AIDS 392: TRAILBLAZER, elimination of CCR5 receptors with zinc finger to prevent viral replication


Title:

AIDS 392: TRAILBLAZER, elimination of CCR5 receptors with zinc finger to prevent viral replication, in participants living with HIV

Purpose:

The main purpose of this study is to test a new type of strategy to treat HIV: giving people living with HIV genetically modified versions of their own CD4+ T-cells that are resistant to HIV infection.

There have been a few other trials looking at this strategy, but more trials will be necessary before we know whether this strategy actually works. Participants will continue taking their anti-HIV medicines during the study.

Trailblazer is divided into two phases. Phase I involves collecting and modifying the participant’s CD4+ T-cells, collected through a process called leukapheresis. The CD4+ T-cells are then genetically modified so they are basically immune to HIV infection by disabling a coreceptor called CCR5 necessary for HIV to infect the cell. Following the modification, the CD4+ T-cells are grown to increase their numbers. Phase II of the trial is where participants are given two infusions, one of cyclophosphamide and three days later an infusion of their CD4+ T-cells. Participants return to the clinic for an additional 16 visits over the next two years.

The study will see whether the strategy is working by measuring the effect it has on the size of the participant’s HIV reservoir (those cells in a person that are infected with HIV but are not actively making new copies). We call these cells ‘resting’ or ‘latent’. Anti-HIV medicines do not have any effect on these resting cells. These cells are the reason why HIV comes back after someone stops taking their anti-HIV medicines.

Requirements to Enter study:

Below are some of the requirements to join Trailblazer. A Clinical Trials Site staff member can explain other requirements to join the study.:

  • HIV-positive adults, ages 18-70.
  • Adults born female with childbearing potential may not join the study. Adults born male must be willing to abstain from sexual intercourse than can result in pregnancy for a 90-day period during the trial.
  • CD4+ T-cell count greater than 350.
  • On stable anti-HIV medicine regimen (ARVs) with an HIV viral load less than 50 (undetectable) for at least 48 weeks (certain viral blips OK) with no planned changes in ARVs for duration of trial;
  • No prior gene therapy using an integrating vector;
  • No prior use (within 4 weeks of screening) of maraviroc or any CCR5 inhibitor.
  • No acute or chronic hepatitis C or hepatitis B. People cured of hepatitis C may join.
  • No prior AIDS-defining condition within the last 5 years (other than CD4+ T-cell count less than 200).
  • No active cancer or malignancy within 5 years.

Duration of Study:

Participants will be in this study for about 27 months.

Compensation Provided

NIH study page: https://clinicaltrials.gov/ct2/show/NCT03666871