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AntiHBc and HIV Virologic Suppression EACS
Should We Worry About Hepatitis B Core Antibody Before ART Switch?

Released: November 13, 2023

Karine Lacombe
Karine Lacombe, MD, PhD
Activity Information

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Key Takeaways
  • In a retrospective cohort study, positive hepatitis B core antibody was associated with failure to achieve HIV virologic suppression in people living with HIV who were switched to DTG/3TC.
  • Caution should be used with positive hepatitis B core antibody before switching ART to 2-drug regimens.

Because of their similar routes of transmission, nearly 10% of people living with HIV worldwide also live with hepatitis B virus (HBV) infection. People with a positive hepatitis B core antibody (anti-HBc) are at risk for HBV reactivation. This is of concern for people living with HIV, as initiation or discontinuation of HBV-active antiretroviral therapy (ART) can cause liver-related complications attributed to HBV flares. 

Tenofovir, emtricitabine, and lamivudine (3TC) are often components in ART regimens and are also recommended for those with HBV infection. However, newer 2-drug ART regimens such as cabotegravir plus rilpivirine or dolutegravir (DTG) plus 3TC do not have robust activity, or have no activity at all, against HBV. At the 2023 IDWeek and EACS meetings, a few important studies were presented about challenges healthcare professionals face for people living with HIV with positive anti-HBc and the implications for ART regimen selection.

I participated in one of the studies presented at EACS investigating the impact of anti-HBc positivity in people living with HIV undergoing switch to a 2-drug regimen consisting of DTG/3TC. In contrast to another study presented at IDWeek where investigators aimed to determine the risk of HBV reactivation when switching to an ART regimen that lacked activity against HBV, our study investigated the impact of anti-HBc positivity on HIV virologic suppression.

Our Study
We conducted a multicenter, retrospective cohort study of people living with HIV in Western Europe who were switched from a 3-drug regimen containing tenofovir disoproxil fumarate (TDF) to a 2-drug regimen of DTG/3TC. Participants were stratified to anti-HBc positive and negative subgroups. A comparative analysis between these groups was performed to determine differences in virologic suppression (categorized as HIV-1 RNA undetectable, HIV-1 RNA <20 copies/mL but not quantifiable, or HIV-1 RNA >20 but <200 copies/mL). We reviewed data available for 2 years before and 3 years after the switch to DTG/3TC.

Among the 267 total participants included, 76 were anti-HBc positive (28%). At the time of switch to DTG/3TC, there was no difference between groups in the percentage of participants with undetectable HIV-1 RNA (80.3% of anti-HBc positive vs 87.4% of anti-HBc negative; P = .15).

However, 12 months after the switch to DTG/3TC, there was a statistically significant reduction in the percentage of participants with undetectable HIV-1 RNA in those who were anti-HBc positive (69.3%) vs anti-HBc negative (87.5%; P = .004). Similarly, we observed an increase in the percentage of participants with detectable HIV-1 RNA in those with anti-HBc positivity (19.7% at time of switch vs 30.6% 12 months post switch). These differences were sustained at Weeks 24 and 36 post switch: almost one third of those with anti-HBc positivity were not suppressed at the end of the 36-month follow-up period.

In a multivariate analysis, we found that anti-HBc positivity in those switched to DTG/3TC had a 3-fold increased risk of failing to achieve virologic suppression (odds ratio: 3.07; 95% CI: 1.39-6.79). Among the variables we evaluated (including age, year of infection, nadir CD4+ cell count, and previous HIV virologic failure), this anti-HBc positivity was the only variable that was associated with achieving virologic suppression.

My Interpretation
What is a possible explanation for our findings? For people with positive anti-HBc, there is still possible HBV replication within hepatocytes. In this study, for those with positive anti-HBc who may have previously received tenofovir-containing ART regimens, there may have been better control of intrahepatic HBV replication. When switched to DTG/3TC, it is possible there was less control of HBV replication, which could affect control of HIV. The mechanism for this phenomenon is unclear, but it is possible that HBV could upregulate HIV-1 transcription through its HBx protein. Low-level HIV viremia is concerning given its possible impact on chronic inflammation and subsequent adverse outcomes such as cardiovascular or metabolic events.

Results from our study suggest that anti-HBc positivity might be considered prior to switching to a regimen that lacks HBV activity as an ART switch strategy. Considerations for anti-HBc positivity on ART regimen selection are currently not included in the EACS management guidelines. In my practice, the finding of anti-HBc positivity now gives me pause before switching to a 2-drug regimen, owing to concerns about viral suppression. Prospective studies are needed to confirm these findings and inform guideline updates.

Your thoughts?
Will you start to incorporate anti-HBc positivity as a decision point in your practice before switching ART? Leave a comment to join the discussion and visit our program page for additional coverage of IDWeek and EACS 2023.