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HBV and ART at IAS 2025
HBV Reactivation and ART, a Growing Concern: What Did We Learn at IAS 2025?

Released: August 15, 2025

Laura J. Waters
Laura J. Waters, FRCP, MD
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Key Takeaways
  • Historically, antiretroviral therapy (ART) regimens have included at least 1 hepatitis B virus (HBV)–active agent. Now the impact of HBV-inactive ART regimens on HBV reactivation and acquisition is a potential concern.
  • At IAS 2025, presenters discussed evidence from the MODERATO and IMPALA studies, which suggests that the risk of HBV reactivation after switching to a tenofovir-free ART regimen is low, but further investigation is needed.

Despite progress in hepatitis B virus (HBV) prevention, a high burden of HBV and HIV coinfection persists in the European region—approximately 7%, which is similar to the global rate of coinfection. 

And for much of the last 30 years, recommended antiretroviral therapy (ART) options have included at least 1 HBV-active nucleos(t)ide reverse transcriptase inhibitor: lamivudine (3TC) or emtricitabine (FTC) (low genetic barrier against HBV), and/or tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide (TAF) (high genetic barrier against HBV).

However, we have recently seen entirely HBV-inactive regimens entering ART guidelines, including dolutegravir (DTG)/rilpivirine (RPV), a daily oral single-tablet regimen, and injectable long-acting (LA) cabotegravir (CAB) plus rilpivirine (RPV), administered every 1 or 2 months. Considering the prevalence of HIV and HBV coinfection, the impact of HBV-inactive ART regimens on HBV reactivation and acquisition is a potential concern.

Insights From CROI 2025
To this end, a scoping review presented at CROI 2025 demonstrated a 1.6% HBV reactivation rate in people with past HBV who switched to HBV-inactive ART; although investigators noted that this rate was lower in people with detectable surface antibody (sAb) pre-ART switch, detectable sAb was not entirely protective. Overall, investigators concluded that the risk of HBV reactivation was low but present.

Insights From IAS
In addition, at IAS 2025, we saw results of 2 randomized trials of ART switch to regimens with low genetic barrier against HBV or entirely HBV-inactive ART in countries with high HBV prevalence.

The MODERATO trial, undertaken in West and Central Africa, randomized people living with virally suppressed HIV to either continue tenofovir/3TC/DTG or tenofovir/3TC/efavirenz (EFV), or to switch to a tenofovir-free, dual ART regimen consisting of either DTG/3TC or atazanavir (ATV)/ritonavir (RTV) plus 3TC. Overall, 7% of the screened population was excluded because of active HBV. Investigators reported that ART switch to tenofovir regimens was noninferior to continuation of tenofovir-containing, 3–drug regimens regarding HIV virologic outcomes at Week 96. Of note, no HBV reactivation events were recorded.

The IMPALA trial, which randomized people living with virally suppressed HIV to continue oral tenofovir/3TC/DTG (n = 269, of whom 81 demonstrated natural HBV immunity) or to switch to LA CAB plus RPV (n = 271, of whom 86 had evidence of natural HBV immunity). There were no HBV reactivations in either arm, but the trial excluded people with prior HBV infection without immunity and HBV testing was undertaken only if transaminitis was observed. Of importance, there were no incident cases of HBV among people receiving tenofovir-containing oral ART, but 1 receiving HBV-inactive LA CAB plus RPV. However, 61% of participants had no evidence of HBV immunity at study entry, and a retrospective analysis of HBV DNA in all samples is planned to assess for subclinical HBV reactivation.

In all, although MODERATO and IMPALA support the safety of tenofovir-free regimens in countries with high HBV prevalence, both trials excluded people with active HBV, and HBV testing may not be routinely available. For IMPALA in particular, which investigated an HBV-inactive strategy, retrospective testing will reveal whether any subclinical HBV reactivation occurred. Even if you work in a low HBV-prevalence region, changing migration patterns means that we all need to consider HBV management within HIV care. Ultimately, we need consensus as to how best monitor for HBV reactivation in clinical trials and how to incorporate HBV vaccination strategies into trial design. After all, new HBV acquisition is an avoidable event and should be prevented as best we can.

Your Thoughts
What do you find most challenging about managing HIV and HBV coinfection? Will these new data from IAS 2025 affect how you approach these challenges? Leave a comment to join the discussion!

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