Targeting CCR5: A central approach to HIV treatment and cure strategies

CCR5, a co-receptor critical for R5-tropic HIV entry into host cells, remains a key target for therapeutic interventions. HIV utilizes CCR5, expressed on T cells and macrophages, to facilitate viral entry. Genetic variants, such as the CCR5 Delta 32 homozygous mutation that confers protection to HIV infection, have made CCR5 a main target for gene-editing technologies, small-molecule inhibitors, and monoclonal antibody-based therapies. Recent studies emphasize the importance of regulating CCR5 expression at transcriptional and post- transcriptional levels and integrating this approach with traditional therapies. Particularly, the role of heterozygous CCR5 Delta 32 carriers who are HIV seropositive highlights the potential for targeting CCR5 in combination with other immune-regulatory mechanisms. This may lead to more effective treatment strategies and, ultimately, a functional cure for HIV. This minireview discusses the role of CCR5 in HIV pathogenesis and explores the potential of genetic and therapeutic interventions targeting CCR5 as an innovative strategy in the continued battle against HIV.