CTNPT 047: Letermovir in ART-treated HIV-infected persons

About The Study

This pilot trial will assess whether letermovir, an antiviral for cytomegalovirus (CMV), can improve gut health and reduce systemic inflammation in people living with HIV who take antiretrovirals (ART). Overall, the study aims to determine how to lower the risk of HIV-related comorbidities due to chronic inflammation, like heart disease and cognitive disorders.

About the Problem

Cytomegalovirus (CMV) is a type of herpes virus that is extremely common across the world and even more so among people living with HIV. The virus is harmless to most healthy people, but can cause problems for people who are immunocompromised. In people living with HIV, CMV infection is associated with increased systemic inflammation and HIV-related comorbidities. Both HIV and CMV increase permeability of the gut, allowing microbes from the digestive system to leak into the bloodstream, leading to inflammation. Because ART effectively controls HIV replication and stops its negative effect on the gut, researchers think that CMV may be a primary driver of the ongoing gut permeability and persistent systemic inflammation seen in people living with HIV on ART. CMV can also decrease the response to vaccines in people living with HIV. This is because the immune system is focused on fighting both HIV and CMV and doesn’t have the resources to properly respond to vaccines, as well as other pathogens.

Antiviral medications for CMV can decrease immune activation in people living with HIV, but older medications are not safe for long-term use. A new anti-CMV drug, letermovir, was approved in 2017 for transplant patients and is much safer than previous drugs.  CTNPT 047 is one of only two studies in the world that is testing this drug in people living with HIV. The study aims to understand how CMV affects people living with HIV and whether letermovir can reduce systemic inflammation and allow the damaged gut cells to repair.

Study Approach

This study is enrolling 60 patients living with HIV on ART. Forty patients will be randomized to receive letermovir once daily for 14 weeks, in addition to their regular ART regimen. Twenty participants will be randomized to continue taking ART only. Including the screening visit, there will be seven site visits over the course of the study where participants will have blood samples taken. Researchers will measure the levels of bacterial fragments (originating from the gut) in the blood and compare these levels between the letermovir and ART-only groups. They will also compare other markers of gut permeability, inflammation, and CMV-related immune response. There is also an optional substudy that participants can enroll in where colonoscopies and colon biopsies will be performed in two separate visits to directly assess changes in gut inflammation.