High rates of long-term HIV RNA re-suppression after virological failure on dolutegravir in the ADVANCE trial

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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 the 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 randomized to TAF/FTC/DTG, TDF/FTC/DTG or TDF/FTC/EFV for 192weeks. All individuals with VL >1000 copies/ml received enhanced adherence counselling within 4 weeks. Time to first VL ≤50copies/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. EFV33/351 [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 ≥1000copies/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, HIVRNA 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 that most individuals on continued DTG after viraemia elevation can re-suppress with enhanced adherence counselling. These results question the need for switch to second-line PIs after VF on DTG.

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