Impact of influenza and pneumococcal vaccines on HIV persistence and immune dynamics during suppressive antiretroviral therapy

Abstract

Objective: We sought to determine if standard influenza and pneumococcal vaccines can be used to stimulate HIV reservoirs during antiretroviral therapy (ART).

Design: A prospective, randomized, double-blinded, placebo-controlled, crossover trial of two clinically recommended vaccines (influenza and pneumococcal).

Methods: Persons with HIV on ART ( N = 54) were enrolled in the clinical trial. Blood was collected at baseline and days 2,4,7,14, and 30 postimmunizations. Levels of cellular HIV RNA and HIV DNA were measured by ddPCR. Expression of immunological markers on T cell subsets was measured by flow cytometry. Changes in unspliced cellular HIV RNA from baseline to day 7 postinjection between each vaccine and placebo was the primary outcome.

Results: Forty-seven participants completed at least one cycle and there were no serious adverse events related to the intervention. We observed no significant differences in the change in cellular HIV RNA after either vaccine compared with placebo at any timepoint. In secondary analyses, we observed a transient increase in total HIV DNA levels after influenza vaccine, as well as increased T cell activation and exhaustion on CD4 + T cells after pneumococcal vaccine.

Conclusion: Clinically recommended vaccines were well tolerated but did not appear to stimulate the immune system strongly enough to elicit significantly noticeable HIV RNA transcription during ART.Clinicaltrials.gov identifier: NCT02707692.

Figure 1.. Study Design Figure

Randomized, double blinded, crossover study design to administer pneumococcal vaccine (Pneumovax-23^®), influenza vaccine (Fluarix^®), and placebo vaccine (saline) to participants, who were scheduled to attend one vaccination visit during each of 3 cycles followed by 5 visits at 2, 4, 7, 14, and 30 days after vaccination for collection of blood and optional genital secretion. The washout period between cycles was at least 6 weeks long.

Figure 2.. Distribution of cellular HIV RNA (Primary Analysis) and Total HIV DNA Outcomes by Vaccine or Placebo Injection at Day 7.

Change in levels of cellular unspliced HIV RNA_Gag, spliced HIV RNA_TatRev, total HIV DNA, and HIV DNA 2-LTR (normalized for one million cells and log transformed) from day of vaccination to seven days later by vaccine and placebo administration. Outliers are indicated with arrows.