Human immunodeficiency virus 1 Infections and Infestations HIV
Conditions
Interventions
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 formulati
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
50 Years to 100 Years
Inclusion criteria
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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
United Kingdom
Contacts
Public ContactMargaret Johnson
Outcome results
None listed