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Title
High rates of long-term HIV RNA re-suppression after virological failure on dolutegravir in the ADVANCE trial
Presenter
Andrew Hill
Authors
B. Bosch1, S. Sokhela1, G. Akpomiemie1, N. Chandiwana1, W.D.F. Venter1, B. Simmons2, K. McCann3, M. Mirchandani3, A. Hill4
Institutions
1Ezintsha, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa, 2London School of Economics and Political Science, LSE Health, London, United Kingdom, 3Imperial College London, Faculty of Medicine, London, United Kingdom, 4University of Liverpool, Department of Pharmacology and Therapeutics, Liverpool, United Kingdom

BACKGROUND: WHO Guidelines currently recommend switching to next-line antiretroviral treatment (ART) for individuals with sustained HIV RNA viral load (VL)=1000 copies/mL despite adherence counselling. However, individuals can re-suppress after adherence counselling, with no change in treatment. We compared rates of virological failure and re-suppression in the ADVANCE trial of first-line treatment in South Africa.
METHODS: In ADVANCE, 1053 treatment-naive individuals were randomised to TAF/FTC/DTG, TDF/FTC/DTG or TDF/FTC/EFV for 192-weeks. All individuals with VL >1000 copies/mL received enhanced adherence counselling within 4 weeks. Time to first VL=50 copies/mL was compared between treatment arms using Kaplan-Meier methods. Rates of virologic failure (any VL=1000 copies/mL after Week-24) were then compared. For individuals with virological rebound, rates of VL re-suppression <50 copies/mL were compared with follow up to Week 192.
RESULTS: Time to suppression =50 copies/mL was significantly shorter in the combined DTG arms (4 weeks) compared to the EFV arm (12 weeks); (log-rank p<0.001). The proportion with virologic failure was similar across arms (combined DTG 87/702 [12%] vs EFV 33/351 [9%]; log-rank p=0.343). However, more individuals on EFV remained viraemic prior to failure (12/33 [36%] compared with DTG 10/87 [11%]; p=0.002). For individuals with rebound =1000 copies/mL after Week 24, time to re-suppression was significantly shorter for DTG (12 weeks) than EFV (26 weeks); log-rank p<0.001. There were no cases of treatment-emergent DTG resistance in the individuals with virological failure =1000 copies/mL.


CONCLUSIONS: In ADVANCE, episodes of viraemia=1000 copies/mL were seen at similar rates across treatment arms. However, HIV RNA re-suppression after viraemia =1000 copies/mL was significantly more likely for individuals taking either TDF/FTC/DTG or TAF/FTC/DTG, compared with TDF/FTC/EFV. Long-term follow-up suggests most individuals on continued DTG after viraemia elevation can re-suppress with enhanced adherence counselling. These results question the need for switch to 2nd line PIs after VF on DTG.