HBV reactivation after switching to cabotegravir plus rilpivirine therapy among people living with HIV: do not forget the reservoir

In 2022, the WHO estimated that 254 million people were living with chronic HBV infection. Among these individuals, approximately 2.7 million were also living with HIV (PWH).1 Current ART strategies are increasingly focused on reducing overall drug exposure to minimize potential long-term toxicities. Simplification of therapeutic strategies such as dual therapy or long-acting (LA) regimens also allows people to improve their quality of life.2 However, withdrawal of antiretrovirals with dual anti-HBV and anti-HIV activity such as tenofovir disoproxil fumarate or tenofovir alafenamide, lamivudine or emtricitabine from ART regimens in coinfected individuals exposes them to an increased risk of HBV reactivation. We report a case of HBV reactivation in a PWH and with isolated anti-HBc seropositivity following simplification to LA ART. A 47-year-old man of sub-Saharan origin, employed as a warehouse worker, was diagnosed with HIV-1 infection in 2004 (CDC stage A3). At that time, serological testing revealed evidence of resolved HBV infection, with isolated anti-HBc antibodies. ART with tenofovir disoproxil fumarate, emtricitabine and efavirenz was initiated the same year. HIV replication was well controlled until 2012, when the patient discontinued ART for 5 years. In 2017, HIV viral load was 5.5 log10 copies/mL and the nadir CD4 cell count was 7.2 cells/mm3, when he resumed ART with abacavir, lamivudine and dolutegravir. The serological profile showed the presence of isolated anti-HBc antibodies. No HBV DNA was measured at the time of ART re-initiation. HIV genotyping did not detect any antiretroviral resistance mutations, and the viral load was 1000 mIU/mL.12 Guidelines are increasingly incorporating the use of HEPLISAV-B into their recommendations.3 This vaccine is authorized in many regions (the USA, the EU, Great Britain), but its commercialization outside the USA needs to be further developed, for example in the EU. This case of reactivation highlights the need to improve and harmonize the management of PWH presenting anti-HBc antibodies in order to prevent future cases of reactivation. Several cases and small series have recently been reported following the switch to a cabotegravir/rilpivirine injectable regimen.13–16 The risk of HBV reactivation in patients with an isolated HBc serological profile appears to be low in this context, particularly when anti-HBs antibodies are present. The risk appears to be higher in individuals with recent HBsAg seropositivity17 or low CD4 nadir count,18 and HBV reactivation after the withdrawal of an anti-HBV/HIV drug can lead to very serious complications, as already reported.19 In conclusion, the risk of HBV reactivation in PWH with isolated anti-HBc seropositivity should not be overlooked. Switching to ART without agents active against HBV must be done with caution, depending on the patient's profile, and should be closely monitored. This work was supported by the Agence Nationale de Recherches sur le SIDA et les hépatites virales|Maladies Infectieuses Emergentes (ANRS|MIE). A.F. has reported presentation fees from Gilead, ViiV Healthcare and MSD. E.T. has reported travel grants from Gilead and ViiV Healthcare and consultancy for Gilead, Abbvie and ViiV Healthcare. G.P. has received travel grants, consultancy fees and honoraria from Gilead Sciences, ViiV Healthcare, Merck and Takeda. R.P. has received travel grants and advisory fees from Gilead, ViiV Healthcare and Merck. V.C. has received travel grants, research funding and advisor’s honoraria from Gilead, ViiV Healthcare, MSD and Moderna. V.P. has received travel grants and advisor’s honoraria from Gilead, ViiV Healthcare and MSD. All other authors: none to declare.