1. What’s New in the Pediatric Guidelines? November 2012 Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children François-Xavier Bagnoud Center, School of Nursing, UMDNJ The Health Resources and Services Administration The National Institutes of Health

2. About This Presentation These slides were developed using the Pediatric Antiretroviral Guidelines updated in November 2012. The intended audience is clinicians involved in the care of patients with HIV infection. For the complete text of the guidelines, please visit: www.aidsinfo.nih.gov. Because the field of HIV care is changing rapidly, users are cautioned that the information in this presentation may become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. – AETC NRC http://www.aidsetc.org November 2012 2 www.aidsetc.org 2

3. Identification of Perinatal HIV Exposure  When maternal HIV test results are unavailable or their accuracy cannot be evaluated, infant HIV antibody testing is indicated to identify HIV exposure.  If positive, further testing is needed to diagnose HIV infection. November 2012 3 www.aidsetc.org

4. Identification of Perinatal HIV Exposure (2)  The risk of transmission is increased in infants born to women with suspected acute HIV during pregnancy or lactation  Maternal testing should include HIV RNA and antibody testing  Breast-feeding should stop until HIV infection is excluded  Guidelines for care of women and their infants with acute or early HIV: http://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf November 2012 4 www.aidsetc.org

5. Infant HIV Diagnosis: Non-Subtype B  For infants with suspected exposure to non- subtype B, consider initial testing with an assay that is sensitive for non-subtype B virus  If non-subtype B exposure is suspected in infants with negative DNA PCR:  Repeat testing with one of the newer RNA assays  Consult an expert  Monitor closely and conduct HIV serologic testing at 18 months November 2012 5 www.aidsetc.org

6. Infant HIV Diagnosis: HIV-2 Infection Infants born to HIV-2-infected mothers:  Use antibody test that detects HIV-2  Most tests detect both HIV-1 and HIV-2 but do not distinguish between them; can use Multispot or (if HIV- 2 suspected) HIV-2-specific test  Use HIV-2-specific virologic assays at time points similar to those used for HIV-1 testing  HIV-2 assays are not commercially available; National Perinatal HIV Hotline (1-888-448-8765) can advise on sites that perform this testing November 2012 6 www.aidsetc.org

7. Diagnostic Testing in Children with Non-Perinatal HIV Exposure  Recommendations for infants who are breast- fed by an HIV-infected woman:  Immediate virologic testing  Discontinue breast-feeding  Follow-up virologic testing at 4-6 weeks and at 3 and 6 months after breast-feeding cessation if initial test results are negative November 2012 7 www.aidsetc.org

8. Diagnostic Testing in Children with Non-Perinatal HIV Exposure (2)  Other potential sources of HIV exposure:  Sexual abuse  Parenteral exposure via contaminated blood products (eg, some international adoptions)  Receipt of premasticated or prechewed food from an HIV-infected caregiver  Accidental needle sticks  Behavioral risks November 2012 8 www.aidsetc.org

9. When to Start ART in ARV-Naive Children  CD4 count and CD4 thresholds are now offered for children >12 months of age; in the case of discordance between CD4 and CD4 percentage, decisions should be based on the lower value  Recent analyses show that CD4 counts provide greater prognostic value than CD4 percentage  CD4 thresholds for treatment have been subdivided into age groups: 1 to <3 years, 3 to <5 years, and ≥5 years November 2012 9 www.aidsetc.org

10. When to Start ART in ARV-Naive Children (2) November 2012 10 www.aidsetc.org AgeCriteriaRecommendation <12 months Regardless of clinical symptoms, immune status, or HIV viral load Treat (AI for 12 weeks to <12 months) 1 to <3 years AIDS or significant HIV-related symptoms b CD4 cell count <1000 cells/µL or CD4 percentage <25% Asymptomatic or mild symptoms c and CD4 cell count >1000 cells/µL or CD4% ≥25% Treat (AI*) Treat (AII) Consider treatment d (BIII) b CDC Clinical Categories C and B (except single episode of serious bacterial infection) c CDC Clinical Category A or N or single episode of serious bacterial infection d If VL is >100,000 copies/mL, evidence for initiation of ART is stronger. (BII)

11. When to Start ART in ARV-Naive Children (3) AgeCriteriaRecommendation 3 to 5 years AIDS or significant HIV-related symptoms b CD4 <750 cells/µL or percentage <25% c Asymptomatic or mild symptoms c and CD4 ≥750 cells/µL or percentage ≥25% Treat (AI*) Treat (AII) Consider ART (BIII) ≥5 yearsAIDS or significant HIV-related symptoms b CD4 ≤500 cells/µL Asymptomatic or mild symptoms c and CD4 >500 cells/µL Treat (AI*) Treat (AI* for CD4 <350 and BII* for CD4 350-500) Consider ART (BIII) November 2012 11 www.aidsetc.org b CDC Clinical Categories C and B (except single episode of serious bacterial infection) c CDC Clinical Category A or N or single episode of serious bacterial infection d If VL is >100,000 copies/mL, evidence for initiation of ART is stronger. (BII)

12. When to Start ART in ARV-Naive Children (4) November 2012 12 www.aidsetc.org  Children in whom ART is deferred need close follow- up; factors to consider in deciding when to initiate ART in children in whom ART was deferred include: Increasing VL (such as VL approaching 100,000 copies/mL) CD4 count or percentage approaching age-related threshold for ART Development of clinical symptoms Ability of caregiver and child to adhere to regimen

13. When to Start ART in ARV-Naive Children (5)  In children with lower-strength (B level) recommendations for treatment, VL >100,000 copies/mL provides stronger evidence for initiation of ART (BII)  Assess issues associated with adherence before initiation of therapy (AIII)  Parents/caregivers or providers may elect to defer therapy based on clinical or psychosocial factors November 2012 13 www.aidsetc.org

14. Initial Combination Therapy for ART-Naive Children: New Recommendations  Tenofovir (TDF) use: based on Tanner staging  NRTI combination of TDF + 3TC or FTC:  Recommended for adolescents Tanner 4 or 5 (AI*)  Alternative for adolescents Tanner 3  Use in special circumstances for children ≥2 years of age and Tanner 1 or 2 November 2012 14 www.aidsetc.org

15. Initial Combination Therapy for ART-Naive Children: New Recommendations (2)  Etravirine and rilpivirine: Not Recommended as initial therapy because of lack of experience and dosing information for children  Boosted fosamprenavir + 2 NRTIs: Alternative option in children >6 months  Darunavir/ritonavir + 2 NRTIs: Alternative in children ≥3 years; once-daily dosing not recommended in children <12 years November 2012 15 www.aidsetc.org

16. Initial Combination Therapy for ART-Naive Children: New Recommendations (3)  Raltegravir: FDA approved for children ≥2 years; Not Recommended for initial therapy: insufficient data  Elvitegravir: Not approved for children; Not Recommended: insufficient data for use in children  Efavirenz: Until additional safety information is available, strongly consider avoiding efavirenz in adolescent females not using effective or consistent contraception November 2012 16 www.aidsetc.org

17. Initial Combination Therapy for ART- Naive Children: Preferred Regimens* AgePreferred Regimens ≥14 days to <3 years2 NRTIs + LPV/r a ≥3 years2 NRTIs + EFV b 2 NRTIs + LPV/r ≥6 years2 NRTIs + ATV + low-dose RTV 2 NRTIs + EFV b 2 NRTIs + LPV/r a LPV/r should not be given to neonates before a postmenstrual age of 42 weeks and postnatal age of at least 14 days b Use EFV only in children >3 years and weight >10 kg; not recommended for adolescent females who may become pregnant November 2012 17 www.aidsetc.org *No change from previous guidelines

18. Initial Combination Therapy for ART- Naive Children: Alternative Regimens AgeAlternative regimen Any age2 NRTIs + NVP c ≥3 years2 NRTIs + DRV + low-dose RTV >6 months (new)2 NRTIs + FPV d + low-dose RTV d FPV with low-dose RTV should only be given to infants born at ≥38 weeks who have attained a postnatal age of 28 days and to infants born before 38 weeks who have reached a postmenstrual age of 42 weeks c NVP should not be started in postpubertal girls with CD4 count of >250 cells/µL unless expected benefits clearly outweigh risks November 2012 18 www.aidsetc.org

19. Initial Combination Therapy for ART- Naive Children: Regimens for Use in Special Circumstances* November 2012 19 www.aidsetc.org Regimens for Use in Special Circumstances 2 NRTIs + unboosted ATV (for treatment-naïve adolescents ≥13 years and weight >39 kg) 2 NRTIs + unboosted FPV (children ≥2 years) 2 NRTIs + NFV (children ≥2 years) ZDV + 3TC + ABC *No change from previous guidelines

20. Initial Combination Therapy for ART-Naive Children: 2-NRTI Backbone Options PreferredABC + (3TC or FTC) (children ≥3 months) TDF + (3TC or FTC) (adolescents Tanner 4 or 5) (new) ZDV + (3TC or FTC) AlternativeddI + (3TC or FTC) TDF + (3TC or FTC) (adolescents Tanner 3) (new) ZDV + ABC ZDV + ddI Use in Special Circumstances d4T + (3TC or FTC) TDF + (3TC or FTC) (prepubertal children aged >2 years and adolescents Tanner 1 or 2) (new) November 2012 20 www.aidsetc.org

21. Treatment Failure  Management of treatment failure has been more clearly limited to management of virologic failure  There is no consensus on how to manage immunologic or clinical failure in the absence of virologic failure November 2012 21 www.aidsetc.org

22. Treatment Failure (2)  Virologic suppression: VL below the level of quantification using the most sensitive assay (<20-75 copies/mL)  Older assays with lower limits of 200 or 400 copies/mL are acceptable if they are the only option; levels reported as detectable but below the level of quantification should not be considered as evidence of virologic failure November 2012 22 www.aidsetc.org

23. Treatment Failure (3)  Viral rebound: VL above the level of quantification after a child achieved virologic suppression on ART  Isolated “blips” above the level of quantification but <1000 copies/mL are common and generally do not indicate failure  Children with higher VL at initiation of therapy (especially infants) may take longer to reach undetectable levels November 2012 23 www.aidsetc.org

24. Adolescent-Specific Issues  Discuss reproductive plans, including preconception care, contraception and safer sex regularly  Continue to be aware of potential interactions between ART and hormonal contraceptives  Some newer agents (eg, raltegravir) appear to have no interactions  There may be differences in pregnancy-related morbidities among perinatally infected adolescents (as compared with adult cohorts) November 2012 24 www.aidsetc.org

25. Adolescent-Specific Issues (2)  Outcomes are variable in young adult patients transitioned to adult care  Factors to consider during transition include social determinants, such as:  Developmental status  Behavior/mental health issues  Housing  Family support  Employment  Recent discharge from foster care or prison  Peer pressure  Illicit drug use November 2012 25 www.aidsetc.org