From the Guidelines
The pathophysiology of HIV/AIDS is characterized by the virus's destruction of the immune system, specifically targeting CD4+ T lymphocytes, leading to profound immunodeficiency and increased susceptibility to opportunistic infections and malignancies. The virus enters these immune cells by binding to CD4 receptors and co-receptors (CCR5 or CXCR4) on the cell surface, as described in the context of HIV drug resistance 1. Once inside, the virus uses reverse transcriptase to convert its RNA into DNA, which then integrates into the host cell's genome using the viral integrase enzyme. This integrated viral DNA directs the production of new viral particles, leading to cell death and the release of virions that infect additional cells.
The progressive depletion of CD4+ T cells results in several stages of HIV infection, including acute infection, clinical latency, and finally AIDS, defined by CD4+ counts below 200 cells/mm³ or the presence of opportunistic infections 1. Without treatment, the immune system gradually deteriorates, leaving the body vulnerable to opportunistic infections and malignancies that define AIDS. Key aspects of the pathophysiology include:
- The role of reverse transcriptase in converting viral RNA into DNA
- The integration of viral DNA into the host genome using integrase
- The production of new viral particles and cell death
- The establishment of latent reservoirs in long-lived cells, making eradication challenging even with antiretroviral therapy 1
The emergence of HIV drug resistance, as discussed in the context of antiretroviral therapy 1, further complicates the management of HIV/AIDS, highlighting the need for ongoing surveillance and adaptation of treatment strategies to combat resistance and prevent the progression to AIDS. The use of integrase inhibitor-based ART, such as dolutegravir-based regimens, has been shown to be effective in managing HIV infection and reducing the risk of drug resistance 1.
From the Research
Pathophysiology of HIV/AIDS
The pathophysiology of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is a complex process involving the destruction of the immune system, particularly the depletion of CD4+ T lymphocytes. The key aspects of this process include:
- Destruction of CD4+ T cells, which are crucial for the immune system's function 2, 3, 4, 5, 6
- Opportunistic infections and malignancies that occur as a result of the immune system's inability to fight off pathogens 2
- Chronic activation of the immune system, leading to immune suppression and the development of AIDS 3, 5
Mechanisms of CD4+ T Cell Depletion
The depletion of CD4+ T cells is a critical aspect of HIV/AIDS pathophysiology. Several mechanisms have been proposed to explain this depletion, including:
- Direct killing of infected cells by the virus 2
- Indirect mechanisms, such as apoptosis induced by HIV signaling through its cellular receptors 6
- Destruction of CD4+ T cells by monocytes armed with HIV envelope molecules 4
- Chronic activation of the immune system, leading to immune suppression and T cell depletion 3, 5
Clinical Manifestations
The clinical manifestations of HIV/AIDS are diverse and can be attributed to the immune system's inability to fight off opportunistic infections and malignancies. Common clinical features include:
- Opportunistic infections, such as pneumonia, dysphagia/odynophagia, diarrhea, and neurological symptoms 2
- Malignancies, such as Kaposi's sarcoma and non-Hodgkin's lymphoma 2
- Autoimmune diseases and other complications, such as immune thrombocytopenia (ITP) 2
Immune System Dysfunction
The immune system dysfunction in HIV/AIDS is characterized by: