Attenuation of HIV-Specific T Cell Responses Among People with HIV on art Following Dipyridamole Treatment

Twelve weeks of dipyridamole increased extracellular adenosine levels and decreased T cell activation in people with human immunodeficiency virus (HIV). In this analysis, we investigated the effect of dipyridamole on HIV-specific T cell responses. We compared changes in Gag- and Env-specific T cell responses using intracellular cytokine staining, following 12 wk of dipyridamole treatment vs placebo. We evaluated whether frequencies of polyfunctional HIV-specific T cells were associated with purines in the adenosine pathway and with measures of HIV persistence and chronic inflammation. There was a significant decrease in CD4+ polyfunctional T cell responses to Gag (-62.6% vs -23.0%; P < 0.001) and Env (-56.1% vs -6.0%; P < 0.001) in the dipyridamole arm. In the dipyridamole group, lower frequencies of polyfunctional Env-specific CD4+ T cells were associated with higher plasma levels of adenosine (r = -0.85, P < 0.01) and inosine (r = -0.70, P = 0.04). Higher adenosine levels induced by dipyridamole treatment is associated with decreased HIV-specific CD4+ T cell polyfunctional responses in people with HIV on antiretroviral therapy.