HIV: Current Research
Open Access

Identification of HIV-Related Antibody Responses and Inflammatory Responses, and Therapeutic Interventions

Babu Tenzing^{* *}Correspondence: Babu Tenzing, Department of Pharmaceutical Chemistry, Mid-West University Central Office, Birendranagar, Nepal, Email:

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Description

Although Human Immunodeficiency Virus (HIV) replication is effectively controlled by antiretroviral therapy, a persistent immune activation/inflammation remains throughout the illness. One of the main causes of CD4⁺ T cell depletion and an accelerator of non-AIDS-related events are these abnormal immune activation and inflammation. Unfortunately, a number of factors contribute to immunological activation linked with HIV, although the exact cause of increased inflammation is yet unknown. To date, a number of clinical therapies or treatment options are being tested in clinical settings to address this systemic immune activation/inflammation.

These tactics, however, had mixed results, or they had general anti-inflammatory qualities that were similar to those of earlier therapies. In this article, we evaluated new findings about immune activation, ongoing inflammation, and HIV infection as well as the current approaches to treating it. It is important to emphasize that developing a successful clinical intervention plan still requires a deeper comprehension of the precise mechanisms behind abnormal inflammation.

HIV/AIDS was formerly a lethal illness, but with the introduction of well-tolerated and highly efficient Antiretroviral Therapy (ART), it has become a chronic and manageable condition. As a result, the life expectancy of HIV-infected individuals with a high CD4⁺ T cell count and an undetectable viral load after ART is slowly catching up to that of the general population. However, the entire infection process is accompanied by aberrant immunological activation and inflammation, making it difficult for antiviral medication to treat these clinical issues on its own. People living with HIV (PLWH) demonstrated increased levels of immunological activation, as seen by heightened levels of biomarkers such IL-6, D-dimer, CReactive Protein (CRP), and sCD14, even after effective antiretro viral therapy.

HIV infection is characterized by chronic immune system activation, which is a stronger indicator of disease prognosis than plasma viral load. Clinical data, however, indicated that only up to 30% of patients after ART showed a minor increase in CD4⁺ T cell numbers, far from the threshold required for successful immunological reconstitution. Additionally, the progression of the disease in PLWH is correlated with inflammation levels, which foretells an accelerated and accentuated onset of Serious Non-Aids Events (SNAEs), including neurocognitive disorders, coronary artery disease, chronic liver/kidney dysfunction, metabolic syndrome, osteoporosis, and non-HIV-associated cancers. Patients are therefore more likely to experience disease progression and unfavorable outcomes in this situation, as well as continued susceptibility to opportunistic infections.

Undoubtedly, one key factor in HIV-related immunological activation and inflammation is the HIV-1 reservoir's persistence following ART. However, immunological activation and inflammation associated with HIV are a systematic and protracted process in which other additional variables and processes also play a role. Treatment for aberrant immune activation and inflammation has gradually become necessary due to its complexity and stress on patients, and therapeutic trials using anti-inflammatory characteristics are being conducted to stop this condition. The current mechanisms and therapeutic approaches/drugs for HIV-related immune activation and inflammation will be thoroughly explained in this review. Following HIV antigenic stimulation, T cells become activated, triggering both the innate and adaptive immune response. However, even when the HIV-1 viral load dropped to an undetectable level, the immune system is still activated. Numerous theories have been put out up to this point on the complicated underlying mechanisms of persistent immunological activation.

The fraction of CD8⁺T cells overexpressing CD38, the blood level of IFN, and prolonged failure during CD4⁺ T cell reconstitution in treated individuals are all related to the microbial translocation. On the other hand, intestinal epithelial cell death and the intestinal mucosa's high level of inflammation both contributed to the promotion of intestinal microbial translocation. Therefore, immunological and inflammatory activity is substantially connected with dysregulation of intestinal microbial and microbial translocation. During chronic HIV infection, the location of Treg cells, a powerful natural regulator, shifted, and this was accompanied by a transfer of CD4⁺ CD25⁺ Treg from peripheral blood to peripheral lymph nodes and mucosal lymphoid tissues.

Through contact-dependent processes, Treg cells can prevent T cell activation and proliferation, but they are also susceptible to HIV infection, which has a severe negative impact on their functionality. Treg cells were said to inhibit the generation of IL-2, which in turn regulates immunological activation during HIV-1 infection.

Reduced Treg cells are significantly linked to immunological activation and can raise the risk of atherosclerosis and other related inflammatory illnesses, even in HIV elite controllers. In other words, the current clinical trials using Treg cells are based on the hypothesis that increasing Treg cells may lower HIVassociated immunological activation.

Conclusion

In conclusion, even though numerous pathogeneses of HIVrelated immune activation and inflammation, including the HIV-1 reservoir, coinfections, and various inflammatory signaling, have been clarified, the current understanding of this complex disease still falls short of the requirement to develop specialized therapeutic modalities. Additionally, circumstances unrelated to AIDS hastened the disease's development. Despite the fact that several methods and plans have been put up for curing HIV, no workable answer has yet been found. Therefore, on the one hand, it is still essential to gain a deeper understanding of the specific pathophysiology or their interaction that results in aberrant immune activation/ inflammation associated with HIV. On the other hand, early medication intervention before the HIV reservoir is formed may be a successful tactic.