H uman Immunodeficiency Virus ( HIV )

Abstract

Human immunodeficiency virus (HIV) is the aetiological agent of the acquired immune deficiency syndrome (AIDS). Without treatment, most subjects develop severe disease and die within approximately 10 years of the infection. HIV‐related disease has two interrelated mechanisms of pathogenesis: immune activation with inflammation and progressive immune deficiency. Antiretroviral therapy (ART) effectively suppresses HIV replication and prevents disease progression and death. Treatment regimens are mainly based on combinations of three antiretroviral agents with two different mechanisms of action, chosen from drug classes that target different steps in the virus replication cycle. People that maintain excellent adherence to treatment enjoy long and healthy lives and are at little risk of developing drug resistance or transmitting the infection to contacts. During ART, however, HIV persists by integrating within the deoxyribonucleic acid (DNA) of long‐lived memory CD4 T cells. Research is actively pursuing strategies to cure HIV infection by eradicating or silencing integrated virus and inducing immune control. Key Concepts HIV infection is a zoonosis that resulted from transmission to humans of viruses found in African monkeys and apes. Circulating strains are characterised by an incredible amount of genetic variation, upon which evolutionary forces can act. The natural course of HIV infection is characterised by progressive immune dysfunction. The impact of HIV on the immune system comprises chronic immune activation, abnormal T‐cell responses and cytokine production, progressive T‐cell exhaustion and CD4 cell loss occurring mostly through apoptosis. Antiretroviral treatment is lifelong. Consistently high levels of adherence are required to prevent virus escape and emergence of drug resistance. HIV has found several ways of evading immune responses and exploits physiological processes to ensure persistence in infected hosts. Integrated virus can persist long term in a dormant state, ready to reactivate under the appropriate circumstances. This reservoir is invisible to the immune system and unresponsive to antiretroviral therapy. How the HIV reservoir is maintained despite antiretroviral therapy is not completely understood. Mechanisms may include expansion through proliferation of latently infected CD4 T cells without virus production and replenishment through ongoing virus production in body compartments where antiretroviral drugs have reduced penetration or activity. The most effective way of containing the spread of HIV combines prevention of acquisition through personal protective measures and prophylactic use of antiretroviral therapy and prevention of transmission through prompt diagnosis and early treatment of those who become infected. There is cautious optimism, based on emerging research data, that both a prophylactic vaccine and a cure for those already infected may 1 day become available.