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8èmes Rencontres Nord-Sud

HIV Drug Resistance in Children. 8èmes Rencontres Nord-Sud. Avelin Aghokeng IRD-UMI233 & University of Montpellier I Yaoundé-Cameroon. Background. Infants can acquired HIV drug resistance (HIVDR) in many ways:. PMTCT interventions (maternal ART & neonatal prophylaxis) .

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8èmes Rencontres Nord-Sud

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  1. HIV Drug Resistance in Children 8èmes Rencontres Nord-Sud Avelin Aghokeng IRD-UMI233 & University of Montpellier I Yaoundé-Cameroon

  2. Background Infants can acquired HIV drug resistance (HIVDR) in many ways: • PMTCT interventions (maternal ART & neonatal prophylaxis). • Transmission of resistant virus from mother to child. • Acquired resistance during dedicated ART. PMTCT ACTION ART ACTION

  3. PMTCT & HIVDR Potential ARV regimens used to prevent mother to child transmission of HIV: A B B+

  4. As a consequence ofPMTCT Infant who become infected despite PMTCT can prematurely acquired drug resistant HIV. Maternal ART (NNRTI based) Infant Prophylaxis Antenatal Infantinfected despite PMTCT At birth and 4-6 wks later Intra-partum Post-partum (breastfeeding)

  5. Arrivé et al., 2007 35.7% NVP-R Prevalence of viral resistance to nevirapine (NVP) in mothers at 4–8 weeks postpartum after single-dose exposure. 4.5% NVP-R

  6. Arrivé et al., 2007 52.6% NVP-R Prevalence of resistance to nevirapine (NVP) in children at 4–8 weeks postpartum after single-dose exposure 16.7% NVP-R

  7. As a consequence ofPMTCT Infants become infected with a resistant virus through transmission of mother resistant virus. Infant infected with resistant HIV Maternal ART (NNRTI based) Acquired HIVDR Transmission of resistant virus • - In Utero • Peri-partum • Via breastfeeding

  8. Persaud et al., 2007 Infant pre-HAART HIV isolates harbor resistance mutations

  9. Persaud et al., 2007

  10. ART in Children & adolescents 2013 UNAIDS Report

  11. Virologic failure Sigaloff et al., Lancet. 2011 Children < 18 years

  12. HIV-1 drug resistance Sigaloff et al., Lancet. 2011 Children < 18 years

  13. Timing of resistance Sigaloff et al., Lancet. 2011 Children < 18 years Early emergence of drug resistance. In up to 75% of cases, HIVDR is acquired before 1 year of ART.

  14. Drug resistance Mutation Sigaloff et al., ARHR. 2013 Drug resistance Profiles • Children aged ≤ 12 years • Failing a first-line ART • 2NRTI + NNRTI 1srt line ART

  15. WHO strategies WHO updated HIV drug resistance early warning indicators and targets – 2012

  16. WHO strategies Surveillance of HIV Drug resistance in children <18 months receiving Antiretroviral Therapy.

  17. Survey Objectives 1. Assess the prevalence of NRTI and NNRTI resistance in HIV-infected children less than 18 months. - with history of exposure to PMTCT - without history of exposure to PMTCT - unknown history of exposure to PMTCT 2. Explore predictors of NNRTI resistance (multicountry pooled analysis).

  18. Materialand ----------------Methods • DBS from child < 18 month. • DBS tested HIV+ for EID. • Child NOT receiving three or more ARV drugs for ART purpose. • Stored < 30 days at room temperature.

  19. Results: Swaziland

  20. Results: Zimbabwe

  21. Pooled analysis By infant age NNRTI Resistance

  22. Pooled analysis by neonatal ART NNRTI Resistance

  23. Conclusion Effective PMTCT intervention is essential to prevent vertical transmission of HIV. High burden of HIV-1 drug resistance observed in children and adolescent. Unexpectedly high HIVDR prevalence levels, up to 23% in children supposed to be unexposed to PMTCT and 50% if exposure was “unknown”. Surveillance of HIVDR remains critical to monitor the impact of scaling-up PMTCT strategies and inform future policy change.

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