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.