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 CCR5Δ32 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 CCR5Δ32 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. •HIV remains a global health issue, affecting around 40 million people worldwide.•CCR5, a key co-receptor for HIV entry, is a critical target for therapies aimed at blocking the virus and preventing infection.•The CCR5-Δ32 mutation, both in homozygous and heterozygous, offers resistance to HIV, inspiring new genetic treatments and stem cell therapies.•Maraviroc and monoclonal antibodies show promise but face challenges like resistance and limited efficacy.•CRISPR/Cas9 technology represents an innovative approach, potentially leading to a functional HIV cure.