Interferon Alpha 2b Intensification in HIV-Positive Individuals on Antiretroviral Therapy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01295515|
Recruitment Status : Completed
First Posted : February 14, 2011
Results First Posted : April 23, 2019
Last Update Posted : April 23, 2019
- Antiretroviral therapy (ART) has been able to improve the lifespan of individuals infected with human immunodeficiency virus type 1 (HIV-1), but ART requires continuous treatment that has substantial consequences on quality of life. Recent research is attempting to determine whether this persistent infection stems from a low-level infection where new cells are continually infected with HIV, or from cells that live for a long time after infection. ART is very active against the virus in new cells, but has no effect on long-lived cells that are already infected with HIV-1 at the start of ART. As a result, new strategies may be necessary to reduce or eradicate these 'reservoir' cells.
- Interferon is a natural substance made by the body to combat virus infections, and can be made as an injectable drug known as PEGINTRON. Researchers are interested in determining whether PEGINTRON therapy will also reduce the residual low levels of HIV in patients who are already taking ART.
- To evaluate the effectiveness of PEGINTRON injections on HIV levels in participants currently undergoing antiretroviral therapy.
- Individuals at least 18 years of age who have been diagnosed with HIV, are currently undergoing antiretroviral therapy, and have maintained HIV virus blood counts that are not detectable by current commercial tests for at least 12 months before the start of the study.
- This study will involve separate screening and treatment processes.
- Participants will be screened with a physical examination and medical history, including blood and urine samples. The screening analysis to determine study eligibility will take several weeks. Participants will have apheresis to provide sufficient numbers of blood cells for evaluation by the study researchers.
- Eligible participants will begin a 4-week course of PEGINTRON injections using the standard dose of PEGINTRON that is approved for treatment of chronic hepatitis C. Participants will have weekly injections and have frequent blood tests to measure HIV virus levels.
- Participants who experience problems in maintaining safe numbers of white blood cells during the study may receive injections of filgrastim to increase their white blood cell count.
- After the 4 weeks of treatment, participants will return for additional blood tests on study days 28, 35, 42, 49, 56, and 84, and Weeks 16, 24, 36, and 48 (i.e., through the end of 1 year after the start of the study).
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection||Drug: Pegylated Interferon Alpha 2b (PEGINTRON)||Phase 1 Phase 2|
As a result of combination antiretroviral therapy (ART), morbidity and mortality from acquired immunodeficiency syndrome has declined significantly in the past 15 years, at least in developed countries. Human immunodeficiency virus type 1 (HIV-1) infected individuals now live longer, but must undergo continuous therapy that has substantial consequences on quality of life.
ART suppresses HIV-1 viremia below the limits of detection in current commercial assays (c. 50 copies/mL plasma), but HIV viremia persists even after prolonged suppressive therapy. The origin of this residual viremia is yet not clear, but data suggest that production from long lived HIV infected cells may contribute to viremia.
Antiretrovirals are extremely active against replicating cells, and can thus successfully stop viral replication, but have no effect on long-lived viral reservoirs of cells already infected with HIV-1 at the time antiretroviral therapy is initiated. As a result, new strategies are necessary to reduce or eradicate long-lived reservoirs.
Interferon alpha is a natural cytokine with antiviral activity. Prior to the introduction of antiretroviral therapy, several studies demonstrated modest effect of interferon alpha in HIV-1 viremia in active cycles of infection in infected individuals. Interferon alpha was also effective in vitro in decreasing virus production from cells chronically infected with HIV-1. With the introduction of potent antiretroviral therapy, interferon was not developed as a direct anti-HIV drug. Interferon alpha is relatively effective in therapy of hepatitis C virus (HCV) infection, and has been used in HIV-1/HCV coinfected individuals. Kottilil and coworkers in the Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases (NIAID) have shown a decrease in HIV-1 ribonucleic acid (RNA) levels in HCV coinfected participants treated with pegylated interferon alpha and ribavirin. In stored samples from that study, we conducted a retrospective trial on samples from participants with HIV-1 RNA levels of <50 copies/mL, showing a further reduction in residual viremia using an ultrasensitive Single Copy Assay (SCA) developed in our laboratory. As such the effects of interferon on HIV viremia and cell associated HIV RNA are of growing interest.
In this protocol we will conduct a prospective, non-randomized, single arm, pilot study to investigate the effect of pegylated interferon alpha 2b on HIV-1 RNA levels as an additional drug in participants undergoing suppressive antiretroviral therapy with viral RNA levels suppressed to less than 50 copies/mL plasma. As patients may have levels of HIV RNA that are lower than our limit of detection, we will also investigate levels of HIV nucleic acid species in cells as well. We will determine whether interferon alpha therapy will reduce residual viremia or cell associated HIV RNA in participants on suppressive ART, which will expand our understanding of persistent low-level viremia and the pathogenesis of HIV in infected individuals.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effect of Interferon Alpha 2b Intensification on HIV-1 Residual Viremia in Individuals Suppressed on Antiretroviral Therapy|
|Actual Study Start Date :||February 11, 2011|
|Actual Primary Completion Date :||May 31, 2017|
|Actual Study Completion Date :||May 31, 2017|
Experimental: Interferon treatment
Interferon treatment The intervention is administration of Pegylated Interferon Alpha 2b (PEGINTRON) weekly for four weeks
Drug: Pegylated Interferon Alpha 2b (PEGINTRON)
pegylated preparation of interferon alpha 2b
Other Name: PEGINTRON
- Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) [ Time Frame: week 4 (post) compared to week 0 (pre) ]Cell associated HIV nucleic acid levels were measured using a single copy assay, and numbers of cells were quantified using a polymerase chain reaction method that detects RNA.
- Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Deoxyribonucleic Acid (DNA) [ Time Frame: week 4 (post) compared to week 0 (pre) ]Cell associated HIV nucleic acid levels were measured using a single copy assay, and numbers of cells were quantified using a polymerase chain reaction method that detects C-C chemokine receptor type 5 (CCR5) DNA.
- Fold Change in Ribonucleic Acid (RNA) and Deoxyribonucleic Acid (DNA) in Human Immunodeficiency Virus Type 1 (HIV-1) Genetic Variation in Individuals Undergoing Interferon Therapy [ Time Frame: week 4 (post) and week 0 (pre) ]The outcome measure is the fold change in the ratio of HIV RNA to HIV DNA. For the pre and post interferon time point, the level of HIV RNA is divided by the level of HIV DNA and this ratio of the HIV RNA/DNA pre and post interferon is calculated to yield the fold change in HIV RNA/DNA levels. Fold change does not have units.
- Pre-and Post- Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) in HIV-infected Individuals [ Time Frame: week 4 (post) compared to week 0 (pre) ]The outcome measure is copies of HIV RNA per ml of plasma. HIV RNA levels are measured using a polymerase chain reaction method.
- Count of Participants With Serious and Non-serious Adverse Events Assessed by the Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading Adult Adverse Events. [ Time Frame: Date consent signed to date off study, approximately 66 months and 2 days. ]Here is the count of participants with serious and non-serious adverse events assessed by the Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading Adult Adverse Events for severity (mild/moderate/severe), expectedness (expected/unexpected), and relatedness to study drug (definitely, probably, possibly, unlikely, or unrelated).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01295515
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15261|
|Principal Investigator:||Frank Maldarelli, M.D.||National Cancer Institute (NCI)|