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Perturbing of HIV Reservoir With Immune Stimulation

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by University of California, San Diego
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
David Smith, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT02707692
First received: February 23, 2016
Last updated: November 1, 2016
Last verified: November 2016
  Purpose
The purpose of this study is to determine the impact of Pneumococcus and Influenza vaccines on the HIV transcriptional activity in individuals who are virologically suppressed for at least 48 weeks on similar ART. The proposed study is a randomized double-blinded control trial conducted over 28 weeks. Randomized interventions will be injections of Influenza vaccine, Pneumococcal vaccine, and Placebo. Each participant will receive each injection but in a randomized order.

Condition Intervention
AIDS
HIV
Biological: Fluarix
Biological: Pneumovax
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Perturbing the HIV Reservoir With Immune Stimulation

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • CD4+ T cell-associated HIV RNA transcription [ Time Frame: Day 7 ]
    Average level of CD4+ T cell-associated HIV RNA transcription measured at day 7 after each injection.


Secondary Outcome Measures:
  • HIV DNA Levels [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of HIV DNA measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (IL-6) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: soluble IL-6 using commercial validated assays (ELISA) measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (TNF) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: soluble TNF using commercial validated assays (ELISA) measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (sCD14) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: soluble CD14 using commercial validated assays (ELISA) measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (sCD163) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: soluble CD163 (sCD163) using commercial validated assays (ELISA) measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (CD3) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: cellular marker CD3 measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (CD4) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: cellular marker CD4 measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (CD8) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: cellular marker CD8 measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (CD38) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: cellular marker CD38 measured at 2, 4, 7, 14, 30 days after each injection

  • Immune Activation (DR) [ Time Frame: Days 2, 4, 7, 14, 30 ]
    Levels of Immune Activation: cellular marker DR measured at 2, 4, 7, 14, 30 days after each injection

  • Selective HIV RNA Production [ Time Frame: 30 days post vaccination ]
    Determine selective HIV RNA production from HIV DNA (by next generation sequencing and panmixia tests) among the five participants with the highest levels of cell associated HIV RNA following active vaccination.

  • Nonselective HIV RNA Production [ Time Frame: 30 days post vaccination ]
    Determine nonselective HIV RNA production from HIV DNA (by next generation sequencing and panmixia tests) among the five participants with the highest levels of cell associated HIV RNA following active vaccination.

  • Levels of replication competent HIV DNA [ Time Frame: 30 days post vaccination ]
    Levels of replication competent HIV DNA (by quantitative viral outgrowth assays) among the five participants with the highest levels of cell associated HIV RNA following active vaccination.

  • Levels of HIV specific immune response [ Time Frame: 30 days post vaccinations ]
    Levels of HIV specific immune response 30 days after each injection.

  • Stimulation of HIV transcription (incidental illness) [ Time Frame: 30 days post vaccinations ]
    Measure stimulation of HIV transcription by incidental illness over the course of the study.

  • Stimulation of HIV transcription (human herpesvirus replication) [ Time Frame: 30 days post vaccinations ]
    Measure stimulation of HIV transcription by human herpesviruses replication over the course of the study.

  • Stimulation of HIV transcription (microbial translocation) [ Time Frame: 30 days post vaccinations ]
    Measure stimulation of HIV transcription by microbial translocation over the course of the study.


Estimated Enrollment: 56
Study Start Date: August 2016
Estimated Study Completion Date: January 2021
Estimated Primary Completion Date: January 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo, Flu, Pneumovax

Each subject will take Influenza (Fluarix®, GSK), Pneumococcal (Pneumovax®23, Merck), and placebo. Randomization will determine the order in which the subjects receive the injections. There are six potential study arms, one for each order in which someone could receive the injections:

Arm 1: Placebo, Flu, Pneumovax

Biological: Fluarix
Intramuscular injection with Fluarix® .
Biological: Pneumovax
Intramuscular injection with Pneumovax.
Other: Placebo
Intramuscular injection with sterile saline (placebo).
Arm 2: Placebo, Pneumovax, Flu
Arm 2: Placebo, Pneumovax, Flu
Biological: Fluarix
Intramuscular injection with Fluarix® .
Biological: Pneumovax
Intramuscular injection with Pneumovax.
Other: Placebo
Intramuscular injection with sterile saline (placebo).
Arm 3: Flu, Placebo, Pneumovax
Arm 3: Flu, Placebo, Pneumovax
Biological: Fluarix
Intramuscular injection with Fluarix® .
Biological: Pneumovax
Intramuscular injection with Pneumovax.
Other: Placebo
Intramuscular injection with sterile saline (placebo).
Arm 4: Pneumovax, Placebo, Flu
Arm 4: Pneumovax, Placebo, Flu
Biological: Fluarix
Intramuscular injection with Fluarix® .
Biological: Pneumovax
Intramuscular injection with Pneumovax.
Other: Placebo
Intramuscular injection with sterile saline (placebo).
Arm 5: Pneumovax, Flu, Placebo
Arm 5: Pneumovax, Flu, Placebo
Biological: Fluarix
Intramuscular injection with Fluarix® .
Biological: Pneumovax
Intramuscular injection with Pneumovax.
Other: Placebo
Intramuscular injection with sterile saline (placebo).
Arm 6: Flu, Pneumovax, Placebo
Arm 6: Flu, Pneumovax, Placebo
Biological: Fluarix
Intramuscular injection with Fluarix® .
Biological: Pneumovax
Intramuscular injection with Pneumovax.
Other: Placebo
Intramuscular injection with sterile saline (placebo).

Detailed Description:

Title: Perturbing the HIV Reservoir

Sample Size: 56

Study Population: HIV-infected individuals between 18 and 50 years old who started similar antiretroviral therapy (ART) during chronic infection and remained virally suppressed for at least 48 weeks before enrollment. Participants will have CD4 >350 cells/μl at enrollment and a CD4 nadir >200 cells/μl.

Participating Sites: UCSD's Antiviral Research Center (AVRC)

Study Design: The proposed study is a randomized double-blinded control trial conducted over 28 weeks. Randomized interventions will be injections of Influenza vaccine, Pneumococcal vaccine, and Placebo. Each participant will receive each injection but in a randomized order.

Schedule of Evaluations: Study evaluations will be based on three 30 day cycles (Influenza vaccine, Pneumococcus vaccine, Placebo in random order) over 28 weeks of the RCT. Pre injection: one paired blood and genital secretion sample will be collected before each injection. Post-injection: paired blood and genital secretion samples will be collected on days 2, 4, 7, 14 and 30 after each injection.

Study Duration: 240 weeks

Study Regimen/Intervention: This is a double blind RCT of two vaccines (Pneumovax®23 and Fluarix®) plus placebo (sterile saline injection). Study participants will be followed for 28 weeks after enrollment. During this 28-week period, blood and genital secretion samples will be collected on day 0 and five subsequent time points after each injection (days 2, 4, 7, 14 and 30). Injections (vaccine or placebo) will be administered 12 weeks apart and in a random order, to minimize a possible bias due to the order of the vaccines.

Primary Objective: To determine the impact of Pneumococcus and Influenza vaccines on the HIV transcriptional activity in individuals who are virologically suppressed for at least 48 weeks on similar ART.

Primary Outcome: Average level of CD4+ T cell-associated HIV RNA transcription measured at days 2, 4, 7, 14 and 30 after each injection.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented HIV-1 infection (HIV antibody or viral load positive).
  • Capable of signing written informed consent.
  • Men and women between 18 and 50 years of age.
  • Read and comprehend English.
  • CD4 count at enrollment >350 cells/ml and nadir >200 cells/ml.
  • Recent vaccination history (previous year flu vaccination and pneumovax at least 4 weeks prior to screening visit) and antibody levels consistent with previous vaccination with both influenza and pneumococcus.
  • Must be on non-nucleoside reverse transcriptase or integrate inhibitor base ART.

Exclusion Criteria:

  • Uncontrolled psychiatric condition.
  • Under the influence of drug(s) or alcohol at time of screening.
  • Any condition that, in the opinion of the investigator, would limit follow-up and adequate consent.
  • History of allergic reactions to any of the proposed vaccines or egg allergy.
  • History of Gullian Barre syndrome.
  • Receiving immunosuppressive medications.
  • Pregnancy or lactation.
  • Receiving an ART regiment that contains a protease inhibitor
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02707692

Contacts
Contact: Jill Kunkel, RN 619-543-3094 jkunkel@ucsd.edu
Contact: Pieter Baker, MPH 619-543-2759 pabaker@ucsd.edu

Locations
United States, California
UCSD Antiviral Research Center (AVRC) Recruiting
San Diego, California, United States, 92103-8208
Contact: Jill Kunkel, RN    619-543-3094    jkunkel@ucsd.edu   
Contact: Pieter Baker, MPH    619-543-2759    pabaker@ucsd.edu   
Principal Investigator: David Smith, MD         
Sub-Investigator: Susan Little, MD         
Sub-Investigator: Sara Gianella, MD         
Sponsors and Collaborators
University of California, San Diego
National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Responsible Party: David Smith, Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02707692     History of Changes
Other Study ID Numbers: 160089
1R01AI118422-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: February 23, 2016
Last Updated: November 1, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University of California, San Diego:
HIV
AIDS
Immune Stimulation
HIV Reservoir

Additional relevant MeSH terms:
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017