The Forgotten Virus, Hepatitis D: A Review of Epidemiology, Diagnosis, and Current Treatment Strategies.

Hepatitis D virus (HDV) is an RNA subvirus that infects patients with co-existing hepatitis B virus (HBV) infections. HDV burden is estimated to be approximately 15-20 million people worldwide. Despite HDV severity, screening for HDV remains inadequate. HDV screening would benefit from a revamped approach that automatically reflexes testing when individuals are diagnosed with HBV if HBsAg-positive, to total anti-HDV, and then to quantitative HDV-RNA polymerase chain reaction (PCR) rather than only testing those at high risk sequentially. There are no current treatments in the United States that are Food and Drug Administration (FDA)-approved for the treatment of HDV; however, bulevirtide (BLV) is approved in the European Union conditionally and is under review with the United States FDA. Current treatment strategies in many countries are centered on the use of pegylated-interferon-alfa-2a (PEG-IFNa-2a). There are other therapies in development globally that have shown promise, including BLV, pegylated-interferon-lambda (PEG-IFN-lambda), and lonafarnib (LNF). LNF has shown substantial response in the LOWR trials. BLV is a well-tolerated drug, but it is not finite therapy and has shown significant on-treatment responses in the MYR clinical trials, and the FDA cited concerns with the manufacturing and patient preparation of the drug that have delayed approval. The PDUFA date for BLV in the United States is mid-2024. Current studies with both BLV and LNF are limited in providing sustained virological response (SVR); future trials will need to demonstrate more substantial SVR with possible triple combination trials as options.

Plasma tissue factor and immune activation are associated with carotid intima-media thickness progression in treated HIV infection.

OBJECTIVES: We evaluated the roles of biomarkers of immune activation with carotid intima-media thickness (CIMT) progression in treated HIV infection. DESIGN: Longitudinal observational study of 118 treated and virologically suppressed individuals. METHODS: We measured biomarkers of immune activation at baseline using cryopreserved samples. CIMT was measured at baseline and longitudinally using high-resolution ultrasound. Linear regression was used to estimate biomarker associations with CIMT progression, and logistic regression was used to model plaque progression. RESULTS: The median duration of follow-up was 2.0 years. The median annual rate of change in mean CIMT was 6.0%. Rates of progression were more rapid in the bifurcation (5.6%/year, P = 0.006) and internal (6.5%/year, P = 0.0008) than common CIMT (4.3%/year). Incident plaque occurred in 13 of the 52 individuals without baseline plaque. In multivariable adjusted analysis, plasma tissue factor and monocyte chemoattractant protein-1 were associated with more rapid common CIMT progression (0.058 mm/year, P = 0.0004 and 0.067 mm/year, P = 0.017; all estimates per doubling). CD8 T-cell count and percentage of HLA-DRCD38CD8 T cells were associated with more rapid internal CIMT progression (0.10 mm/year, P = 0.008 and 0.054 mm/year, P = 0.045). CD8 T-cell count was also associated with 0.068 mm/year more rapid mean CIMT progression (P = 0.011). Each 10% increase in CD4 T-cell count at baseline was associated with a 34% reduced odds of plaque progression (P = 0.018). CONCLUSION: Residual immune activation and plasma tissue factor are independently associated with CIMT progression in treated HIV infection. Interventions targeting coagulation and inflammatory pathways to reduce cardiovascular disease risk in HIV merit additional investigations.