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Cissy Kityo MD SATuRN-PASER Workshop November 21-22, 2013

Monitoring Antiretroviral Resistance in Children (MARCH). Cissy Kityo MD SATuRN-PASER Workshop November 21-22, 2013. HIVDR: Predisposing factors in children. Exposure to antiretroviral medication for PMTCT Extended Nevirapine/Zidovudine Single dose nevirapine

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Cissy Kityo MD SATuRN-PASER Workshop November 21-22, 2013

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  1. Monitoring Antiretroviral Resistance in Children (MARCH) Cissy Kityo MD SATuRN-PASER Workshop November 21-22, 2013

  2. HIVDR: Predisposing factors in children • Exposure to antiretroviral medication for PMTCT • Extended Nevirapine/Zidovudine • Single dose nevirapine • Higher baseline viral loads, longer time to suppression • Inappropriate dosing because of limited paediatric formulations and weight changes • Limited training of HCW in pediatric management • Adherence issues • Reliance on adult caretakers • Poorly palatable formulations (esp. liquids)

  3. MARCH - objectives • Measure baseline HIVDR prevalence in children initiating first- or second-line ART • Monitor virological response to treatment • Determine prevalence and patterns of HIVDR in children with detectable viral load • Identify risk factors for virologic failure and HIVDR

  4. Study design • Prospective, observational cohort study of HIV- positive children ≤ 12 years • Eligible when initiating first-line ART or switching to second-line ART due to treatment failure • Follow-up >2 years, VL testing every 6 months • HIVDR test if VL >1000 copies/ml

  5. Exclusion criteria • Re-initiation of first-line ART NB: previous use of ARV’s for prophylaxis (PMTCT or PEP) is allowed

  6. Study Flow

  7. Study samples • 6ml collected at baseline and every FU-visit • Barcoded lab kit; barcode entered on CRF • VL testing at reference laboratory, if VL > 1000 copies: HIVDR testing MARCH MARCH

  8. MARCH-Uganda study • Prospective cohort study of 360 children in Uganda on ART • Initiated in January 2010 • Funded by EDCTP, NACCAP

  9. MARCH-UG Progress overview up to October 2013

  10. MARCH-UG Progress up to October 2013

  11. MARCH-uganda: study flow

  12. MARCH-Uganda: first results

  13. Baseline characteristic of children initiating first-line ART Boender et al, AIDS research and treatment 2012

  14. HIVDR among children initiating first-line ART Frequencies (%) of HIVDR mutations in patients initiating first-line treatment either ARV-naïve or with previous PMTCT (n=14) or unknown exposure status (n=32) Unpublished

  15. Resistance patterns before first-line ART initiation Unpublished

  16. Factors associated with HIVDR before first-line ART initiation Unpublished

  17. MARCH-Uganda: Characteristics of children switching to 2nd-line ART • 50 children enrolled in MARCH at time of failure of NNRTI-based first-line ART: 29 in Kampala, 18 in Mbale, 3 in Fort Portal • Baseline characteristics: Sigaloff et al, AIDS research and human retroviruses 2013

  18. Resistance patterns at switch (n=44)

  19. MARCH-Uganda: Susceptibility to RT-inhibitors at time of switch Predicted HIV susceptibility to nucleoside and nonnucleoside reverse transcriptase inhibitors in children with first-line antiretroviral therapy failure (n = 44) Sigaloff et al, AIDS research and human retroviruses 2013

  20. Planned analyses • Outcome of children on first-line: ARV-naive versus exposed • Outcome of children on second-line after switch • Comparative study between Uganda and Nigeria?

  21. MARCH Uganda: sub-study results Research question: • What are the factors influencing the timing of pediatric ART initiation? Methods • Both quantitative and qualitative data analysis Boender et al, AIDS research and treatment 2012

  22. Risk factors for late disease stage at presentation • Lack of HIV-specific perinatal care • Child living without parents • Financial constraints of the caregiver • Caregivers’ unawareness of HIV symptoms • Stigma and fear Boender et al, AIDS research and treatment 2012

  23. Conclusions • Important barriers to care remain for children, accounting for< 35% ART coverage in most African regions • NNRTI resistance most common: K103N, Y181C • NRTI: M184V en TAMs • Besides PMTCT exposure, maternal ART use and breastfeeding may be important risk factors for baseline HIVDR  • Extensive resistance at switch (46% multiple TAMs) due to delayed switching  fear of exhausting treatment options in children?

  24. Conclusions • HIVDR is this cohort starting ART is classified as moderate by WHO calls for extensive surveys to identify risk factors • HIV drug resistance among children is underreported, surveillance data necessary to inform pediatric guidelines

  25. All participants and their parents/caregivers JCRC, Uganda Cissy Kityo Peter Mugyenyi Victor Musiime Elizabeth Khauda Study staff European Developing Countries Trial Partnership Acknowledgements PharmAccess, AIGHD, AMC Tobias Rinke de Wit Kim Sigaloff Sonia Boender Raph Hamers Pascale Ondoa Job Calis Sibyl Geelen Michael Boele van Hensbroek University Medical Center, Utrecht Rob Schuurman World Health Organization (WHO) Michael Jordan Sylvia Bertagnolio

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