Dolutegravir monotherapy still not recommended: 4-year follow up in early-treated durably suppressed participants

Simon Collins, HIV i-Base

Several years ago, early switch studies of dolutegravir monotherapy were quickly stoppedm due to viral rebound with INSTI class resistance in some participants. [1]

Treatment guidelines also specifically excluded dolutegravir monotherapy as an option in any circumstances.

The Early-Simplified study however, using dolutegravir monotherapy in early infection, continued, and has reported follow-up to four years. [2]

This study included 101 participants who had started ART within six months of infection and who had been suppressed on ART for a median of 3.5 years. Participants were randomised (2:1) to either switch to dolutegravir monotherapy or continue their current ART.

Surprisingly – and luckily – no cases of viral rebound occurred over this extended time. These results still do not suggest that dolutegravir monotherapy should be repeated or used, but they add to our knowledge about the complexity of treatment.

The researchers rightly conclude that the high efficacy and safety of dual therapy using dolutegravir and lamivudine make the current data of historical value only. Also, that monotherapy should not be used in any setting.

An editorial comment in the same publication notes the intriguing results linked to participants having started ART soon after infection when the CD4 count was still high and the viral reservoir remained relatively small. [3]

Participants had also maintained undetectable viral load for a median of 3.6 years before switching to monotherapy.


  1. Collins S, Dolutegravir monotherapy studies halted due to integrase resistance: dual therapy studies continue. HTB (27 February 2017).
  2. West E et al. Sustained viral suppression with dolutegravir monotherapy over 192 weeks in patients starting combination antiretroviral therapy during primary HIV infection (EARLY-SIMPLIFIED): a randomized, controlled, multi-site, non-inferiority trial, Clinical Infectious Diseases, 2023, ciad366.
  3. Hocqueloux L and Parienti J-J. Dolutegravir monotherapy possibly boosted by highly active natural immunity, Clinical Infectious Diseases, 2023; ciad365. (20 June 2023).

This report was first published on 12 November 2023.

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