Under the Radar: Immune Evasion, Pathogenesis and Control of HIV Infection

The human immunodeficiency virus (HIV) is a retrovirus discovered in 1983 as the causative agent of acquired immunodeficiency syndrome (AIDS). Following several zoonotic spillover events from non-human primates, the virus spread between humans for more than 60 years under the radar. HIV infects and kills CD4 T cells, the cells that coordinate adaptive immune responses. Primoinfection is associated with a flu-like symptomatology and chronic infection is clinically silent, and mostly not diagnosed, contributing to viral spread and leading to fatal long-term outcomes. HIV genome codes for a poor reading-proof reverse transcriptase, which facilitates high sequence variability, particularly in the envelope glycoprotein complex, the sole external viral protein and main target of humoral immune responses. This antigenic variability precludes the development of an efficacious vaccine despite 40 years of research. In contrast, the development of antiretroviral drugs represents a scientific and medical success which saved the lives of millions of infected people and provides today an excellent protection against AIDS, although it does not permit viral eradication. Indeed, HIV can integrate its genome in target cells and generates a pool of latently infected cells which escape eradication by both the natural immune response and treatments. In summary, the efforts to tackle HIV have been suboptimal, and the virus has infected more than 90 million people and caused 44 million deaths worldwide. In the absence of a vaccine, a better deployment of available preventative and therapeutic tools is needed, particularly in geographical areas and communities with the highest incidence of infection.