8èmes Rencontres Nord-Sud Avelin Aghokeng IRD-UMI233 & University of Montpellier I Yaoundé-Cameroon Avelin Aghokeng IRD-UMI233 & University of Montpellier I Yaoundé-Cameroon

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

Potential ARV regimens used to prevent mother to child transmission of HIV: CD4 ≤ 350CD4 > 350 HAART start at diagnosis- AZT start 14 weeks’ gestation. - Single dose NVP during labor and initiation of AZT/3TC. - Daily AZT/3TC for 7 days post- partum. NVP initiated at birth - Until 1 wk after BF stopped. - Or for 4-6 wks in case no BF HAART start at diagnosis and for life. HAART start 14 weeks’ gestation and until delivery or 1 wk after BF stopped. NVP or AZT initiated at birth for 4-6 wks. HAART start at diagnosis and for life.NVP or AZT initiated at birth for 4-6 wks. B+ B B A A

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

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

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

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

Infant pre-HAART HIV isolates harbor resistance mutations

2013 UNAIDS Report

Children < 18 years

Early emergence of drug resistance. In up to 75% of cases, HIVDR is acquired before 1 year of ART.

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

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

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

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).

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. 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.

NNRTI Resistance Pooled analysis By infant age

NNRTI Resistance Pooled analysis by neonatal ART