Khadija Khalid

Hepatitis B virus (HBV) infection is a worldwide health concern that infects nearly 254 million people globally and causes more than 1 million deaths annually. The highest prevalence is seen in sub-Saharan Africa and the Western Pacific region. Cirrhosis, liver failure, and hepatocellular carcinoma (HCC) are reported as leading complications of chronic HBV. The route of transmission of this infection is mainly by exposure to infected blood and bodily fluids. Transmission from mother-to-child remains the predominant route in highly endemic areas. Vaccination has significantly reduced HBV seroprevalence and complications. However, incomplete vaccination of newborns continues to be a major obstacle to elimination of the disease. Current prevention strategies include universal vaccination, perinatal prophylaxis with hepatitis B immune globulin, and maternal antiviral therapy in pregnant women with high viral load. The management of chronic hepatitis B virus infection predominantly depends on nucleoside analogs, including entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide, as well as pegylated interferon alfa. These therapies effectively suppress viral replication and reduce the risks of cirrhosis, HCC, and liver-related mortality, but they rarely achieve functional cure characterized by hepatitis B surface antigen loss. The persistence of covalently closed circular DNA (cccDNA) remains a major hindrance in HBV eradication. Therefore, novel therapeutic strategies targeting different stages of the viral life cycle, including capsid assembly modulators, small interfering RNAs, nucleic acid polymers, and cccDNA-directed approaches, are under active investigation. This review summarizes the epidemiology, prevention, current therapies, clinical outcomes, and emerging therapeutic advances in HBV infection, highlighting ongoing efforts toward achieving a functional cure and global HBV elimination.

The C-C chemokine receptor type 5 (CCR5) is the principal co-receptor for R5-tropic HIV-1 and remains one of the most promising therapeutic targets in the pursuit of an HIV cure. The discovery that individuals carrying the naturally occurring CCR5Δ32 mutation exhibit marked resistance to HIV infection established the foundation for both genetic and pharmacological approaches to CCR5 inhibition. This review summarizes recent advances in CCR5-targeted therapies with a focus on CRISPR/Cas9-mediated gene editing and maraviroc-mediated receptor blockade. We discuss the molecular mechanisms, preclinical evidence and emerging clinical data supporting CRISPR-based CCR5 disruption, including multiplex editing strategies designed to overcome viral tropism switching. We also examine the evolving role of maraviroc beyond viral entry inhibition, highlighting its immunomodulatory effects, potential latency-reversing activity and applications in graft-versus-host disease and cancer. Together, these complementary strategies underscore the potential of CCR5-targeted interventions as integral components of future combination therapies aimed at achieving durable HIV remission or functional cure.

C-C chemokine receptor type 5 (CCR5) is the primary co-receptor mediating the entry of R5-tropic human immunodeficiency virus type 1 (HIV-1) into CD4+ T cells and macrophages, making it one of the most promising therapeutic targets in HIV cure research. The naturally occurring CCR5Δ32 mutation which abolishes surface CCR5 expression in homozygous individuals has provided strong clinical evidence for CCR5-directed strategies after multiple cases of sustained HIV remission following allogeneic hematopoietic stem cell transplantation (HSCT) from CCR5Δ32 donors. This review summarizes the current understanding of the evolutionary origin and global distribution of the CCR5Δ32 allele, as well as the clinical evidence from landmark transplantation cases. We also discuss recent findings demonstrating that durable HIV remission may be achieved following transplantation from heterozygous CCR5 wild-type/Δ32 donors, suggesting that factors such as donor chimerism, conditioning regimens and graft-versus-reservoir effects contribute substantially to reservoir clearance alongside CCR5 disruption. In addition, we examine emerging evidence that pharmacological inhibition of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway can reversibly suppress CCR5 expression, reduce HIV replication, limit reservoir establishment, and attenuate immune activation. Collectively, these advances highlight the evolving landscape of CCR5-targeted therapies and support the development of safer and more broadly applicable approaches toward durable HIV remission and, ultimately, an HIV cure.