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A small study explores dolutegravir + 3TC in heavily treatment-experienced patients

The combination of dolutegravir + 3TC (sold as Dovato) is increasingly used as an HIV treatment option. As it contains two drugs (instead of the standard three, which has been the historical norm since 1996), doctors are cautious in their use of this combination. It is not generally used in people who have HIV that is resistant to 3TC or other drugs. Resistance to 3TC is relatively common.

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The laboratory of the late McGill University scientist Mark Wainberg found that while HIV can develop resistance to 3TC, such viruses do not replicate as quickly as non-3TC-resistant virus.

In a study called Solar-3D, researchers in the U.S., independently of any pharmaceutical company, recruited consecutive participants between 2019 and 2020 for a trial. This study was initially meant to be 96 weeks long but has been extended to 144 weeks. Participants were required to have at least one of the following:

  • taking ART but never achieved an undetectable level (less than 50 copies/mL)
  • if they did achieve an undetectable viral load, then their viral loads subsequently rose above 200 copies/mL
  • documented resistance by HIV to one or more medicines
  • any CD4+ count

At the start of the study, the average profile of participants was as follows:

  • age – 58 years
  • length of time since HIV diagnosis – 25 years
  • length of time on ART – 22 years
  • number of previous regimens – 7
  • duration of HIV suppression – 13 years
  • lowest-ever CD4+ count – 190 cells/mm3

The mutation code named M184V/I is associated with resistance to 3TC by HIV. At the time they entered the study, 37% of participants had this mutation detectable in their HIV reservoir. Researchers called this “historical M184V/I.”

About half of the participants were taking Triumeq (a combination of dolutegravir + 3TC + abacavir) prior to entering the study. Many of the remaining participants were taking complex regimens.

About half of the participants had no historical resistance to 3TC.

Results

At week 144, 94% of participants had an undetectable (less than 50 copies/mL) viral load, as follows:

  • 37 out of 39 people with historical M184V/I mutation
  • 36 out of 39 people without this mutation

These results were not statistically different.

When researchers analyzed blood samples with a more sensitive threshold of 20 copies/mL, they found that the proportions of people who achieved an undetectable viral load were distributed as follows:

  • with M184V/I mutation – 68% were undetectable
  • without M184V/I mutation – 64% were undetectable

Among people with the M184V/I mutation, eight died because of the following complications unrelated to the study medicines:

  • deterioration of the heart muscle in a person who was 69 years old
  • cardio-respiratory arrest in a person who was 52 
  • stroke in a person who was 72 
  • anal cancer in a person who was 59 
  • congestive heart failure in a person who was 74 
  • overdose on methamphetamine in a person who was 48 
  • chronic kidney disease in a person who was 73 
  • abnormal heart rhythms and congestive heart failure in a person who was 62 

In people without M184V/I there were two deaths: one from suicide and one possibly from suicide.

More people without M184V/I left the study and changed regimens to injectable cabotegravir + rilpivirine (Cabenuva). 

The researchers found that most adverse events were mild to moderate. There were low rates of depression (three people), headache (two people) and sleeping problems (two people).

One person prematurely left the study because of vertigo.

Bear in mind

This was not a randomized clinical trial. It was a relatively small study and, therefore, the findings are not applicable to the average person with HIV. However, it has found a signal that the presence of M184V/I mutation may not necessarily be a barrier to future successful treatment with the combination of dolutegravir + 3TC. Although these findings are promising, they need to be better explored in a large randomized clinical trial.

—Sean R. Hosein

REFERENCE:

Blick G, Cerreta-Dial E, Mancini G, et al. No confirmed virological failures (CVF) for 144 weeks when switching 2-/3-/4-drug ART to DTG/3TC in heavily treatment-experienced PLWHA with prior M184V/I and virological failures (VF) in the prospective SOLAR-3D study. 25th International Conference on AIDS, Munich, Germany, 22-26 July 2024. Abstract SS0403LB.