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8èmes Rencontres Nord-Sud
HIV Drug
Resistance in
Children
Avelin Aghokeng
IRD-UMI233 & University of Montpellier I
Yaoundé-Cameroon
Background
• 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 ACTION
ART ACTION
PMTCT & HIVDR
Potential ARV regimens used to prevent mother to child transmission of HIV:
Mother InfantCD4 ≤ 350 CD4 > 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
A
Infant who become infected despite PMTCT can prematurely acquired drug resistant HIV.
As a consequenceof PMTCT
Infant infected despite
PMTCT
Maternal ART
(NNRTI based)
Antenatal
Intra-partum
Post-partum(breastfeeding)
Infant Prophylaxis
At birth and 4-6 wks later
Arrivé et al., 2007
35.7% 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., 2007
52.6% NVP-R
16.7% NVP-R
As a consequenceof PMTCT
Infants become infected with a resistant virus through transmission of mother resistant virus.
Infantinfected with resistant HIV
Maternal ART(NNRTI based)
Acquired HIVDR
Transmission of resistant virus
- In Utero- Peri-partum- Via breastfeeding
Persaud et al., 2007
Infant pre-HAART HIV isolates harbor
resistance mutations
Persaud et al., 2007
2013 UNAIDS Report
ART in Children & adolescents
Virologic failureSigaloff et al., Lancet. 2011
Children < 18 years
HIV-1 drug resistanceSigaloff et al., Lancet. 2011
Children < 18 years
Timing of resistanceSigaloff 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.
Drug resistance ProfilesDrug resistance MutationSigaloff et al., ARHR. 2013
- Children aged ≤ 12 years
- Failing a first-line ART
- 2NRTI + NNRTI 1srt line ART
WHO strategies
WHO updated HIV drug resistance early warning indicators and targets – 2012
WHO strategies
Surveillance of HIV Drug resistance in children <18 months receiving Antiretroviral Therapy.
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).
Material and ----------------
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.
Results: Swaziland
Results: Zimbabwe
NN
RTI
Resis
tan
ce
Pooled analysisBy infant age
NN
RTI
Resis
tan
ce
Pooled analysisby neonatal ART
Conclusion
1. Effective PMTCT intervention is essential to prevent vertical transmission of HIV.
2. High burden of HIV-1 drug resistance observed in children and adolescent.
3. Unexpectedly high HIVDR prevalence levels, up to 23% in children supposed to be unexposed to PMTCT and 50% if exposure was “unknown”.
4. Surveillance of HIVDR remains critical to monitor the impact of scaling-up PMTCT strategies and inform future policy change.
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