Perturbing of HIV Reservoir With Immune Stimulation

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.

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.