Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance

AIDS Res Ther. 2021 Sep 8;18(1):58. doi: 10.1186/s12981-021-00384-6.


Objective: The DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance.

Design: Post hoc analysis of a randomized trial.

Methods: Main inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response).

Results: The analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed.

Conclusions: DTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs.

Trial registration: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; .

Keywords: Darunavir; Dolutegravir; HIV drug resistance; Integrase inhibitors; Protease inhibitors.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents* / therapeutic use
  • Darunavir / therapeutic use
  • Drug Resistance
  • Female
  • HIV Infections* / drug therapy
  • HIV-1* / genetics
  • Heterocyclic Compounds, 3-Ring
  • Humans
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Pyridones


  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir
  • Darunavir

Associated data

  • EudraCT/2015-000360-34