Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy

Abstract

Globally, human immunodeficiency virus type 1 (HIV-1) infection is a major health burden for which successful therapeutic options are still being investigated. Challenges facing current drugs that are part of the established life-long antiretroviral therapy (ART) include toxicity, development of drug resistant HIV-1 strains, the cost of treatment, and the inability to eradicate the provirus from infected cells. For these reasons, novel anti-HIV-1 therapeutics that can prevent or eliminate disease progression including the onset of the acquired immunodeficiency syndrome (AIDS) are needed. While development of HIV-1 vaccination has also been challenging, recent advancements demonstrate that infection of HIV-1-susceptible cells can be prevented in individuals living with HIV-1, by targeting C-C chemokine receptor type 5 (CCR5). CCR5 serves many functions in the human immune response and is a co-receptor utilized by HIV-1 for entry into immune cells. Therapeutics targeting CCR5 generally involve gene editing techniques including CRISPR, CCR5 blockade using antibodies or antagonists, or combinations of both. Here we review the efficacy of these approaches and discuss the potential of their use in the clinic as novel ART-independent therapies for HIV-1 infection.

Plasma interleukin-7 correlation with human immunodeficiency virus RNA and CD4+ T cell counts, and interleukin-5 with circulating hepatitis B virus DNA may have implications in viral control

“…Macrophage inflammatory protein-1 beta, also known as CCL4 binds CCR5 naturally to inhibit HIV fusion given that R5-tropic HIV-1 infects T cells via the CCR5 co-receptor ( 74 ). The high levels of MIP-1β seen among all the viral infection groups is suggestive of the magnitude of inflammation that may have implications, both protective or pathological.…”

Punica granatum as Anticandidal and Anti-HIV Agent: An HIV Oral Cavity Potential Drug

“…Consequently, to achieve pharmacological success, many factors are involved, including the following: correct patient adherence to antiretroviral (ART) treatment; the availability of antiretroviral drugs; distribution of antiretrovirals; the development of HIV-resistant genotypes, among others. Thus, novel anti-HIV-1 drugs that can be effective in treating acquired immunodeficiency syndrome (AIDS) progression are needed [ 24 ]. In this case, the metabolites of certain plants could be a possible alternative.…”

A systematic review of gene editing clinical trials

“…In addition, people who use the same HIV drugs may have different side effects (HIVinfo.nih.gov, 2021). Challenges facing current medications that are part of lifelong antiretroviral therapy (ART) include toxicity, the development of drug-resistant HIV-1 strains, treatment cost, and the inability to eradicate the provirus from infected cells (Mohamed et al, 2021).…”

“…According to the statistics published by the World Health Organization (WHO) in 2021, the number of HIV-infected people worldwide was 38.4 million, of which 650,000 died (World Health Organization, 2022c). Human immunodeficiency virus type 1 (HIV-1) infection is a global health problem, and successful treatment options are still under investigation (Mohamed et al, 2021). Different drugs available in treating patients with HIV can cause various side effects.…”

“…According to the above-mentioned challenges, new anti-HIV-1 treatments that can prevent the progression of the disease, especially the onset of the AIDS, or eliminate it, are needed. While the development of an HIV-1 vaccine has also been challenging, recent advances suggest that it is possible to prevent infection of HIV-1-susceptible cells in HIV-1-infected individuals by targeting the chemokine receptor type 5 (CCR5) (Mohamed et al, 2021). CCR5 is the major receptor for the human immunodeficiency virus (HIV) (Tebas et al, 2014).…”