1. 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

2. 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

3. 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

4. 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

5. 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

6. Co-trimoxazole – when to start

7. 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]

8. 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.

9. 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)

10. 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

12. 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. 3.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.

13. 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)

14. 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

15. Revised Staging & Classification Clinical classification Stage 1Stage 2Stage 3Stage 4 No symptoms MildAdvancedSevere Immunological classification Not significant MildAdvancedSevere + Clinical classification on treatment T1T2T3T4

16. 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 30-3525-3020-25350-499 Advanced 25-2920-2415-19201-349 Severe <25<20<15<200

17. Mortality by WHO stage (from CHAP data courtesy of Di Gibb) 0.00 0.25 0.50 0.75 1.00 0.511.522.5 Years from randomisation STAGE 2 STAGE 3 STAGE 4 Proportion surviving Similar separation in all age groups, although absolute mortality varies

18. 12-month mortality risk at selected thresholds for CD4%, CD4 count and TLC, by age

19. CD4 Criteria for severe immunodeficiency Immunology marker Age specific recommendation to initiate ART [A-I] < 11 mo12-35 mo36-59 mo> 5 yrs % CD4 + <25< 20<15 CD4 count/cells mm 3 <1500<750<350<200

20. TLC criteria of severe HIV immunodeficiency (for use only in infants children with confirmed HIV infection, clinical stage 2 & CD4 measurement is not available)

21. Recommendations for initiating ART in HIV infected infants WHO stage Availability CD4 Age specific treatment recommendation [ A II ] <11 months> 12 months 1CD4CD4 guided No CD4Do not treat 2CD4CD4 guided No CD4TLC guided 3CD4Treat allTreat all; can delay start of ART if CD4 above threshold and child has TB, HOL, LIP No CD4Treat all 4CD4Treat all No CD4

22. 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 /mm 3 ; severe reactions to NVP or EFV and HIV-2 infection). First Line ARV Drugs in children and young adolescents

23. 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* AB C NVP or EFV3TC or FTC ++ ddI + ZDV + PI/r * 3TC can be maintained in a second line regimen

24. Clinical staging events to guide decision-making on ART switching New or recurrent event on ART a RecommendationsAdditional management options Asymptomati c (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 switching regimen 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.

25. Simplified weight based dosing tables

26. 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/ 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.jsp http://www.who.arvkit.net/tc/en/content.jsp?d=tc.10.23