Impact of influenza and pneumococcal vaccines on inflammatory response during suppressive antiretroviral therapy

OBJECTIVE: We performed a secondary analysis of a randomized clinical trial that evaluated stimulation of HIV reservoir through routine vaccines (NCT02707692) to characterize vaccine-induced inflammatory responses and their association with HIV virologic measures following influenza and pneumococcal vaccination in people with HIV (PWH) on suppressive antiretroviral therapy (ART). DESIGN: Prospective, randomized, double-blinded, placebo-controlled, crossover trial evaluating influenza and pneumococcal vaccines. METHODS: Fifty-four PWH on ART were enrolled. Blood was collected at baseline and days 2, 4, 7, 14, and 30 postvaccination. Of 41 cytokines quantified by Luminex, 19 with >30% detectable values postbaseline were analyzed. Cellular HIV RNA and DNA were measured by ddPCR. Analyses included partial least squares discriminant analysis (PLSDA) and linear mixed-effects models. RESULTS: Fifty-three participants contributed ≥1 postvaccination visit. We observed no distinct cytokine profile by vaccine type or placebo. Pneumococcal vaccination induced transient increases in LBP [0.231; 95% confidence interval (CI): [0.126, 0.336]; P = 0.0003) and C-reactive protein (0.643; 95% CI: [0.482, 0.804]; P < 0.0001), while influenza vaccination was associated with a modest decrease in RANTES (-0.116; 95% CI: [-0.188, -0.043]; P = 0.0218) compared with placebo. Independent of vaccine type, HIV DNA Gag levels were inversely associated with interleukin (IL)-16 and RANTES. CONCLUSIONS: In PWH on suppressive ART, influenza and pneumococcal vaccination elicited mild and transient changes in individual cytokines, though distinct global cytokine signatures were not observed. This finding supports vaccine safety in PWH, showing no broad inflammatory perturbations. Independent of vaccine type, specific cytokines (IL-16 and RANTES) were associated with HIV reservoir measures, suggesting potential roles in reservoir dynamics and immune activation.