PENTA 20 (Odyssey)

Virological failures and genotypic resistance in children and adolescents randomised to dolutegravir-based ART vs. standard-of-care in the ODYSSEY trial

Tags: | July 29th, 2021

Authors: C. Kityo, E. White, A. Turkova, H.A Mujuru, I. Nankya, B. Wynne, S. Ali, A. Kekitiinwa, A. Lugemwa, E. Kaudha, A. Liberty, H. Cassim, M. Archary, M. Cotton, L. Barlow-Mosha, T.R Cressey, C. Ngampiyasakul, U. Srirompotong, O. Behuhuma, Y. Saidi, A. Bamford, R. Kobbe, P. Rojo, C. Giaquinto, D. Gibb, D. Ford

Published in: IAS 2021

 

Abstract

Background: ODYSSEY demonstrated superiority of dolutegravir (DTG) based ART versus standard-of-care (SOC) in children ≥14kg starting first- or second-line. We evaluate drug resistance by 96 weeks.

Methods: Virological failure (VF) was defined as confirmed viral load (VL)≥400c/mL after week 36 or lack of virological response at week 24 with ART switch. Children with VF were tested for post-failure resistance (major IAS mutation); if resistance was identified, a baseline sample was sequenced. The proportion with emergent resistance post-failure was estimated in those exposed to each drug class in ODYSSEY.

Results: 311 children started first-line ART (154 DTG,157 SOC[92% efavirenz]) and 396 second-line (196 DTG,200 SOC[72% lopinavir/r,25% atazanavir/r]). On first-line, 11(7%) DTG vs 30(19%) SOC experienced VF by 96 weeks, and on second-line, 31(16%) DTG vs 40(20%) SOC. First-line: no new DTG or NRTI resistance on first-line DTG versus estimated 62% and 88% children with new NRTI and NNRTI resistance respectively among failures in SOC (Table). Second-line: no new resistance to NRTIs on DTG vs estimated 9% among failures in SOC. One child (estimated 3%) with VF on PIs had new PI resistance and two children (100%on NNRTIs had new NNRTI resistance. 4(18%) with VF on DTG had INSTI mutations.

Conclusion: ODYSSEY demonstrated that DTG has a high genetic resistance barrier and prevents emergent resistance to NRTIs in children. We identified no post-failure resistance on first-line DTG, significantly less than first-line SOC. On second-line DTG, there was no new NRTI resistance, however 4 children developed new INSTI resistance, highlighting the need for ongoing adherence support among children.

 

Table: Genotypic resistance in the ODYSSEY trial

First-line Second-line
DTG SOC DTG vs. SOC DTG SOC DTG vs. SOC

 

Children with resistance post-failureƪ 

 

NRTI 0/11 0% 18/29 62% p<0.001 20/28 71% 28/39 72% P=0.97
NNRTI 0/11 0% 27/29 93% p<0.001 21/28 75% 35/39 90% p=0.18
PI 0/11 0% 0/29 0% 2/28 7% 2/39 5% p=1.00
INSTI 0/10 0% 4/22 18%

 

Children and estimated proportion with emergent resistance post-failure~

 

NRTI 0 0% 13 62% 0 0% 3 9%
NNRTI 18 88% 2 100%
PI 1 3%
INSTI 0 0% 4 18%

 

ƪPost-failure resistance up to week 96, using the latest sample with VL≥1000c/mL after VF and prior to ART switch. % with resistance post-failure, of those with post-failure resistance test available

~Among those with VF and exposed to drug-class, estimated assuming same proportion of new resistance in those with and without available baseline test

 

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