Acquired Immune Deficiency Syndrome

Abstract

Acquired immune deficiency syndrome (AIDS) is caused by the human immune deficiency viruses (HIV)‐1 and 2 discovered 30 years ago. AIDS is a life‐threatening disease which lacks either a cure or a protective vaccine. Yet, during the past three decades of HIV research, a great deal has been learned about HIV‐1 evolution, structure, replication cycle, pathogenicity and protection. These findings have led to the development of anti‐retroviral therapy (ART) which is capable of blocking viral replication, dramatically increasing life expectancy and preventing the progression to AIDS. However, there are significant problems associated with ART, not least the inability of ART to cure HIV infection and important questions remain regarding the mechanisms by which HIV‐1 cause's disease and the host and viral factors associated with protection. Recent research has revealed both pathogenic immune activation and viral latency as important processes established early during acute infection which drive chronic disease and prevent vaccination or cure. These insights into HIV infection are being harnessed to advance the development of immunotherapy to control the infection, identify and reactivate latently infected cells and design the new generation of vaccines needed to end the pandemic.

Key Concepts

  • HIV‐1 is the causative agent of AIDS
  • There is a great degree of diversity between strains of HIV‐1 and between HIV and SIV
  • Knowledge gained during the past 30 years has been essential in developing ART
  • ART has been very successful but is associated with significant problems that need to be addressed
  • HIV‐1 causes a multifaceted chronic activation of the immune system
  • Vaccination against HIV‐1 has so far failed
  • Combining different treatment arms including immunomodulation and activation of latency offers an opportunity to create a functional cure for HIV‐1

Keywords: AIDS; HIV‐1; T cell; immune activation; anti‐retroviral therapy; vaccine; immunotherapy; latency

Figure 1. The natural history of HIV‐1 infection. Infection is characterised by three phases. During the primary phase, HIV‐1 establishes infection and a sharp increase in virus replication coincides with decreases in the CD4+ T cell count and the onset of symptoms. After a few months, the virus reaches a ‘set point’ during which replication is met by a vigorous immune response. The asymptomatic phase can last between a few years to over a decade before the decline in CD4+ T cells allows for opportunistic infections, tumour progression and other HIV‐1‐associated co‐morbidities associated with AIDS. Markers of chronic immune activation such as increases in CD38 expression on CD8+ T cells is strongly associated with progression of disease and represents a better marker of disease progression than viral load.
Figure 2. Immune activation in the gut. HIV‐1 is rapidly transported to the gut possibly via none productively infected DCs. Here cytokine expression from activated monocytes and Paneth cells contributes to an inflammatory environment that damages the gut mucosa. Preferential infection and killing of Th17 and Th22 cells reduces gut maintenance and allows translocation of bacteria and LPS into the lamina propria. Infection of central memory (CM) CD4+ T cells associated with lymphoid tissue reduces the homeostatic control of T cell proliferation and the ratio of T cell subtypes such as Tregs and Th17 cells.
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Smith, Peter L, and Dalgleish, Angus(Nov 2015) Acquired Immune Deficiency Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000963.pub3]