Autoantibodies neutralizing type 1 interferons in two cohorts of people with HIV

Autoantibodies (autoAbs) neutralizing type I interferons (IFN-I) markedly increase the risk of severe manifestations of some viral diseases. The prevalence of autoAbs neutralizing at least one IFN-I, specifically IFN-α2, IFN-β, and IFN-ω, in individuals from the Swiss human immunodeficiency virus 1 (HIV-1) cohort is largely similar to French age-matched healthy controls, with around 1% in adults by age 65 having neutralizing IFN-I autoAbs and rising thereafter. We analyzed samples from Danish individuals with HIV, including antiretroviral therapy (ART) treated (<i>n</i> = 260) and ART-naive (<i>n</i> = 58) individuals, aged 18-79 (mean age 46.6 years, SD ± 11.1 years), and American individuals with HIV, all of whom were ART-naive (<i>n</i> = 292) aged 20-76 (mean age 41.7 years, SD ± 10.1 years). In the Danish cohort, a total of 2/318 (0.63%) individuals had autoAbs neutralizing 1 ng/ml IFN-ω, whereas 1/318 (0.31%) had autoAbs neutralizing 200 pg/ml IFN-ω. In the American cohort, 2/292 (0.68%) individuals had autoAbs neutralizing IFN-ω at 1 ng/ml. Combining both cohorts, the overall prevalence of autoAbs neutralizing IFN-ω was 5/610 (0.82%). Longitudinal samples were available for two individuals with IFN-ω autoAbs: One displayed persistently detectable autoAbs over time, whereas the other showed a decline in neutralizing activity after 2 years. Two out of five individuals with IFN-I neutralizing autoAbs had a history of IFN-α treatment for chronic hepatitis C virus (HCV) infection. Individuals with IFN-I neutralizing autoAbs shared a history of viral infections, including mucocutaneous herpesvirus infections, zoster, and human papillomavirus disease. Collectively, the prevalence of IFN-I neutralizing autoAbs in people with HIV, whether ART-treated or ART-naive, did not significantly differ from that in the general population. Whereas hepatitis C and IFN therapy may contribute to the development of autoAbs to IFN-I, these autoAbs in turn seem to predispose to mucocutaneous herpesvirus infections and HPV-related neoplasia.