PresentaciÃ3n en PowerPoint de Petros Isaakidis.


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  • MSF: Medecins SansFrontieres NCHADS: Cambodian National Program for Control of HIV/AIDS, Dermatology and STDs AHC: Angkor Hospital for Children
  • MSF: Medecins SansFrontieres NCHADS: Cambodian National Program for Control of HIV/AIDS, Dermatology and STDs AHC: Angkor Hospital for Children
  • NECHR: National Ethics Committee for Health Research, Cambodia MSF ERB: Medecins Sans Frontieres Ethics Review Board IRB of HAC: Institutional Review Board of Angkor Hospital for Children
  • Large patient surveys in industrialized countries: 24%-36% of patients with HbA1c < 7% 20% -30% of patients in Thailand and 46% in Brazil with HbA1c < 7% In three Caribbean countries, 50% of patients had poor blood glucose control (>=10mmol/l random) In a diabetic program in Eritrea the median HbA1c was 8.5% after treatment 64% patients had poor control of HbA1C (>10%) over a one-year period in Papua New Guinea
  • PresentaciÃ3n en PowerPoint de Petros Isaakidis.

    1. 1. High survival and treatment success sustained after 2 and 3 years of ART for children in Cambodia Petros Isaakidis , Marie-Eve Raguenaud, Vantha Te, Chhraing Seng Tray, Kazumi Akao, Varun Kumar, Sopheak Ngin, Eric Nerrienet, Rony Zachariah
    2. 2. <ul><li>Medium and long-term outcomes of antiretroviral therapy (ART) in children remain poorly documented in resource-limited settings </li></ul><ul><li>Even less evidence is out there on virological outcomes and antiretroviral drug resistance amongst children </li></ul>Background 1/2
    3. 3. <ul><ul><li>Médecins Sans Frontières (MSF) </li></ul></ul><ul><ul><li>the National Centre for HIV/AIDS, Dermatology and STIs (NCHADS) </li></ul></ul><ul><ul><li>Angkor Hospital for Children (AHC ) </li></ul></ul><ul><li>have been treating HIV+ children in 2 clinics in Siem Reap and Takeo provinces since 2003 </li></ul>Background 2/2
    4. 4. Methods 1/1 <ul><li>Cross-sectional survey with viral load and genotyping </li></ul><ul><li>All children ( ≤15 years) treated with 1 st -line </li></ul><ul><li>ART for at least 24 months were eligible for inclusion </li></ul><ul><li>Survival, CD4-evolution, virological response and risk factors for failure were assessed </li></ul>
    5. 5. Results 1/9 All children started ART N=670 Children assessed N=268 All children N=1168 Children with at least 24M of ART N=285 6 transferred-out 2 declined 9 no sample
    6. 6. Results 2/9 overall survival <ul><li>1168 HIV+ children registered </li></ul><ul><li>670 (57%) started ART from 01/2003 to 12/2007 </li></ul><ul><li>Survival probability was 0.93 (95% CI: 0.91-0.95) and 0.91 (95% CI: 0.88-0.93) at 24 and 36 months respectively </li></ul>
    7. 7. Results 3/9 overall survival at M24 & M36 0.93 0.91
    8. 8. Results 4/9 children characteristics <ul><li>Among 268 children assessed </li></ul><ul><ul><li>130 completed 24 months </li></ul></ul><ul><ul><li>138 completed 36 months of ART </li></ul></ul><ul><li>Median follow-up time since ART initiation 36.2 months (IQR: 30.7-40.7) </li></ul><ul><li>128 (48%) female </li></ul><ul><li>Median age: 6ys (IQR: 4-8) </li></ul>
    9. 9. Results 5/9 immunological recovery <ul><li>Median CD4 gain for children >5 years </li></ul><ul><ul><li>+704 cells/ml at 24 months </li></ul></ul><ul><ul><li>+737 cells/ml at 36 months </li></ul></ul><ul><li>Median CD4% gain for children <=5 years </li></ul><ul><ul><li>+15.2% at 24 months </li></ul></ul><ul><ul><li>+15.0% at 36 months </li></ul></ul>
    10. 10. Results 6/9 CD4 gain, children >5 years
    11. 11. Results 7/9 CD4% gain, Children =<5 years
    12. 12. Results 8/9 virological success & ARV mutations <ul><li>112/130 (86.1%) after 24 months </li></ul><ul><li>134/138 (97.1%) after 36 months </li></ul><ul><li>had undetectable viral load (<250 copies/ml) </li></ul><ul><li>22 children had VL>1,000 copies/ml and 21/21 presented mutations conferring resistance mostly to lamivudine and NNRTIs </li></ul>
    13. 13. Results 9/9 multivariate analysis <ul><li>Risk factors for failure after 24 and 36 months were CD4-counts below WHO threshold for severe immunosupression at month 24 and 36 respectively </li></ul><ul><ul><li>(adjusted HR: 18.7 (4.0-87.5), P <0.001) </li></ul></ul><ul><li>Orphan status did not predict failure </li></ul>
    14. 14. Discussion 1/5 <ul><li>93% of children in our HIV-programs were alive and in care </li></ul><ul><li>Rapid and sustained immune restoration and a high virological success rate of >86% for children on ART >24 months in a programmatic setting </li></ul>
    15. 15. <ul><li>6/22 patients developed a profile of extensive resistance, limiting the options for effective 2nd line ART regimens </li></ul><ul><li>An expanded drug formulary is needed </li></ul><ul><li>Drugs used for standardized 2nd line regimens, (e.g. abacavir, didanosine and lopinavir /ritonavir) are still discouragingly expensive </li></ul>Discussion 2/5
    16. 16. <ul><li>WHO immunological criteria for failure: </li></ul><ul><ul><li>Specificity: 100% </li></ul></ul><ul><ul><li>Positive Predictive Value : 100% </li></ul></ul><ul><ul><li>Negative Predictive Value: 92.5% </li></ul></ul><ul><ul><li>Sensitivity: 10% </li></ul></ul><ul><li>Relying exclusively on WHO criteria would have led to a misclassification of 20 out of 22 failures </li></ul><ul><li>Viral load measurement should be routine monitoring tool for ART in children </li></ul>Discussion 3/5
    17. 17. <ul><li>At 12 months being orphan was found to be a greater risk for virological failure (early predictor?) </li></ul><ul><li>Greater attention was given to adherence support for these children & their caregivers </li></ul><ul><ul><li>intensive home-based care </li></ul></ul><ul><ul><li>specific counseling sessions </li></ul></ul><ul><ul><li>social support by a social worker </li></ul></ul><ul><ul><li>training sessions to staff in orphanages </li></ul></ul>Discussion 4/5
    18. 18. <ul><li>Programmatic, no research setting </li></ul><ul><li>Very few infants started on ART, especially in the early years (no PCR) </li></ul><ul><li>Previous ART experience only self-reported </li></ul><ul><li>No systematic record of antiretroviral drug toxicities </li></ul>Discussion 5/5 Study limitations
    19. 19. Conclusions <ul><li>Good survival rate, immunological restoration and viral suppression can be achieved and sustained after 2 to 3 years of ART among children in resource-constrained settings </li></ul><ul><li>Increased access to routine virological measurements is needed to allow for timely and accurate diagnosis of treatment failure </li></ul>
    20. 20. Thank you
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