Epidemiology: Open Access
Open Access

Human Immunodeficiency Virus (HIV) has had a profound impact on global health since it was first identified in the early 1980s. This virus targets the immune system, specifically the CD4+ T-cells, which play a central role in coordinating the body’s defense against infections. As HIV progresses to Acquired Immunodeficiency Syndrome (AIDS), the immune system becomes severely compromised, leaving individuals highly susceptible to a wide range of infections, cancers, and other complications. Over time, advancements in antiretroviral therapy (ART) have significantly improved the quality of life for people living with HIV, but the impact on immune system function remains a critical area of concern. This article examines the effects of HIV on the immune system, the mechanisms behind immune dysfunction in HIV-infected individuals, and the implications for treatment and management.

Description

HIV and immune system dysfunction

HIV attacks the immune system by targeting and infecting CD4+ T-cells, a critical component of adaptive immunity. CD4+ T-cells are responsible for orchestrating immune responses, including the activation of other immune cells like cytotoxic T-cells and B-cells. The virus binds to the CD4 receptor on these cells and uses them as host cells to replicate, ultimately leading to the depletion of CD4+ T-cells over time. As the CD4+ count drops, the body’s ability to mount effective immune responses diminishes, making individuals with untreated HIV highly vulnerable to opportunistic infections and cancers [1].

The progression from HIV infection to AIDS is marked by a significant reduction in CD4+ T-cell counts (typically below 200 cells/mm³), which severely impairs the immune system’s function. This depletion occurs not only due to direct viral replication but also as a result of the immune system’s inflammatory response to the ongoing infection. Chronic inflammation and immune activation contribute to immune system dysfunction in HIV, leading to an increased risk of infections and comorbidities such as cardiovascular disease, liver disease, and certain cancers.

Mechanisms of immune dysfunction in HIV

Depletion of CD4+ T-cells: The hallmark feature of HIV infection is the gradual destruction of CD4+ T-cells. As the virus replicates, it directly infects these cells and causes cell death, either through viral-induced apoptosis (programmed cell death) or by the body’s immune response against infected cells. Over time, the ongoing depletion of CD4+ T-cells impairs the immune system’s ability to respond to new infections or abnormal cells, leading to a weakened immune defense [2].

Additionally, HIV infection causes a decrease in the diversity of the T-cell receptor pool, which impairs the body’s ability to recognize and respond to a broad range of pathogens. This reduction in immune diversity, coupled with the loss of CD4+ T-cells, exacerbates the immunodeficiency associated with HIV.

Chronic immune activation and inflammation: One of the distinguishing features of HIV infection is chronic immune activation, even in the absence of opportunistic infections. HIV infection triggers an ongoing inflammatory response, which is thought to be a consequence of the body’s attempt to control the virus. However, prolonged inflammation can be damaging, contributing to immune system dysfunction and increasing the risk of comorbidities [3].

Chronic activation of the immune system leads to the accumulation of inflammatory cytokines and immune cells that can damage tissues and organs. This persistent inflammation is associated with accelerated aging, cardiovascular disease, and other complications commonly seen in individuals living with HIV. The imbalance in immune signaling further compromises the immune system’s ability to effectively fight infections and respond to vaccines.

Impaired immune responses to infections: As HIV progresses and CD4+ T-cell counts decrease, the body becomes more susceptible to infections, particularly those caused by opportunistic pathogens. Normally, the immune system can quickly recognize and eliminate these pathogens, but in individuals with HIV, this response is impaired. The diminished ability to mount effective immune responses makes people with HIV more prone to a range of infections, including bacterial, viral, fungal, and parasitic infections [4].

In addition to opportunistic infections, HIV-infected individuals are also at greater risk of developing certain cancers, such as Kaposi’s sarcoma, non-Hodgkin lymphoma, and invasive cervical cancer. The immunodeficiency caused by HIV, combined with chronic immune activation, creates a permissive environment for the development and progression of malignancies.

Antibody dysfunction and humoral immunity impairment: While T-cells play a central role in fighting infections, B-cells and antibodies are crucial for defending against extracellular pathogens, including bacteria and viruses. In individuals with HIV, B-cell dysfunction occurs as a result of both direct viral effects and the depletion of CD4+ T-cells, which are essential for B-cell activation and antibody production.

The resulting impairment of humoral immunity makes it harder for people living with HIV to produce effective antibodies in response to infections or vaccinations [5]. This deficiency further compromises the immune response and makes it more difficult for individuals with HIV to control infections, even when they are treated with ART.

The role of antiretroviral therapy (art) in modulating immune function

Antiretroviral therapy (ART) has been a transformative advancement in the treatment of HIV. ART works by inhibiting various stages of the HIV replication cycle, reducing the viral load in the body, and slowing the progression of the disease. One of the key benefits of ART is its ability to prevent further depletion of CD4+ T-cells, allowing the immune system to recover to some degree.

While ART does not cure HIV, it has been shown to improve immune function significantly, reducing the risk of opportunistic infections and cancers. In many cases, ART can restore CD4+ T-cell counts to near-normal levels, although the immune system may never fully return to its pre-infection state. Furthermore, ART helps to reduce chronic inflammation and immune activation, which can mitigate some of the long-term health risks associated with HIV.

However, even with ART, individuals living with HIV often experience a range of long-term health challenges, including cardiovascular disease, liver disease, and certain cancers. These complications are thought to arise from both the direct effects of the virus and the chronic immune activation that persists even when viral replication is suppressed [6].

Conclusion

HIV continues to have a profound impact on immune system function, leading to immunodeficiency and a range of associated health complications. The virus primarily targets CD4+ T-cells, disrupting the body’s ability to fight infections and increasing susceptibility to opportunistic infections and cancers. Chronic immune activation and inflammation exacerbate immune dysfunction, and despite the effectiveness of ART in managing HIV, many individuals still experience long-term health issues related to immune system dysregulation. As treatment options continue to improve and as our understanding of HIV’s impact on the immune system deepens, there is hope for even more effective therapies that can better restore immune function and reduce long-term complications. Continued research into immune modulation, potential vaccines, and curative strategies for HIV will be critical in improving the health and quality of life for individuals living with the virus. In the meantime, managing HIV as a chronic, treatable condition with ART remains the cornerstone of care, while ongoing efforts to address the broader implications of immune dysfunction in HIV-positive individuals will be crucial for improving outcomes in the long term.

Acknowledgement

None

Conflict of Interest

None

References

1. Higuita NIA, Brunetti E, McCloskey C (2016) Cystic Echinococcosis. J Clin Microbiol 54: 518-523.

Indexed at, Google Scholar, Crossref

2. Harrison MS, Goldenberg RL (2016) Global burden of prematurity. Semin Fetal Neonatal Med 21: 74-79.

Indexed at, Google Scholar, Crossref

3. Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC (2018) Estimating the global incidence of traumatic brain injury. J Neurosurg 130: 1080-1097.

Indexed at, Google Scholar, Crossref

4. Fuller R, Landrigan PJ, Balakrishnan K, Bathan G, Bose-O'Reilly S, et al. (2022) Pollution and health: a progress update. Lancet Planet Health 6: e535-e547.

Indexed at, Google Scholar, Crossref

5. Marešová P, Mohelská H, Dolejš J, Kuča K (2015) Socio-economic Aspects of Alzheimer's Disease. Curr Alzheimer Res 12: 903-911.

Indexed at, Google Scholar, Crossref

6. Thayabaranathan T, Kim J, Cadilhac DA, Thrift AG, Donnan GA, et al. (2022) Global stroke statistics 2022. Int J Stroke 17: 946-956.

Indexed at, Google Scholar, Crossref