THE NEVEREST STUDYTHE NEVEREST STUDYAT AT

RAHIMA MOOSA MCHRAHIMA MOOSA MCH

Ashraf Coovadia Adjunct Professor

Enhancing Childhood HIV Outcomes(Wits Paediatric HIV Clinics)

Rahima Moosa Mother and Child Hospital

University of the Witwatersrand

Rahima Moosa Mother and Child HospitalHIV Research Unit

Research PCR testing of infants 2001/2002

(Prof Gayle Sherman) Earlier Infant Diagnosis Study

underway (Prof Gayle Sherman) 2008 COPE Pregnant Women on HAART IeDEA

NEVERESTRationale

PMTCT programmes globally using sdNVP

Simple, effective and cheap Downside is the issue of NVP resistance ? Impact on future treatment efficacy

with an NNRTI-containing regimen Research required to answer the

question for both women and children

NEVEREST 1

Objective Whether there are long-lasting effects

of exposure to sdNVP treatment on virologic response to NNRTI–based

therapy among HIV–infected women.

NEVEREST 1 EXPOSED Group - 94 HIV-infected

women who had received sdNVP (18–36 months earlier)

UNEXPOSED Group - 60 unexposed, HIV-infected women who had been pregnant (12–36 months earlier)

NEVEREST 1 VL measured at regular intervals Time to viral Suppression (VL <50

cpm) and confirmed Rebound (VL >400 cpm) were compared.

Drug resistance was assessed using K103N allele–specific real-time PCR assay and population sequencing.

NEVEREST 1 97.5% of Exposed women and 91.3% of Unexposed women achieved

viral suppression by week 24 (P=0.21) 19.4% of Exposed women and 15.1% of Unexposed women

experienced viral rebound within 78 weeks (P=.57) after treatment

NEVEREST 1

60.9% of women for whom K103N was detected did not experience viral suppression or

experienced viral rebound, compared with

15.1% of women for whom K103N was not detected (P< .001)

CONCLUSION Exposure to sdNVP in the prior 18–36

months was not associated with a reduced likelihood of achieving and sustaining viral suppression while receiving NNRTI-based therapy.

However, women with minority K103N mutations before treatment had a reduced durability of virologic suppression.

PUBLICATIONS 44

462 ° CID 2009:48 (15 February) ° HIV/AIDS

NEVEREST 2 Treatment options for HIV-infected children are

limited Many children in resource-limited settings have

been exposed to sdNVP Guidelines recommend starting PI-based

regimens in infants No data on whether or not we need to sustain PI

regimen indefinitely Investigation of a switch strategy is warranted

given concerns around cost and long-term toxicity of PI-based regimens

NEVEREST 2

ObjectiveTo examine the efficacy of switching

from a PI-based regimen to an NNRTI-based regimen in children

previously exposed to sdNVP

Study designsdNVP-exposed childrenMeet criteria for ARVs6 weeks – 24 months of age

Start RTV or LPV/r, 3TC, d4TSuppressed <400 cpm> 3 months by 52 weeks

Eligible for randomization

Stay on LPV/r Switch to NVP

By 52 weeks post-random<50 cpm

By 52 weeks post-random<50 cpm

PUBLICATIONS

AIDS 2009, 23:000-000

TRANSLATION The impact this has made

Allowed us to impact on PMTCT guidelines locally (and hopefully internationally)

How has this work has developed into other research or practice and what you expect to accomplish in the years to come

Plan to continue work on children exposed to sdNVP and investigate switch strategies at a later age.

Optimal regimens for children who are co-treated for TB Optimal PMTCT regimens Adherence strategies

ACKNOWLEDGEMENTSCo-Investigators Louise Kuhn, Tammy Meyers, Gayle ShermanSub-Investigator – Renate Strehlau, Leigh MartensThe Principal Funders – STF, NIH (Archie Smuts, Sebastian Wanless,Prof Lynne Mofenson)The Gauteng Department of HealthThe staff and patients on the NEVEREST studyThe collaborators