Does changing integrase inhibitors help reduce sleeping problems?

Integrase inhibitors are a cornerstone of HIV treatment (antiretroviral therapy, ART) in the current era. Examples of integrase inhibitors that are used today include the following:

• bictegravir (in Biktarvy)
• dolutegravir (in Dovato, Juluca and Triumeq)
• raltegravir

Most people tolerate integrase inhibitors well. However, there are reports that a small minority of people develop sleeping problems when they use this class of anti-HIV drugs.

A team of researchers in the UK used MRI scans of the brain (functional MRI) to get a sense of oxygenation of different parts of the brain and how they were communicating with each other. 

For their study, the researchers sought to enroll at least 40 people who were taking dolutegravir-containing regimens and who had undetectable viral loads. They assessed sleep behaviours, quality of life, craving for food, insomnia, fatigue and sleep quality with validated questionnaires. Participants also underwent functional MRI at the start of the study and 120 days later. Researchers also took blood samples to analyze proteins linked to inflammation, such as IL-6 (interleukin-6) and neopterin.

Due to the COVID-19 pandemic, researchers were only able to enroll 19 participants, all men who had insomnia and were taking a dolutegravir-based regimen. Participants were then divided into two groups as follows:

• 7 participants were assigned to switch to a bictegravir-based regimen (in practice this would entail taking Biktarvy—a combination of bictegravir, TAF + FTC in one pill)
• 12 participants were to remain on dolutegravir-based HIV treatment

A brief average profile of the men at the time they entered the study was as follows:

• age – 55 years
• length of HIV diagnosis – 11 years
• CD4+ count – 600 cells/mm³
• duration of pre-study ART – 41 months
• commonly used pre-study regimens: Triumeq (dolutegravir + abacavir + 3TC); dolutegravir + Truvada; dolutegravir + 3TC (Dovato) 

All participants had high levels of insomnia.

Results

Researchers found that self-reported sleep quality improved in people who were switched to bictegravir. MRI scans confirmed that their brain activity resembled that of people who had restful sleep. 

The switch in treatment had no impact on blood proteins associated with inflammation.

Bear in mind

This was a very small study, and its findings are not definitive. A much larger study is required to confirm its findings. The study had several shortcomings, such as a lack of placebo and no female participants.

There is also an issue that could have inadvertently biased the study results. Many participants (12) were taking a regimen that contained abacavir. This drug was developed in the early to mid-1990s and was designed to enter the brain to suppress HIV there. In that era, before effective HIV therapy was available, many people experienced brain-related complications such as HIV-related brain injury and reduced memory and cognitive functioning. Unfortunately, reports suggest that some people can experience sleeping problems when using abacavir. Future insomnia studies need to take this into account.

—Sean R. Hosein

REFERENCE:

Henderson M, Alford K, Doyle N, et al. A pilot study assessing changes in cerebral function parameters in persons with insomnia switching integrase inhibitors. 25^th International Conference on AIDS, Munich, Germany, 22-26 July 2024. Abstract OAB3605.