Disclosures: Chung reports receiving research grants from AbbVie, BMS, Boehringer Ingelheim, Gilead, GSK, Janssen, Merck and Roche.
January 10, 2022
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Q&A: HIV links to diminished control of HBV coinfection

Disclosures: Chung reports receiving research grants from AbbVie, BMS, Boehringer Ingelheim, Gilead, GSK, Janssen, Merck and Roche.
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Novel hepatitis B virus RNA and HBV core-related antigen blood assays revealed continued disease activity despite apparently suppressed virus replication among patients dosed with antiviral therapy for HBV and HIV coinfection.

Aimed to investigate the association between HBV RNA and HBV core-related antigen (HBcrAg) with classical HBV biomarkers, liver histology and staining, researchers analyzed 95 patients (median age, 50 years) coinfected with HBV and HIV. They collected demographic, clinical, serological and virological data at baseline and every 24 weeks to 48 weeks for up to 192 weeks.

“We need to continue antiviral therapy and maintain vigilance for risk of progressive liver disease in our HBV/HIV-coinfected patients as the new assays suggest that continued disease activity occurs despite apparently suppressed HBV replication using available treatment.” Raymond T. Chung, MD

Among hepatitis B e antigen-positive patients, the study revealed declines in HBV RNA and HBcrAg as well as HBeAg, hepatitis B surface antigen, HBV DNA and hepatitis B core antigen (HBcAg) hepatocyte staining grade (P < .05 for all). Researchers observed no significant decline among HBeAg-negative patients for HBV RNA (P = .49) and HBcrAg (P = .63).

Raymond T. Chung, MD, chief of hepatology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, spoke with Healio about the importance of these findings and how it informs patient care going forward.

Healio: Why did your team undertake this investigation?

Raymond T. Chung: Chronic HBV infection affects more than a quarter billion persons worldwide and is a major cause of liver cirrhosis, liver cancer and death. In

persons living with HIV, the trajectory of chronic HBV is even more accelerated, despite the advent of effective suppressive antiviral therapy against both viruses. Until now, the most reliable blood markers of HBV DNA assays provided a picture of the level of replication of HBV. However, they may not differentiate those infections with active transcription and translation of viral proteins from those that are inactive and these may have implications for liver damage long term.

New blood assays, called HBV RNA and HBcrAg, have been developed to provide a window into these processes. Our prior work had demonstrated that in HBV/HIV-coinfected persons, there is a persistent activity of HBV RNA and HBcrAg that may correlate with increased viral activity in the liver not captured by HBV DNA tests.

In this study, we asked how these markers change over time (nearly 4 years) in those patients who remain on suppressive dually active antiviral therapy against both HBV and HIV.

Healio: What is the most important take-home message?

Chung: Despite the high frequency of the suppressed phenotype and long treatment, we observed continued decline in markers of HBV transcription/translation in HBeAg-positive patients (who harbor a higher level of HBV in general) and a plateauing of these markers in HBeAg-negative patients (who have lower levels of HBV). This finding is noteworthy in that the ostensible control reflected by undetectable HBV DNA testing does not reflect the continued slow or stalled decline of HBV transcription and translation in the context of HIV coinfection.

These findings suggest that HIV infection is associated with diminished control of HBV infection and provides a basis by which HBV-related liver damage may be more progressive in patients with HIV compared to those without HIV.

Healio: How do these results inform management for HBV/HIV-coinfected patients going forward?

Chung: The findings suggest a possible utility of these new assays for tracking of HBV, particularly in HBeAg-positive chronic HBV/HIV-coinfected patients, in whom declines in these markers are observed over time. They also underscore the importance of continued antiviral therapy against HBV in this group of patients, whether HBeAg-positive or HBeAg-negative. Most importantly, they highlight a pressing need for agents that promote functional cure of HBV to eliminate the risk of progressive liver disease in HBV/HIV-coinfected persons.

Healio: What additional research, if any, is needed?

Chung: We need to develop additional classes of therapy that help us achieve functional cure of HBV to truly arrest the natural history of liver damage, particularly in HBV/HIV-coinfected persons, in whom progression may continue despite apparent viral suppression. Trials of several new classes of anti-HBV therapy are currently underway.

Healio: What advice would you give to clinicians treating this subgroup of patients?

Chung: We need to continue antiviral therapy and maintain vigilance for risk of progressive liver disease in our HBV/HIV-coinfected patients as the new assays suggest that continued disease activity occurs despite apparently suppressed HBV replication using available treatment.