A pilot, randomized, open-label, non-active comparator controlled clinical trial to evaluate the effects of letermovir prophylaxis on T-cell immune activation in participants with treated HIV-1 Infection

INTERVENTION: 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. CONDITION: Human immunodeficiency virus 1 ; Infections and Infestations ; HIV PRIMARY OUTCOME: Percentage of activated CD8 T cells (CD38+HLADR+) measured in PBMC in response to letermovir at baseline, weeks 4, 8, 12, 16 and 24 SECONDARY OUTCOME: 1. The change in the off‐study drug period between week 12 and week 24 in the percentage of activated CD8 T cells (CD38+HLADR+) measured in PBMC. ; 2. The number and percentage of activated CD4 and CD8 T cells (CD38+HLADR+) measured in PBMCs at weeks 0, 4, 8, 12, 16 and 24; 3. The number and percentage of activated CD4 and CD8 T cells (CD38+HLADR+) measured in colorectal biopsies at weeks 0, 12 and 24; 4. Markers of immune activation, in CD8 and CD4 T cell subsets and NK cells, measured in PBMC at weeks 0, 4, 8, 12, 16 and 24; 5. Markers of immune activation, as above measured in colorectal biopsies at weeks 0, 12 and 24; 6. Markers of soluble inflammatory markers, namely IL‐1, IL‐6, IP‐10, TNF‐a, sTNFRII, LPS, sCD14, CRP, iFABP, sICAM‐1, sVCAM‐1, measured in plasma at weeks 0, 4, 8, 12, 16 and 24.; 7. Quantification of CMV DNA levels in blood and saliva measured at weeks 0, 4, 8, 12, 16 and 24.; 8. Levels of CMV DNA, HIV‐1 RNA and intestinal tight junction integrity measured in colorectal biopsies at weeks 0, 12 and 24.; 9. Safety defined as Adverse Events and Serious Adverse Events by group INCLUSION CRITERIA: 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