Letermovir in ART-treated HIV-infected Persons

NCT05362916 | Completed DMC

• 1 other identifier: MP-37-2022-8295
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-centre, open-label, randomized, controlled clinical trial to assess the influence of letermovir on gut translocation marker LPS in blood in ART-treated cytomegalovirus (CMV)-seropositive adult people living with HIV (PLWH). The study will explore the influence of letermovir treatment on gut damage, with no intention for label change. Participants (n=60) should have a cluster of differentiation 4 cells (CD4) count greater than 400 cells/µl and a negative viral load. Forty (40) participants will be randomized to receive letermovir (PREVYMIS® 480 mg or 2x240mg orally) in addition to their usual ART, and 20 participants will receive standard of care alone (ART only) for 14 weeks. Study visits will include screening, 2 baselines, followed by follow-up visits at 2 and 4 weeks and at 14 weeks after starting treatment and 12 weeks after end of letermovir treatment to assess a carry-over effect. In an optional sub-study, colonoscopies and colon biopsies will be performed before and after letermovir treatment or standard of care alone to assess gut mucosa inflammation.

Conditions

People Living With HIV

Outcome Measures

Primary Outcomes (1)

• Gut Inflammation

  To assess the influence of CMV replication inhibition with letermovir on gut translocation markers (LPS) in blood of PLWH.

  28 weeks

Secondary Outcomes (4)

• Gut permeability

  28 weeks

• Inflammation markers

  28 weeks

• Anti-CMV immune response

  28 weeks

• CMV DNA detection in gut

  28 weeks

Study Arms (2)

Letermovir

EXPERIMENTAL

40 patients with CMV infection will be treated with Letermovir

Drug: Letermovir

Controls

NO INTERVENTION

20 patients with CMV infection will not be given Letermovir

Interventions

Letermovir DRUG

Participants in the treatment arm will take either 1 tablet of 480mg PO once daily or 2 tablets of 240mg PO once daily.

Also known as: PREVYMIS

Letermovir

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants will be eligible for the study if they meet the following criteria:
• Male or female adults ≥18 years of age.
• Documented HIV-1 infection by Western Blot, Enzyme Immuno Assay (EIA) or viral load assay.
• CMV seropositive (as per clinical lab test).
• On ART for at least 3 years, and stable ART regimen (same prescription) for at least 3 months.
• Undetectable viral load \< 50 copies/ml for the past 3 years. Viral blips in the past 3 years, below 200 copies/ml, are allowed if preceded and followed by a HIV viremia below 50 copies/ml.
• CD4 count \>400 cells/µL of blood
• Able to communicate adequately in either French or English.
• Able to understand and willing to provide written informed consent prior to screening.
• Women of childbearing potential must have a negative serum pregnancy test.
• Women of childbearing potential must agree to use one of the following approved methods of birth control while in the study and until 2 weeks after completion of the study:
• Complete abstinence from penile-vaginal intercourse from the screening period until 2 weeks after study completion.
• Double barrier method (acceptable barrier methods include diaphragm, coil, contraceptive foam, sponge with spermicide, or condom).
• Oral, injectable or implant contraceptives, started at least 30 days before screening, plus one barrier method.
• Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year (not all IUDs meet this criterion) plus one barrier method.

You may not qualify if:

• Patients who are hypersensitive to letermovir or to any ingredient in the formulation of PREVYMIS®, including any non-medicinal ingredient, or component of the container.
• Current AIDS-related event or serious health condition including systemic infections in the last 3 months.
• Severe systemic diseases (e.g. uncontrolled hypertension, chronic renal failure), or active uncontrolled infections including Coronavirus disease 19 (COVID-19) (as tested by PCR).
• Co-infection with active Hepatitis B or C Virus. Current use or have used in the past 3 months: immune-modulatory agents, prophylactic antibiotics, proton pump inhibitors, Metformin or Morphine as these drugs modulate inflammation and/or gut microbiota composition.
• Recent changes in dietary habits, intermittent fasting, chronic constipation or laxative use as these can affect gut microbiota.
• Psychiatric or cognitive disturbance or any illness that could preclude compliance with the study.
• Current participation in an experimental therapy study or receipt of experimental therapy within the last 6 months.
• Women who are planning to become or who are pregnant, or breast-feeding. A score of higher than 8 on a Full AUDIT questionnaire at the screening visit, suggesting an alcohol abuse problem.
• Patients with moderate hepatic impairment combined with moderate or severe renal impairment (CrCl less than 50 mL/min)

Sponsors & Collaborators

• Jean-Pierre Routy: lead

Study Sites (1)

Mcgill University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (1)

• Royston L, Isnard S, Berini CA, Bu S, Lakatos PL, Bessissow T, Chomont N, Klein M, Lebouche B, de Pokomandy A, Kronfli N, Costiniuk CT, Thomas R, Tremblay C, Boivin G, Routy JP. Influence of letermovir treatment on gut inflammation in people living with HIV on antiretroviral therapy: protocol of the open-label controlled randomised CIAO study. BMJ Open. 2023 Jan 23;13(1):e067640. doi: 10.1136/bmjopen-2022-067640.

  PMID: 36690406 DERIVED

MeSH Terms

Interventions

letermovir

Study Officials

• Carolina A Berini, BSc, PhD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Director of the Chronic Viral Illness Service Division of Hematology and Chronic Viral Illness Service Louis Lowenstein Chair in Hematology & Oncology Professor of Medicine, McGill University

Model Details: Multi-centre, open-label, randomized, controlled clinical trial

Study Record Dates

• First Submitted: April 22, 2022
• First Posted: May 5, 2022
• Study Start: September 26, 2022
• Primary Completion: January 27, 2025
• Study Completion: January 27, 2025
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)