HIV: Current Research
Open Access

Clinical Impact of Immune System Suppression in HIV

Abdul Squadron^{* *}Correspondence: Abdul Squadron, Department of Immunology, University of Chittagong, Chittagong, Bangladesh, Email:

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Description

The Human Immunodeficiency Virus (HIV) is a chronic, lifethreatening virus that primarily targets the immune system, particularly the CD4+ T cells, also known as helper T cells. Over time, HIV impairs the immune system, weakening the body's ability to fend off infections and diseases. When left untreated, HIV can progress to Acquired Immuno Deficiency Syndrome (AIDS), a condition characterized by severe immune suppression. This article delves into the mechanisms behind immune system suppression in HIV, the stages of the disease, and its clinical implications. HIV is a retrovirus, which means it stores its genetic information in RNA. Upon entering the host cell, it uses an enzyme called reverse transcriptase to convert its RNA into DNA, integrating it into the host’s genome. This viral DNA is then replicated along with the host's own DNA, leading to the production of new viral particles. HIV primarily targets CD4+ T cells, but it also affects macrophages and dendritic cells, which are key players in the immune response. By infecting and killing CD4+ T cells, the virus gradually diminishes the body's immune capacity. The destruction of these cells disrupts the communication and coordination of the immune system, leading to an increased susceptibility to opportunistic infections and cancers.

This occurs within 2 to 4 weeks after the virus enters the body. During this stage, HIV replicates rapidly, and the number of CD4+ T cells declines sharply. The immune system responds by producing HIV-specific antibodies, but these are not sufficient to control the infection. Symptoms during this stage are often flulike, including fever, swollen lymph nodes, and fatigue. During this phase, HIV continues to multiply but at lower levels. CD4+ T cell levels slowly decline, though many people remain asymptomatic or have mild symptoms. Without treatment, this phase can last for several years, during which the immune system is gradually weakened. This is the final stage of HIV infection. At this point, the immune system is severely compromised, with CD4+ T cell counts falling below 200 cells per cubic millimeter of blood. Opportunistic infections and cancers are common in individuals with AIDS, and without treatment, the condition is usually fatal. The suppression of the immune system in HIV infection occurs through several complex mechanisms:

The hallmark of HIV infection is the depletion of CD4+ T cells. HIV directly infects these cells by binding to the CD4 receptor and co-receptors CCR5 or CXCR4, gaining entry into the cell. Once inside, HIV replicates and kills the host cell. This destruction of CD4+ T cells occurs both through direct viral effects and indirectly by immune-mediated mechanisms. HIV also induces apoptosis (programmed cell death) in uninfected CD4+ T cells. The presence of viral proteins, particularly gp120, can trigger apoptosis in bystander cells, further exacerbating immune suppression. One of the paradoxes of HIV infection is that while the immune system is suppressed, it is also in a state of chronic activation. The constant presence of HIV particles, along with the destruction of immune cells, leads to a continuous immune response. This persistent activation results in immune exhaustion, where T cells become less effective over time. Chronic immune activation also leads to inflammation, which contributes to tissue damage and increases the risk of comorbidities such as cardiovascular disease. Elevated levels of pro-inflammatory cytokines, including TNF-alpha and IL-6, are commonly seen in individuals with HIV. HIV affects not only the quantity but also the quality of immune cells. CD8+ T cells, which are responsible for killing infected cells, become dysfunctional in chronic HIV infection. This is due to prolonged exposure to viral antigens, leading to a state of "T cell exhaustion." Exhausted CD8+ T cells express high levels of inhibitory receptors, such as PD-1, which impair their ability to eliminate HIV-infected cells.

Natural Killer (NK) cells, which are critical in early immune responses, also exhibit impaired function in HIV-infected individuals. This impairment reduces the body's ability to control viral replication and respond to infected cells. Lymphoid tissues, including lymph nodes and the Gut-Associated Lymphoid Tissue (GALT), are major sites of HIV replication. HIV rapidly depletes CD4+ T cells in the GALT, which leads to a breakdown of the mucosal barrier in the intestines. This allows bacterial products, such as lipopolysaccharides, to enter the bloodstream, further fueling immune activation and inflammation. The destruction of lymphoid tissues impairs the immune system's ability to regenerate and maintain a reservoir of functional immune cells. This leads to a progressive decline in immune competence over time. The suppression of the immune system in HIV has farreaching clinical consequences. Individuals with untreated HIV are susceptible to a range of opportunistic infections and malignancies. Some of the most common include:

These disorders range from mild cognitive impairment to severe dementia, affecting memory, attention, and motor function. Anti-Retroviral Therapy (ART) has revolutionized the treatment of HIV, transforming it from a fatal disease into a manageable chronic condition. ART consists of a combination of drugs that target different stages of the HIV life cycle, preventing the virus from replicating and reducing viral load to undetectable levels. One of the most significant benefits of ART is immune reconstitution. As viral replication is suppressed, CD4+ T cell counts gradually increase, restoring immune function. While ART cannot completely eradicate HIV from the body (due to the persistence of latent reservoirs), it allows the immune system to recover and reduces the risk of opportunistic infections and HIV-related cancers.

Conclusion

The Immune system suppression in HIV is a multifaceted process involving the direct destruction of CD4+ T cells, chronic immune activation, and the dysregulation of immune cell function. Without treatment, this leads to the development of AIDS, characterized by severe immunodeficiency and an increased risk of opportunistic infections and cancers. Antiretroviral therapy has significantly improved the prognosis for individuals with HIV, allowing for immune reconstitution and long-term viral suppression. However, the search for a cure and a preventive vaccine remains ongoing.