Post on 29-Dec-2015
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
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.
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
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