NCT02440789

Safety and Efficacy of Sirolimus for HIV Reservoir Reduction in Individuals on Suppressive Antiretroviral Therapy (ART)

Safety and Efficacy of Sirolimus for HIV Reservoir Reduction in Individuals on Suppressive Antiretroviral Therapy

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to find out about the safety of sirolimus in individuals with HIV infection who were also being treated with ART. The investigators wanted to learn whether sirolimus decreases inflammation and immune activation in the body; whether sirolimus changes the level of HIV in the participants' blood; and how sirolimus interacts with ART in the blood. Sirolimus is approved by the Food and Drug Administration (FDA) to prevent organ rejection in patients aged 13 years and older receiving kidney transplants. Sirolimus had also been used for the prevention of complications after stem cell transplants and as a treatment for certain kinds of cancers in HIV-infected patients.

Detailed description

The study was conducted with an initial lead-in period of 12 weeks where participants remained on ART, without study intervention. Samples were collected to define the pre-intervention steady-state of HIV, inflammation and immune activation parameters. At week 12, sirolimus therapy was initiated for the planned 20 weeks of treatment. In order to achieve therapeutic levels, sirolimus therapy was initiated with lead-in dose of 0.025 or 0.05 mg/kg/day, depending on the ART regimen. Doses for each participant were then adjusted, based on trough blood sirolimus concentrations, to achieve target concentrations between 5 and 10 ng/mL. There were frequent initial visits for sirolimus trough concentration monitoring and potential dose adjustments, at weeks 12.5, 13, 13.5, 14, 14.5, 15, 15.5 and 16. Then visits occurred at weeks 18, 20, 24, 28 and 32. After the week 32 visit, the planned end of study treatment, there was an additional 12 weeks of post-sirolimus follow-up, with a final visit at week 44. Study visits included physical examinations, clinical assessments, safety monitoring, and blood and oral swab collection. Anal swabs were collected at week 12 and 32. Samples were stored for subsequent protocol testing for the study outcomes. In the primary analysis, the significance level was 0.05 for all analyses.

Conditions

• HIV-1 Infection

Interventions

Type	Name	Description
DRUG	Sirolimus	Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.

Timeline

• Start date: 2015-12-21
• Primary completion: 2017-11-02
• Completion: 2018-02-01
• First posted: 2015-05-12
• Last updated: 2021-08-03
• Results posted: 2019-12-30

Locations

10 sites across 1 country: United States