include:– HIV PCR DNA [A(I)]– HIV RNA [A(I)]– U p24 [B (III)]

Commercially available and in-house methods can be used provided their quality is validated, assured and documented.

4. Dried blood spots (DBS) can facilitate decentralization of access to HIV VT. Currently procedures for use of DBS exist for the following VT assays:

– HIV DNA [A (I)]– HIV RNA [A (II)]– HIV UP24 [C (IV)]

More evidence to support these recommendations should become available and published shortly.

RECOMMENDATIONS - VIRAL TESTING contd

• All the above HIV viral tests can be considered for use from 6 week of age irrespective of maternal ARV prophylaxis or ART DNA/RNA A(I)

• Time period for use of viral tests to provide reliable diagnosis after discontinuation of Breastfeeding is 6 weeks A (II)

• Single positive virological test at any age, should trigger clinical management as if HIV infected A (I)

Presumptive diagnosis of severe HIV in HIV exposed infant

Seropositive Infant; • AIDS indicators condition • Symptomatic with 2 or > two or more of the following:

– oral thrush;– severe pneumonia**– severe sepsis*

• Other factors to support diagnosis of severe HIV include:

– Recent HIV-related maternal death; or – Advanced HIV disease in the mother; or– No history of PMTCT intervention– CD4 <25%

• Confirmation of the diagnosis of HIV infection should be sought as soon as possible.(*) As defined in IMCI

Revised Staging & Classification

Clinical classification

Stage 1 Stage 2 Stage 3 Stage 4

No symptoms

Mild Advanced Severe

Immunological classificationNot significant

Mild Advanced Severe

+

Clinical classification on treatment

T1 T2 T3 T4

Immunological classification- all ages

HIV associated immunodeficiency

Age related CD4

(%CD4+ or absolute count)

<11m (%)

12-35m (%)

36-59m

(%)

>5yr

(count/%)

Not significant > 35 >30 >25 <500

Mild 30-35 25-30 20-25 350-499

Advanced 25-29 20-24 15-19 201-349

Severe <25 <20 <15 <200

Mortality by WHO stage (from CHAP data courtesy of Di Gibb)

0.00

0.25

0.50

0.75

1.00

0 .5 1 1.5 2 2.5

Years from randomisation

STAGE 2

STAGE 3

STAGE 4

Pro

port

ion

su

rviv

ing

Similar separation in all age groups, although absolute mortality varies

0

5

10

15

20

25

30

0 1 2 3 4 5 6 7 8 9 10

Age (years)

Pro

babi

lity

of d

eath

(%)

CD4%<25 (<1yr), <20% (1 to <3 yrs), <15% (3 to <5 yrs), <15% (≥ 5 yrs)

CD4<1500 (<1yr), <750 (1 to <3 yrs), <350 (3 to <5 yrs), <200 (≥ 5 yrs)

TLC<4000 (<1yr), <3000 (1 to <3 yrs), <2500 (3 to <5 yrs), <2000 (≥ 5 yrs)

12-month mortality risk at selected thresholds for CD4%, CD4 count and TLC, by age

CD4 Criteria for severe immunodeficiency

Immunology

marker

Age specific recommendation to initiate ART [A-I]< 11 mo 12-35 mo 36-59 mo > 5 yrs

% CD4 + <25 < 20 <15 <15CD4 count/cells mm3

<1500 <750 <350 <200

TLC criteria of severe HIV immunodeficiency

Age-specific recommendation to initiate ARTb Immunological

marker

≤11 mo 12 mo-

35 mo

36 mo-

59 mo

5 - 8 years

TLC

≤4000

cells/mm3

≤3000

cells/mm3

≤2500

cells/mm3

≤2000

cells/mm3

(c)

(for use only in infants children with confirmed HIV infection, clinical stage 2 & CD4 measurement is not available)

Recommendations for initiating ART in HIV infected infants

WHO stage

Availability CD4

Age specific treatment recommendation

[ A II ]

<11 months > 12 months

1 CD4 CD4 guided

No CD4 Do not treat

2 CD4 CD4 guided

No CD4 TLC guided

3 CD4 Treat all Treat all; can delay start of ART if CD4 above threshold and child has TB, HOL, LIP

No CD4 Treat all

4 CD4 Treat all

No CD4

ABC

AZT* or d4T

NVP

EFV

3TC or FTC

Triple NRTI alternative approach#

# Triple NRTI regimen can be considered where NNRTI options are complicated (e.g. viral hepatitis co-infection, TB co infection, pregnant adolescents or if CD4 count > 250 cells /mm3; severe reactions to NVP or EFV and HIV-2 infection).

First Line ARV Drugs in children and young adolescents

ZDV or d4T* NVP or EFV3TC or FTC

Triple NRTI alternative

ddI + ABC + PI/r

+ +

ZDV or d4T* ABC3TC or FTC+ + NVP or EFV + PI/r

Preferred first-line Second-line*

ABC

NVP or EFV3TC or FTC+ + ddI + ZDV + PI/r

* 3TC can be maintained in a second line regimen

Clinical staging events to guide decision-making on ART switching New or recurrent

event on ART a Recommendations Additional management options

Asymptomatic(T1)

Do not switch regimen

• Maintain scheduled follow up visits including CD4 monitoring (if available)

• Continue to offer adherence support

Stage 2 event(T2 )

Do not switch regimen b

• Treat and manage staging event• Assess and offer adherence support • Check if on treatment at least 6 months • Assess continuation or reintroduction of OI prophylaxis • Schedule earlier visit for clinical review and consider CD4 (if

available) c

Stage 3 event(T3)

Consider switchingregimen b d

• Treat and manage staging event and monitor response• Assess and offer adherence support• Check if on treatment at least 6 months • Check CD4 cell count (if available) c d

• Assess continuation or reintroduction of OI prophylaxis• Institute more frequent follow up

Stage 4 event(T4)

Switch regimen b e

• Treat and manage staging event and monitor response• Assess and offer adherence support • Check if on treatment at least 6 months • Assess continuation or reintroduction of OI prophylaxis• Check CD4 cell count (if available) c

a. Clinical stages refer to the clinical stage while on ART for at least 6 months (termed T1, T2, T3, T4)a. Differentiation of opportunistic infections from immune reconstitution syndrome is necessary.b. Treat and manage the staging event before measuring CD4 cell count.c. Certain WHO clinical Stage 3 conditions (e.g. pulmonary TB, severe bacterial infections), may not be an indication of treatment failure,

and thus not require consideration of second-line therapy; response to appropriate therapy should be used to evaluate the need for switching of therapy.

d. Some stage 4 conditions (uncomplicated TB pleural disease, esophageal candidiasis, recurrent bacterial pneumonia) may not be an indicator of treatment failure and thus not require consideration of second-line therapy; response to appropriate therapy should be used to evaluate the need to switch therapy.

Simplified weight based dosing tables

Further information crowleys@who.int

Web page: http://www.who.int/hiv/paediatric/en/index.html

Scaling up antiretroviral therapy in resource-limited settings: Treatment guidelines for a public health approach' are available at: http://www.who.int/3by5/publications/documents/arv_guidelines/en/

ARV Toolkit & HIV Testing & counselling toolkit on line All integrated management tools:http://who.arvkit.net/tc/files/chronic_care_3_may_06.pdf

Resources on HIV testing in children: http://www.who.int/hiv/toolkit/arv/en/index.jsphttp://www.who.arvkit.net/tc/en/content.jsp?d=tc.10.23