HBsAg seroreversion in HBsAg-negative/HBcAb-positive patients with HIV infection treated with direct-acting antivirals for HCV: A retrospective study

No data on the risk of HBV reactivation in HCV-HIV co-infected patients undergoing DAAs have been published yet. According to international guidelines , all HIV-infected and HBsAg-positive patients should be treated with antiretroviral therapy (ART) containing nucleoside reverse transcriptase inhibitors (NRTI) dually active against HBV and HIV, such as tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) plus lamivudine (3TC) or emtricitabine (FTC), with consequent no risk for HBV reactivation. However, there are not precise indications regarding HBsAg-negative and HBcAb-positive individuals with HIV infection (4.7%–12% of HIV population in Europe). To date, the risk of HBsAg seroreversion in HCV-HIV co-infected patients with HBsAg-negative and HBcAb-positive serology, treated with NRTI-sparing ARV regimens, and exposed to DAAs regimen, is not known. The authors retrospectively included all the HCV-HIV co-infected and HBsAg-negative/anti-HBc positive individuals, who started DAAs from October 2014 to September 2017 in Bologna. Since HBV DNA levels were not routinely measured at DAAs initiation, patients with undetectable or low HBV DNA viral load (VL) were indiscriminately included. the authors enrolled in the study 24 subjects, who met inclusion criteria. Two out of 24 patients (8.3%) developed HBsAg seroreversion during the observation period. Nowadays, DAAs regimens are widely used also among patients with HIV or with HBV coinfection. In the latter group, a risk of HBV reactivation has been reported of 21% in HBsAg positive and a risk of HBsAg seroreversion of 0.5% in HBsAg negative/HBcAb positive patients (all HIV-uninfected) treated with DAAs, by a recent metanalysis. In this study, the authors observed an unexpectedly high rate of 8% of HBsAg seroreversion among HCV-HIV co-infected subjects with HBsAg-negative/HBcAb-positive status.To our knowledge, this is the first study analyzing the risk for HBsAg seroreversion in HCV-HIV patients with isolated positive HBcAb serology who undergo DAA-regimens and receiving NRTI-sparing regimen for HIV. Such a high seroreversion rate (8.3%) was not reported before among patients with the same characteristics, but HIV-negative. Our findings suggest that low CD4+-T cells nadir and history of AIDS might be potential risk factors for HBsAg seroreversion. Subjects with low CD4+-T cells nadir generally have a more compromised immune system even after they achieve good immunovirological control. In conclusion, the results of this study suggest that people with HIV and HBsAg-negative/HBcAb-positive status receiving a NRTI-sparing ART might be at “high risk” for HBsAg seroreversion when treated with DAAs. Therefore, from our data one could recommend ART containing TDF, TAF, 3TC or FTC during DAAs treatment to prevent this potentially life-threatening event.