Background
HBV reactivation in people living with HIV and evidence of past HBV infection is an important consideration when evaluating the risk/benefit of discontinuing HBV-active ART in favor of other treatment regimens. We aimed to summarize available evidence on reactivation risk after switching to HBV-inactive regimens, and to identify predictors that may guide clinical practice.
Methods
We searched electronic databases (PubMed, Embase, 1996-2024) and conference abstracts (2021-2024) for studies and case reports describing HBV reactivation in treated people switching to tenofovir-free ART. Reactivation was defined as HBsAg and/or HBV DNA detection by routine diagnostic assays in individuals who tested HBsAg negative and anti-HBc positive pre-switch. Reactivation in the context of ART interruption was excluded.
Results
We identified 7 studies and 8 case reports. Pre- and post-switch HBV investigations were variable in routine care. Studies reported 133 reactivations among 11731 switches (1.1%), with two US cohorts contributing most data; 2854/11731 allowed post-switch use of 3TC/FTC and only one reported accordingly, noting no reactivations over 144 weeks among 71 people on DTG/3TC. There were 99 reactivations among 6093 switches to HBV-inactive ART (1.6%), with proportions ranging from 1.5% to 10% across studies (Table 1). In studies and case reports, the earliest detection of HBsAg and/or HBV DNA ranged from 1 month to 14 months post-switch. Reactivations were typically less commonly with pre-switch anti-HBs ≥10 IU/L (range 0-11%) compared with lack or loss of anti-HBs (3.2-14%). Reactivations occurred across a wide range of CD4 counts and HIV viral loads. The risk was higher with HIV viremia, lower CD4 counts, nadir CD4 counts <100 cells/mm3, and HBV DNA detection by ultrasensitive PCR pre-switch. Reactivations were variably associated with ALT increases. Acute hepatic flares typically resolved after re-introduction of HBV-active agents, with HBsAg and/or HBV DNA loss documented within 2-5 months.
Conclusions
Moderate-to-low quality evidence indicates that HBV-inactive ART carries a low but notable risk of HBV reactivation in people with a past HBV infection. Risk factors include lack or loss of anti-HBs, low current or nadir CD4 counts and detectable HBV DNA pre-switch, while detection of HBsAg and/or HBV DNA post-switch signals a heightened risk of hepatic flares. Standardization of pre- and post-switch HBV monitoring practices remains a critical need.
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