Type I interferon production is profoundly and transiently impaired in primary HIV-1 infection

Background. Successful immunological control of human immunodeficiency virus (HIV) infection is achieved only in rare individuals. Plasmacytoid dendritic cells (DCs) are mostly responsible for the production of strong antiviral factors - that is, type I interferons (IFNs) - in response to viruses. Their natural IFN production is impaired in chronic HIV infection, in correlation with viral load and disease progression, but it has not been tested during the critical stage of primary infection, when a balance is set between host immune responses and viral replication. Methods. We longitudinally studied 26 patients during the primary stage of HIV infection. Fifteen patients received highly active antiretroviral therapy (HAART) for 12 months. Results. At the time of inclusion into the cohort, median type I IFN production in response to herpes simplex virus type 1 stimulation was dramatically impaired in peripheral blood mononuclear cells (PBMCs) from HIV-infected patients, compared with that in PBMCs from 31 uninfected donors (180 vs. 800 IU/mL; P < .0001). Median circulating plasmacytoid DC counts were also significantly decreased (7300 vs. 13,500 cells/mL; P = .001). Twelve months later, IFN production returned to normal, and the data suggest that HAART may help in the recovery of IFN production by plasmacytoid DCs. Conclusions. These data underline the potential for early antiretroviral treatment and IFN-alpha treatment to enhance viral control in a larger proportion of patients during the critical stage of primary infection.