Abstract Innate immunity represents the first line of defence against viral infections, and successful pathogens like HIV-1 have evolved mechanisms to bypass these barriers. The PAF1 complex (PAF1c) has emerged as a key regulator of antiviral innate immune responses, inhibiting the replication of various viruses, including HIV-1. While its role in transcription regulation is well documented, little is known about how PAF1c inhibits HIV-1 and how HIV-1 circumvents this antiviral activity.