Perturbing of HIV Reservoir With Immune Stimulation

• ClinicalTrials.gov Identifier: NCT02707692
• Recruitment Status: Completed
• First Posted: March 14, 2016
• Results First Posted: August 24, 2022
• Last Update Posted: August 24, 2022
• Sponsor: University of California, San Diego
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): David Smith, University of California, San Diego

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
AIDS; HIV	Biological: Fluarix; Biological: Pneumovax; Other: Placebo	Not Applicable

Detailed Description:

Title: Perturbing the HIV Reservoir

Sample Size: 56

Study Population: HIV-infected individuals between 18 and 65 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 >250 cells/μl at enrollment and a CD4 nadir >100 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Perturbing the HIV Reservoir With Immune Stimulation
• Actual Study Start Date: August 2016
• Actual Primary Completion Date: April 2020
• Actual Study Completion Date: January 2022

Arms and Interventions

Arm	Intervention/treatment
Pneumococcal, then Influenza, then Placebo vaccination; Participants first received a 0.5 mL injection of Pneumococcal vaccine (Pneumovax-23®). After a washout period of at least 6 weeks, they then received a 0.5 mL injection of Influenza vaccine (Fluarix®, GSK). After another washout period of at least 6 weeks, the participant received a 0.5 mL injection of saline (placebo).	Biological: Fluarix; Intramuscular injection with Fluarix® .; Biological: Pneumovax; Intramuscular injection with Pneumovax.; Other: Placebo; Intramuscular injection with sterile saline (placebo).
Pneumococcal, then Placebo, then Influenza vaccination; Participants first received a 0.5 mL injection of Pneumococcal vaccine (Pneumovax-23®). After a washout period of at least 6 weeks, they then received a 0.5 mL injection of saline (placebo). After another washout period of at least 6 weeks, the participant received a 0.5 mL injection of Influenza vaccine (Fluarix®, GSK).	Biological: Fluarix; Intramuscular injection with Fluarix® .; Biological: Pneumovax; Intramuscular injection with Pneumovax.; Other: Placebo; Intramuscular injection with sterile saline (placebo).
Influenza, then Pneumococcal, then Placebo vaccination; Participants first received a 0.5 mL injection of Influenza vaccine (Fluarix®, GSK). After a washout period of at least 6 weeks, they then received a 0.5 mL injection of Pneumococcal vaccine (Pneumovax-23®). After another washout period of at least 6 weeks, the participant received a 0.5 mL injection of saline (placebo).	Biological: Fluarix; Intramuscular injection with Fluarix® .; Biological: Pneumovax; Intramuscular injection with Pneumovax.; Other: Placebo; Intramuscular injection with sterile saline (placebo).
Influenza, then Placebo, then Pneumococcal vaccination; Participants first received a 0.5 mL injection of Influenza vaccine (Fluarix®, GSK). After a washout period of at least 6 weeks, they then received a 0.5 mL injection of saline (placebo). After another washout period of at least 6 weeks, the participant received a 0.5 mL injection of Pneumococcal vaccine (Pneumovax-23®).	Biological: Fluarix; Intramuscular injection with Fluarix® .; Biological: Pneumovax; Intramuscular injection with Pneumovax.; Other: Placebo; Intramuscular injection with sterile saline (placebo).
Placebo, then Pneumococcal, then Influenza vaccination; Participants first received a 0.5 mL injection of saline (placebo). After a washout period of at least 6 weeks, they then received a 0.5 mL injection of Pneumococcal vaccine (Pneumovax-23®). After another washout period of at least 6 weeks, the participant received a 0.5 mL injection of Influenza vaccine (Fluarix®, GSK).	Biological: Fluarix; Intramuscular injection with Fluarix® .; Biological: Pneumovax; Intramuscular injection with Pneumovax.; Other: Placebo; Intramuscular injection with sterile saline (placebo).
Placebo, then Influenza, then Pneumococcal vaccination; Participants first received a 0.5 mL injection of saline (placebo). After a washout period of at least 6 weeks, they then received a 0.5 mL injection of Influenza vaccine (Fluarix®, GSK). After another washout period of at least 6 weeks, the participant received a 0.5 mL injection of Pneumococcal vaccine (Pneumovax-23®).	Biological: Fluarix; Intramuscular injection with Fluarix® .; Biological: Pneumovax; Intramuscular injection with Pneumovax.; Other: Placebo; Intramuscular injection with sterile saline (placebo).

Outcome Measures

Primary Outcome Measures :

1. Change From Vaccination (Day 0) in Mean CD4+ T Cell-associated HIV RNA Transcription at Day 7 [ Time Frame: Day 0 and Day 7 ]
   CD4+ T cell-associated HIV RNA was measured before vaccination on Day 0 and again on Day 7. The Day-0 measure of CD4+ T cell-associated HIV RNA transcription was subtracted from the Day-7 measure.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

1. Documented HIV-1 infection more than 365 days ago (HIV antibody or viral load positive).
2. Capable of signing written informed consent.
3. Documented viral s suppression for at least 48 weeks (≤50 copies/mL)
4. Men and women between 18 and 65 years of age.
5. Read and comprehend English.
6. Documented CD4 count at enrollment (>250 cells/µl)
7. Reported CD4 nadir >100 cells/µl.
8. Received seasonal flu vaccination at least 6 weeks prior to first trial injection (and not more recently)
9. Received vaccination for pneumococcal disease at least 12 months prior to first trial injection (and not more recently)
10. Started ART during chronic infection (> 6 months from estimated date of injection)

Exclusion Criteria

1. Uncontrolled psychiatric condition.
2. Under the influence of drug(s) or alcohol at time of screening.
3. Any condition that, in the opinion of the investigator, would limit follow-up and adequate consent.
4. History of allergic reactions to any of the proposed vaccines or egg allergy.
5. History of Gullian Barre syndrome
6. Receiving immunosuppressive medications.
7. Pregnancy or lactation.

Contacts and Locations

Locations

United States, California

UCSD Antiviral Research Center (AVRC)

San Diego, California, United States, 92103-8208

Sponsors and Collaborators

University of California, San Diego

National Institute of Allergy and Infectious Diseases (NIAID)

  Study Documents (Full-Text)

Documents provided by David Smith, University of California, San Diego:

Study Protocol and Statistical Analysis Plan  [PDF] March 15, 2018

More Information

• Responsible Party: David Smith, Professor of Medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT02707692
• Other Study ID Numbers: 160089; 1R01AI118422-01A1 ( U.S. NIH Grant/Contract )
• First Posted: March 14, 2016
• Results First Posted: August 24, 2022
• Last Update Posted: August 24, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by David Smith, 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