Reducing Proviral HIV DNA With Interferon-a
- Conditions
- HIVHIV/AIDS
- Interventions
- Drug: Peg-IFN-α2b
- Registration Number
- NCT02227277
- Lead Sponsor
- The Wistar Institute
- Brief Summary
The purpose of this study is to determine if treatment with pegylated interferon alpha 2b (peg-IFN-α2b) will reduce the amount of integrated HIV DNA in peripheral blood cells and tissues of individuals with chronic HIV infection receiving antiretroviral treatment (ART).
A reduction and/or clearance of the latent viral reservoir (i.e.: virus that remains dormant in HIV-infected subjects receiving suppressive treatment ) is considered essential for HIV eradication.
By measuring the changes in integrated proviral HIV DNA, which is considered a surrogate measure of the latent reservoir, the investigators will establish if peg-IFN-α2b treatment should be considered as a component of future viral eradication strategies.
- Detailed Description
Our long-term goal is to evaluate the effect of pegylated interferon (peg-IFN) α as an anti-HIV reservoir immunotherapy that could potentiate eradication strategies against HIV.
The present study is a 3-arm randomized clinical trial (RCT). The aim of this study is to determine whether a 20-week treatment course with 1μg/kg/week of pegylated interferon alpha 2 b (peg-IFN-α2b) will reduce the levels of HIV-1 proviral DNA levels in circulating PBMC and mucosa-associated lymphoid tissue (MALT) in HIV-infected individuals receiving long-term ART.
In addition, we will study if a 4-week interruption of ART is necessary to observe any change in proviral DNA levels.
In our previous study (NCT00594880) with a different form of Interferon alpha (peg-IFN-α2a), we observed a reduction in proviral DNA in peripheral blood cells in 50% of the patients. However, we did not measure the levels in MALT, and we could not determine whether or not an interruption of ART was necessary. The present study will address these questions.
We will also seek to determine the biological mechanisms (such as an increase in Natural Killer cell cytotoxicity) that mediate the antiviral effects of peg-IFN-α.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 54
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Conditional 12-week ART interruption Peg-IFN-α2b 18 participants will receive peg-IFN-α2b (1 μg/kg/week) for 20 weeks. Continuous ART Peg-IFN-α2b 18 participants will receive peg-IFN-α2b (1 μg/kg/week) for 20 weeks.
- Primary Outcome Measures
Name Time Method Integrated HIV proviral DNA 24 weeks The study endpoint is the change in the number of copies of integrated HIV DNA/10\^6 CD4+ T cells (as assessed by Alu-HIV gag PCR) between baseline and 20 weeks of peg-IFNα-2b administration (study week 24).
- Secondary Outcome Measures
Name Time Method Integrated proviral DNA in tissue 24 weeks Copies of HIV DNA per tissue derived 2x106 isolated lymphocytes (GALT biopsy)-recovered lymphocyte (week 0 vs. week 24)
CD4 count 24 weeks compare the frequency of occurrence of CD4 count \< 350 (trigger to resume ART during ART interruption in arm 1) between study arms
Viral load 24 weeks compare the frequency of occurrence of VL \> 50 copies/ml (trigger for resuming ART during ART interruption in arm 1) between arms
Trial Locations
- Locations (3)
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Jonathan Lax Center at Philadelphia FIGHT
🇺🇸Philadelphia, Pennsylvania, United States
Penn-Presbyterian Hospital
🇺🇸Philadelphia, Pennsylvania, United States