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.