Each year on TheBodyPro, we review the new research and critical events of the past 12 months that have had—or will have—the greatest impact on the way we provide HIV care and services in the U.S. This article is part of a series examining the most noteworthy clinical developments of 2023.
Having evidence in the blood of the antibody to the hepatitis B virus (HBV) core is a long-lasting sign of prior infection. About 4% of people with HIV in the U.S. have a positive HBV core antibody (cAb+); worldwide, the rate is much higher, at about 30%. Isolated cAb+ is sort of a limbo state in which there is usually no evidence of the virus in the blood but also none of the surface antibodies that are associated with protection from reactivation. Most people in this situation do not experience a reactivation of HBV, but they can, especially when immunosuppressed.
For people with HIV treated with tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) along with either emtricitabine (FTC) or lamivudine (3TC), there is not too much concern about HBV core antibody positivity, as the combinations of these pairs are highly effective against HBV. However, as dual HIV therapy options emerge that are free of HBV-active agents, [SY1] there is the potential that HBV reactivation could follow a switch.
To quantify this, researchers from the Department of Veterans Affairs, reporting at IDWeek 2023, examined data from 60,290 people living with HIV in the Veterans Aging Cohort Study (VACS), of whom 20,941 were cAb+. Of these cAb+ patients, 5,954 switched to an antiretroviral therapy devoid of tenofovir, 3TC, or FTC and were at risk for HBV reactivation by virtue of being negative for HBV surface antigen (otherwise they would be active HBV cases) and having undetectable HBV DNA (if checked).
Using an outcome of new surface-antigen positivity or new HBV DNA detection, 89 of the 5,954 (1.5%) patients switching from an HBV-active regimen experienced HBV reactivation. That seems more than trivial; however, the investigators went on to exclude those with HBV reactivation after they restarted on HBV-active HIV therapy or had stopped antiretrovirals altogether, arriving at 39 cases (0.7%). The median time to reactivation was 292 days. Those who had ever had a prior detected surface antigen seemed more at risk.
The Bottom Line: Consider the Potential Return of HBV When HIV Regimens Are Simplified
This retrospective analysis highlights an important risk that HIV clinicians in the U.S. have not concerned themselves with much. As HBV is uncommon among people with HIV in the U.S., it is typically out of mind if out of sight. However, this has been a luxury afforded by the two-birds-with-one-stone antiretrovirals we use to treat both viruses. With combinations such as cabotegravir (CAB) and rilpivirine (RPV), dolutegravir (DTG) and RPV, and maybe even DTG and 3TC, we are leaving HBV uncovered.
For those with isolated cAb+, the risk of reactivation is low but not zero, this study shows. Further, among the cases, this was not exactly a mild reactivation. The majority had elevations of ALT levels to greater than 100 mg/dL, and 40% were hospitalized within 30 days of reactivation of HBV. Even if the risk is one out of 100, the risk of a return of HBV should be included in discussions about regimen simplification in those with cAb+.