À propos de l'étude

This pilot trial will assess whether letermovir, an antiviral for cytomegalovirus (CMV), can improve gut health and reduce systemic inflammation in people living with HIV who take antiretrovirals (ART). Overall, the study aims to determine how to lower the risk of HIV-related comorbidities due to chronic inflammation, like heart disease and cognitive disorders.

About the Problem

Cytomegalovirus (CMV) is a type of herpes virus that is extremely common across the world and even more so among people living with HIV. The virus is harmless to most healthy people, but can cause problems for people who are immunocompromised. In people living with HIV, CMV infection is associated with increased systemic inflammation and HIV-related comorbidities. Both HIV and CMV increase permeability of the gut, allowing microbes from the digestive system to leak into the bloodstream, leading to inflammation. Because ART effectively controls HIV replication and stops its negative effect on the gut, researchers think that CMV may be a primary driver of the ongoing gut permeability and persistent systemic inflammation seen in people living with HIV on ART. CMV can also decrease the response to vaccines in people living with HIV. This is because the immune system is focused on fighting both HIV and CMV and doesn’t have the resources to properly respond to vaccines, as well as other pathogens.

Antiviral medications for CMV can decrease immune activation in people living with HIV, but older medications are not safe for long-term use. A new anti-CMV drug, letermovir, was approved in 2017 for transplant patients and is much safer than previous drugs.  CTNPT 047 is one of only two studies in the world that is testing this drug in people living with HIV. The study aims to understand how CMV affects people living with HIV and whether letermovir can reduce systemic inflammation and allow the damaged gut cells to repair.

Approche de l'étude

This study is enrolling 60 patients living with HIV on ART. Forty patients will be randomized to receive letermovir once daily for 14 weeks, in addition to their regular ART regimen. Twenty participants will be randomized to continue taking ART only. Including the screening visit, there will be seven site visits over the course of the study where participants will have blood samples taken. Researchers will measure the levels of bacterial fragments (originating from the gut) in the blood and compare these levels between the letermovir and ART-only groups. They will also compare other markers of gut permeability, inflammation, and CMV-related immune response. There is also an optional substudy that participants can enroll in where colonoscopies and colon biopsies will be performed in two separate visits to directly assess changes in gut inflammation.

Critères d'admissibilité

Requis

To be eligible for the study you must be:

  1. 18 years of age or older,
  2. CMV positive,
  3. HIV positive,
  4. on ART for at least 3 years,
  5. on the same ART medications for at least 3 months,
  6. have an undetectable viral load (the quantity of HIV virus in your blood must be less than 50 copies/ml, except for one blip not higher than 200 copies/ml per year in the last 3 years) for at least 3 years,
  7. have a CD4 count of more than 400.

Interdit

You will not be able to take part in the study if you:

  1. have an active co-infection with hepatitis B or C virus
  2. have any underlying conditions, such as diabetes, cardiovascular disease or renal dysfunction (a study doctor or nurse will review your medical history to ensure you do not have a health condition that will make you unsuitable for the study)
  3. are taking, or plan to take, some drugs and herbal supplements such as antibiotics, metformin, morphine and derivates, chemotherapeutics, niacin, anticoagulant (including Warfarin, Coumadin® and Jantoven®), pimozide, ergot alkaloids, cyclosporine (because of known interactions with letermovir)
  4. are taking some specific HIV medications: darunavir, efavirenz, etravirine and nevirapine (also due to interactions)
  5. are unwilling to disclose to a study nurse or doctor all prescription drugs, natural health products (including supplements or herbal products), pre- or pro-biotics or other non-prescription drugs (including cannabis and street drugs) that you are taking or plan on taking
  6. alcohol is not prohibited but participants will be asked about using alcohol, and excluded if alcohol abuse is suspected
  7. have a pre-existing condition that could prevent study compliance such as street drug abuse or psychiatric illness
  8. are taking part in another clinical trial or have done so in the past 3 months
  9. are a female who is pregnant, planning on becoming pregnant, or who is breast-feeding

Pour plus de renseignments

If you would like to take part in this study or want more information, please contact Dr. Léna Royston.

Co-Investigator
Dr. Léna Royston, M.D., PhD
Research Institute of the McGill University Health Centre
1001 Boulevard Decarie
Montreal, QC, H4A3J1

Principal Investigator

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Participating Sites

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