TreatmentUpdate
230

March 2019 

Higher levels of dolutegravir in older people not linked to side effects

Most clinical trials testing HIV drugs enroll young and relatively healthy adults. Such studies do not capture the effects of a drug in different populations, particularly people aged 60 and older. As people age, subtle changes occur in their intestines and with the molecules needed to move drugs from the intestine to the blood. Also, the functioning of the kidneys gradually declines with age and their ability to filter substances from the blood is reduced.

Looking in London

A team of scientists at hospitals and research institutes in London, England, conducted a study with people aged 60 to 79 years to assess absorption of dolutegravir as well as possible changes to sleep and cognitive functioning (thinking, memory and information processing).

The team found that the maximum levels of dolutegravir in the blood were significantly greater (by about 25%) in people aged 60 and older compared to people aged 50 and younger who had taken dolutegravir in previous studies. Interestingly, there was no significant effect of elevated levels of dolutegravir on the following:

  • sleep problems
  • feeling drowsy in the daytime
  • fatigue
  • general well-being
  • neuropsychiatric side effects

On some tests, higher concentrations of dolutegravir were associated with subtle improvements in cognitive functioning.

Study details

Researchers planned the study to last for 180 days. Potential study volunteers were required to have an undetectable viral load as a result of their pre-study regimen and once enrolled were switched to the following regimen:

  • Triumeq – a pill containing dolutegravir + abacavir + 3TC

This medication was taken at a dose of one pill once daily in the morning, with or without breakfast.

Participants underwent extensive blood tests and surveys about sleep and other issues on a regular basis.

Researchers enrolled 43 people. Three participants dropped out by the 28th day of the study—two of them moved overseas and the third developed sensitivity to sunlight, likely caused by the study medicines.

This left 40 people in the study whose data could be analysed. By day 180, two other participants withdrew—one because of employment in another city and the other due to sleeping problems. Doctors changed this person’s regimen to a combination of raltegravir + Truvada (tenofovir DF + FTC) and he recovered.

The average profile of the 40 people upon their entry to the study was as follows:

  • 39 men, one woman
  • age – 66 years (participants’ ages were between 60 and 79 years)
  • most participants (83%) were white and the remaining people were of African, Hispanic and Asian descent
  • most participants had what the study team judged as “mild” sleeping problems

The data from the present study were compared to data from a previous study of dolutegravir in 16 people who were aged 50 and younger.

Results

There were changes in sleeping problems as following:

  • Four people who entered the study with a mild degree of insomnia progressed to “moderate” insomnia, according to the researchers. However, this change was not statistically significant.
  • Another person who had insomnia upon entering the study had it resolve with the use of dolutegravir.

Overall, in general, there were no significant changes in assessments of thinking, memory and other cognitive processes during the study.

No serious problems or side effects developed during the study, and the researchers stated that Triumeq was “well tolerated.”

Why did dolutegravir levels increase in older people?

The study team is not certain why dolutegravir levels increased by 25% in older vs. younger people. They speculated that the molecules that the body uses to help carry dolutegravir from the intestine to the blood may have increased with age. However, this needs to be confirmed by a study designed just for that purpose.

Bear in mind

The present study is a very good step forward in understanding the issue of drug levels of dolutegravir in people aged 60 and older. Other pharmaceutical companies should also conduct similar studies with their drugs in this population.

A shortcoming of the present study was its reliance on an overwhelmingly male (98%) group of participants. This needs to be addressed in a future study.

The researchers found that although the concentration of dolutegravir in the blood of people aged 60 and older was 25% greater than in people aged 50 years and younger, there were no significant increases in side effects—particularly in assessments of sleep and cognition.

—Sean R. Hosein

REFERENCE:

Elliot ER, Wang X, Singh S, et al. Increased dolutegravir peak concentrations in people living with human immunodeficiency virus aged 60 and over, and analysis of sleep quality and cognition. Clinical Infectious Diseases. 2019 Jan 1;68(1):87-95.