AIDS, HIV
Conditions
Keywords
HIV, AIDS, Immune Stimulation, HIV Reservoir
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.
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.
Interventions
BIOLOGICALFluarix
Intramuscular injection with Fluarix® .
BIOLOGICALPneumovax
Intramuscular injection with Pneumovax.
OTHERPlacebo
Intramuscular injection with sterile saline (placebo).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Vaccination (Day 0) in Mean CD4+ T Cell-associated HIV RNA Transcription at Day 7 | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment dates: 2016 to 2020 Recruitment location: Conducted in HIV clinics and at clinical trial site, UC San Diego AntiViral Research Center in San Diego, CA
Pre-assignment details
Participants had a wash out period of no less than 4 weeks between vaccination series. Participants were excluded from the study before randomization and study assignments if their HIV viral loads were detectable from blood samples collected at screening.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 9 |
| 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). | 9 |
| 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). | 9 |
| 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®). | 9 |
| 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). | 9 |
| 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®). | 9 |
| Total | 54 |
Baseline characteristics
| Characteristic | Pneumococcal, Then Placebo, Then Influenza Vaccination | Influenza, Then Pneumococcal, Then Placebo Vaccination | Influenza, Then Placebo, Then Pneumococcal Vaccination | Placebo, Then Pneumococcal, Then Influenza Vaccination | Placebo, Then Influenza, Then Pneumococcal Vaccination | Total | Pneumococcal, Then Influenza, Then Placebo Vaccination |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.9 years STANDARD_DEVIATION 9.5 | 42.2 years STANDARD_DEVIATION 13.4 | 44.3 years STANDARD_DEVIATION 10.2 | 46.9 years STANDARD_DEVIATION 10.1 | 48.0 years STANDARD_DEVIATION 10.9 | 45.0 years STANDARD_DEVIATION 11 | 45.8 years STANDARD_DEVIATION 13.4 |
| CD4 Counts | 814.9 cells/microliters STANDARD_DEVIATION 267.9 | 798.4 cells/microliters STANDARD_DEVIATION 280 | 724.4 cells/microliters STANDARD_DEVIATION 256.7 | 753.8 cells/microliters STANDARD_DEVIATION 242.4 | 639.9 cells/microliters STANDARD_DEVIATION 222.1 | 752.8 cells/microliters STANDARD_DEVIATION 248.6 | 785.4 cells/microliters STANDARD_DEVIATION 248.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 4 Participants | 5 Participants | 4 Participants | 27 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 5 Participants | 4 Participants | 5 Participants | 27 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 8 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants | 6 Participants | 9 Participants | 5 Participants | 42 Participants | 8 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 9 participants | 9 participants | 9 participants | 54 participants | 9 participants |
| Sex/Gender, Customized Gender Female | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants | 3 Participants |
| Sex/Gender, Customized Gender Male | 8 Participants | 8 Participants | 8 Participants | 7 Participants | 8 Participants | 45 Participants | 6 Participants |
| Sex/Gender, Customized Gender Trans or non-binary | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants |
| Virologically suppressed Suppressed (< 50 copies/ml) | 9 Participants | 9 Participants | 9 Participants | 8 Participants | 8 Participants | 52 Participants | 9 Participants |
| Virologically suppressed Unknown | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Virologically suppressed Viremic (>= 50 copies/ml) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 45 | 0 / 48 |
| other Total, other adverse events | 0 / 45 | 0 / 45 | 0 / 48 |
| serious Total, serious adverse events | 1 / 45 | 0 / 45 | 0 / 48 |
Outcome results
Primary
Change From Vaccination (Day 0) in Mean CD4+ T Cell-associated HIV RNA Transcription at 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.
Time frame: Day 0 and Day 7
Population: Within each cycle, all participants who received the vaccination and completed the Day-7 visit were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pneumococcal Vaccine | Change From Vaccination (Day 0) in Mean CD4+ T Cell-associated HIV RNA Transcription at Day 7 | -471.8 HIV RNA copies per million cell | Standard Deviation 2998 |
| Influenza Vaccine | Change From Vaccination (Day 0) in Mean CD4+ T Cell-associated HIV RNA Transcription at Day 7 | -45.9 HIV RNA copies per million cell | Standard Deviation 243.2 |
| Placebo | Change From Vaccination (Day 0) in Mean CD4+ T Cell-associated HIV RNA Transcription at Day 7 | 332.3 HIV RNA copies per million cell | Standard Deviation 2266.4 |
Comparison: Primary hypothesis: Participants will have a higher absolute difference in levels of CD4+ T cell-associated HIV RNA transcription seven days after receiving either Pneumococcal or Influenza vaccinations, when compared to seven days after receiving placebo.p-value: 0.3295% CI: [-2996.3, 1020.3]Paired t-test, 2 sided
Comparison: Primary hypothesis: Participants will have a higher absolute difference in levels of CD4+ T cell-associated HIV RNA transcription seven days after receiving either Pneumococcal or Influenza vaccinations, when compared to seven days after receiving placebo.p-value: 0.3195% CI: [-1199.7, 389.7]Paired t-test, 2 sided