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Children and resistance to HIV: CHIPS data

Children and resistance to HIV: CHIPS data. Dr Katherine Boyd on behalf of C ollaborative HI V P aediatric S tudy ( CHIPS ) and the UK HIV Drug Resistance Database. Introduction. There are over 20 antiretroviral drugs to treat HIV infected children.

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Children and resistance to HIV: CHIPS data

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  1. Children and resistance to HIV: CHIPS data Dr Katherine Boyd on behalf of Collaborative HIV Paediatric Study (CHIPS) and the UK HIV Drug Resistance Database

  2. Introduction • There are over 20 antiretroviral drugs to treat HIV infected children. • A lack of age-appropriate formulations and pharmacokinetic data can result in sub-therapeutic concentrations. • Poor adherence can be a problem and cause resistance, particularly in adolescence. • Objectives: 1) Possible transmission of resistance. 2) Acquired resistance in children after starting ART.

  3. UK HIV Drug Resistance Database • Established in 2001 as a central repository of resistance tests carried out as part of routine care in the UK. • Contains all routinely-performed (or within PENTA trials) HIV drug resistance tests in the UK, 1998-2006, from all laboratories. • Data include some patient demographics, dates and locations of tests, and resistance mutations. • Drug susceptibility (using the Stanford HIVdb) and HIV subtype are also available.

  4. CHIPS data • A multi-centre cohort study of HIV infected children under care in 59 hospitals in the UK & Ireland since 1996. • 1291 UK children in CHIPS between 1998 and 2006. • 52% female, 77% black African, 52% born abroad, 95% with known vertical infection. • Matched 710 tests in 389 children: 239 children have 1 test, 77 have 2 tests, 35 have 3 tests, and 38 have four or more tests. • Rates of testing consistent across the UK. • 2.6% have documented pMTCT.

  5. Use of resistance testing: by previous ART experience* 43% HIV subtype C, 19% subtype A, and 9% subtype B * ART status can not be defined for 10 tests.

  6. Tests prior to starting ART: by year Starting ART with a resistance test Starting ART without a resistance test PENTA 5

  7. ART naïve: Evidence of transmitted drug resistance? • Children with at least 1 major resistance mutation: Overall rate = 6/65 (9%). * Using Shafer et al. AIDS 2007, Vol. 21.

  8. Tests after starting ART: by year Child with a resistance test and previous ART Child with one HIV-RNA > 1000 c/ml with previous ART

  9. Major resistance mutations by year in tests after the start of ART* (n=635) PI NRTI NNRTI Any class • 36% of children with resistance to NRTIs had mono/dual therapy compared to 13% of those who did not. * Using IAS guidelines Topics in HIV Medicine 2007, Vol. 14.

  10. Prevalence* of resistance to individual drugs in children after the start of ART(n = 336) Intermediate level resistance High level resistance PI NRTI NNRTI * Based only on the last resistance test per child

  11. ART class major resistance* in ART experienced children(n=336) Resistance to 0 classes 1 class 2 classes 3 classes * Based only on the last resistance test per child * Using IAS guidelines Topics in HIV Medicine 2007, Vol. 14.

  12. Triple class resistance in ART experienced children • In CHIPS, 391 children have had triple class exposure. • Of these, 23(5.9%) have known triple class resistance and 137(35.0%) have resistance to two ART classes. • Median (IQR) age at tests showing… triple class resistance: 10.3 (6.0 , 13.3) years. resistance to two ART classes : 9.1 (5.5 , 12.7) years • Half of those with resistance to at least 2 classes were ≥13 years old.

  13. Discussion and Conclusions: Resistance in ART naïve children • There is little use of resistance testing in ART naïve children. Slightly higher use in ART experienced children possibly increasing over time. • Possible evidence of some transmitted resistance from mother to child.

  14. Discussion and Conclusions: Resistance after starting ART • Resistance to NRTIs may reflect use of mono/dual therapy prior to HAART. • Higher resistance to NNRTIs reflects the relatively rapid emergence of resistance to these drugs compared to boosted PIs. • Resistance, in particular triple class, will affect future drug choices for adolescents transferring to adult clinics. Low use of T-20 and Raltegravir in children.

  15. Acknowledgements • CHIPS centres, staff, and children • NSHPC • The UK Collaborative Group on HIV drug Resistance www.chipscohort.ac.uk

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