A Phase 2 interventional study of Letermovir in HIV, sponsored by University College, London. Not yet recruiting. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2024-10-04.
Sponsored by University College, London · Phase 2, Interventional, and Prevention
People living with HIV (PLWH), even with an undetectable viral load (VL) on antiretroviral treatment (ART), develop health conditions, such as heart disease, diabetes, various cancers, and conditions that can affect the brain, more commonly than the general population.
These conditions occur earlier in PLWH compared to HIV negative individuals with similar lifestyles. Ongoing inflammation in the body despite antiretroviral therapy is thought to be contributing to the development of these conditions that can affect healthy ageing in PLWH.
Cytomegalovirus (CMV) is a very common infection in PLWH and is an important driver of inflammation in the body that can affect the function of the immune immune cells in the body (defense system) causing unwanted activation and damage of the gut making it more leaky. A drug with potent activity against CMV called valganciclovir has previously shown to reduce this potentially damaging inflammation in the body.
In this study, the investigators want to investigate if a new drug called Letermovir, in combination with HIV treatment, will prevent CMV from replicating (multiplying), and thereby reduce inflammation in the body. Letermovir has received approval to prevent CMV from multiplying in patients receiving bone marrow transplants. It has been shown to have a more favourable side-effect profile compared to other available drugs and is predicted to interact little with anti-HIV drugs.
The aim of this study is to find out if the letermovir is safe and effective in reducing CMV related immune activation and inflammation PLWH. These findings will be used to help us design larger studies to identify individuals who would benefit most from this treatment to prevent the development of health conditions that can affect their quality of life.
6,687 studies on the registry are indexed under Infections; 807 are open to participants now.
This study's planned enrollment of 36 is below the median of 120 across 4,200 interventional studies indexed under Infections.
Browse Infections studies →University College, London is the lead sponsor of 632 studies on the registry; 145 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Main Exclusion criteria:
Letermovir 480mg PO once daily
Drug: Letermovir
Standard of care - No intervention
Letermovir 480mg PO once daily
Change in activation in global CD8 T cells in response to letermovir.
To assess the effect of CMV replication inhibition with letermovir on activated (HLADR+CD38+) CD8 T cell percentage using flow cytometry analysis at specified time frames. Measurement: Measured by flow cytometric analysis.
Time frame: Baseline, weeks 4, 8, 12, 16 and 24
Quantitative analysis of T cell subsets/detailed phenotypic profile will be performed as part of the exploratory analysis
Quantitative analysis of T cell subsets/detailed phenotypic profile will be performed as part of the exploratory analysis
Time frame: Baseline, weeks 12 and 24
Characterization of NK profile and function in response to Letermovir
To assess the effect of CMV replication inhibition with letermovir on NK cell phenotype and cytokine production (IFN-g/TNF) via flow cytometry. Measurement: Measured by flow cytometric analysis.
Time frame: Baseline, weeks 4, 8, 12, 16 and 24
High resolution characterization of cells that fall between the innate and adaptive responses
To assess the effect of CMV replication inhibition with letermovir on NK-like cells (CD56+CD3+) at specified time points. Measurement: Measured by flow cytometric analysis.
Time frame: Baseline, weeks 12 and 24
Determine the extent of CMV and HIV replication in the gut of HIV-positive individuals and how impacted by intervention
To assess CMV DNA and HIV RNA in gut biopsies and the effect of intervention. Measurement: Measured by quantitative PCR analysis and in situ hybridisation.
Time frame: Baseline, weeks 12 and 24
Assessment of integrity of the intestinal barrier and how impacted by intervention
To assess the influence of CMV replication inhibition with letermovir on intestinal barrier integrity in gut biopsies. Measurement: Measured by immunohistochemistry of biopsy samples for zonula occludens-1 (ZO-1).
Time frame: Baseline, weeks 12 and 24
Assessment of markers of systemic inflammation and how impacted by intervention
To assess the influence of CMV replication inhibition with letermovir on inflammatory cytokines/chemokines (IL-1, IL-6, IP10, TNF-a), sTNFRII, microbial products/activation (LPS, sCD14, CRP), intestinal damage marker (iFABP), vascular dysfunction markers (sICAM-1, sVCAM-1) in the blood of people with HIV. Measurement: Measured by ELISA.
Time frame: Baseline, weeks 4, 8, 12, 16 and 24
Higher resolution analysis of specific responses to peptide level and how impacted by intervention
To assess the influence of letermovir on CMV and HIV-specific T cell responses to peptide stimulation via multiparameter intracellular cytokine staining. Expression of cytokines, such as IFN-γ, TNF and IL-2, and activation markers will be measured via flow cytometry in conjunction with established phenotypic and memory markers. Measurement: Measured by flow cytometric analysis
Time frame: Baseline, weeks 4, 8, 12, 16 and 24
Standard molecular analyses of proviral and HIV transcript quantitation, both surrogate markers of persistent infection
To assess the influence of CMV replication inhibition with letermovir on HIV DNA and Cell-associated RNA Measure: Measured by quantitative real-time PCR and droplet digital PCR (ddPCR).
Time frame: Baseline, weeks 4, 8, 12, 16 and 24
No study locations are listed for this record.
Plan to share: No
This study is not yet recruiting, as verified in Oct 2024. You cannot join it, but the record below documents what was studied.
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University College, London