Human immunodeficiency virus 1
This is a randomized, parallel, and controlled, open-label clinical trial. A 1:1 randomisation procedure will assign the participant to receive either letermovir 480mg PO OD (letermovir oral formulation of 240mg), or no additional intervention, as per standard care for 12 weeks with a further 12 weeks of follow-up, off trial drug. Biopsies will be taken at Day 1, Week 12 and Week 24. Blood sampling at each visit. All participants will remain on their baseline ART regimen (standard treatment) throughout the trial. Randomized participants will receive a 4-week supply of trial medication on Day 1 (Visit 2). Participants will be instructed to take their first dose of all trial medication at least within 24 hours of the Day 0 trial visit. Participants on the letermovir arm will be instructed to take letermovir 480 mg once a day orally, with or without food, at approximately the same time each day for 12 weeks with a further 12 weeks of follow-up, off trial drug. Sealed EnvelopeTM web-based randomisation system will be used. Block randomisation will be used. Investigators randomise patients by completing an on-screen form with patient details, stratification factors, inclusion and exclusion criteria. Investigators are immediately shown the treatment allocation.
1. Is HIV-1 antibody positive with a plasma HIV-1 RNA ≤50 copies/mL for greater than 12 months 2. ≥50 years of age of any gender 3. Females of childbearing potential who agree to avoid pregnancy for the duration of the trial and follow methods of contraception as detailed in section 7.1 4. Has a nadir CD4 of ≤200 cells/mm3 prior to screening 5. Has been on antiretroviral therapy for ≥ 6 months 6. Has documented CMV IgG seropositivity within one year of trial screening 7. Has an undetectable (≤168 international units/mL) CMV Deoxyribonucleic acid (DNA) within 14 days prior to randomisation 8. Laboratory parameters are not clinically significant as determined by the investigator 9. The participant (or legally acceptable representative, if applicable) has provided written informed consent for the trial and Future Biomedical Research
1. Has a history of ulcerative colitis or Crohn’s disease or active colitis within 6 months prior to randomisation 2. Has a history of CMV end-organ disease within 6 months prior to randomisation 3. Has significant hypersensitivity or other contraindication to any of the components of the trial drug as described in the SmPC 4. Has a detectable HCV RNA or hepatitis B surface antigen (HBsAg) within 90 days prior to randomisation 5. Has a history of malignancy ≤5 years prior to signing informed consent 6. Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 90 days after the last dose of trial therapy 7. Has received within 7 days prior to screening any of the following: ganciclovir; valganciclovir; foscarnet; acyclovir (≥ 3200 mg PO per day or ≥25 mg/kg IV per day); valaciclovir (≥3000 mg PO per day) or famciclovir (≥1500 mg PO per day). 8. Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this trial or is anticipated to need them during the trial