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Critical issues in Children infected with HIV T. Puthanakit Chulalongkorn University, Bangkok, Thailand. Outline. Key issues in 2013 guidelines When to start ART What to start as a first-line ART regimen Treatment monitoring Second-line ART regimen. Key issues for Treatment and Care.

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Outline

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  1. Critical issues in Children infected with HIVT. PuthanakitChulalongkorn University,Bangkok, Thailand

  2. Outline • Key issues in 2013 guidelines • When to start ART • What to start as a first-line ART regimen • Treatment monitoring • Second-line ART regimen

  3. Key issues for Treatment and Care Programmatic Challenges • EID coverage remains poor • ART coverage only 34% (in 22 priority countries) • Limited availability of pediatric formulations and difficulties in harmonizing regimens with adults • Poor retention of children on ART and in care Technical Challenges • Provide the most effective regimen to deal with high VL and rapid disease progression • Optimization of ART treatment sequencing

  4. When to start ART

  5. What’s the evidence? Death 4% vs 16% • CHER trial(young infant) Early ART reduces mortality and HIV progression by75% • PREDICT trial(1-12 years) AIDS-free survival did not differ between deferred and early treatment group (median age 6.4 years). • IeDea SA: (2-5 years) Modelling of observational data showed no difference in mortality between early and starting ART based on current CD4 threshold. However,75% of children with CD4 > 25% (or 750 cells/mm3) become eligible by 3 years from enrolment. AIDS 6.3 % vs 25.6% 1 Violari A. NEJM 2008;359:2233-44. 2 Puthanakit T. Lancet Infect Dis 2012:933-941. 3 Schomaker M. IeDEA Southern Africa Collaboration 2012

  6. Move towards early ART • Suggestions that Early ART: • Improve immunological response • Reduce barrier to ART initiation • Improve retention in care • Settings where access to immunological testing is limited, the burden of paediatric HIV disease is high and paediatric ART coverage still low are the most likely to benefit • PLWA, caretakers and health care providers of HIV-infected children think that earlier initiation is preferable to facilitate family-based care, prevent loss to follow up and improve adherence. • Expanding ART to all children < 5 years will likely represent a small increased burden on current systems

  7. What ART to start: age < 3 years • When HIV RNA monitoring is available, consider to substitute LPV/r with NNRTI after virological suppression is sustained (conditional, low quality)

  8. What to ART start: age < 3 years • P1060 trial demonstrated that LPV/r is superior to NVP irrespective of NNRTI exposure (Palumbo 2010, Violari 2012) • Emerging evidence of high prevalence of NNRTI resistance irrespective of PMTCT exposure history (Kuhn et al. CROI 2013, Apollo et al. IAS 2013) • Low failure rate and good resistance profile at treatment failure with limited selection of resistance to NRTIs (Violari et al. Glasgow 2012) • Reduction of malaria incidence by 41% (Achan et al 2012)

  9. LPV/r vs NVP: Virological failure or death Achan J. N Engl J Med 2012;367:2110-8; Palumbo P. N Eng J Med 2010; 363:1510-20; Violari A. N Engl J Med 012;366:2380-9.

  10. Challenges of using LPV/r • Cold chain requirements • Low adherence due to poor palatability • Lack of FDC available • Lack of second line options in RLS • Interaction with TB drugs • Sprinkles soon available and “4in1”FDC are under development • Simplification by switching to NVP once virological suppression is achieved is safe in children without baseline resistance to NNRTI (Coovadia et al 2010) • 3NRTI regimen to be considered as an option for the duration of TB co-treatment (Arrow trial 2013)

  11. What to start in > 3 years

  12. What to start in > 3 years • Opportunity for harmonization with adults – improve children’s access to ART • Convenienceof once daily regimens and FDC where available (EFV preferred) • Better sequencing of therapy: non-thymidine analogues (ABC and TDF) as 1st line followed by AZT as 2ndline. Implementation Considerations • Experience with TDF in children is limited and long term impact is unknown • Feasibility highly dependent on the toxicity monitoring required • TDF-containing FDCs needs to be made available

  13. Rationale: Viral load Monitoring Targeted viral load monitoring (suspected clinical or immunological failure) Routine viral load monitoring (early detection of virological failure) • To provide an early and more accurate indication of treatment failure, reducing the accumulation of HIVDR mutations and improving clinical outcomes. • Can also help to discriminate between treatment failure and non-adherence • Can serve as a proxy for the risk of transmission at the population level Test viral load Viral load >1000 copies/ml Evaluate for adherence concerns • Harmonized monitoring approaches between adults and children • Lack of viral load or CD4 capacity should not prevent starting ART • If VL availability limited, phase in use of targeted approach (or CD4 / clinical monitoring) Repeat viral load testing after 3–6 months Viral load ≤1000 copies/ml Viral load >1000 copies/ml Maintain first-line therapy Switch to second-line therapy

  14. Second line ART • Failure of a first-line NNRTI-based regimen a boosted PI plus two NRTIs (LPV/r is the preferred boosted PI) (Strong recommendation, moderate-quality evidence) • Failure of a first-line LPV/r-based regimen in children < 3 years old Remain on the same regimen plus improve adherence (Conditional recommendation, very-low-quality evidence) • Failure of a first-line LPV/r-based regimen in children > 3 years NNRTI plus two NRTIs; EFV is the preferred NNRTI (Conditional recommendation, low-quality evidence) • NRTIs backbone substitution after treatment failure ABC or TDF + 3TC (or FTC) AZT + 3TC AZT or d4T + 3TC (or FTC) TDF + FTC or ABC + 3TC (Strong recommendation, low-quality evidence)

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