Respiratory viral (RV) infections represent a major threat for human health worldwide. Persons with HIV (PWH) have a compromised immune response and are thought to be at higher risk for severe RV disease. However, very little is known about the host immune response to RV infection in PWH. Here, we investigated gene expression changes in the peripheral blood of PWH co-infected with RV. Only very few differentially expressed genes could be detected between PWH with and without RV infection, suggesting that the immune response to RV in PWH is strongly dampened. Our data provides important insights into the host response to RV infections in HIV patients.