Assessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected subjects initiating HBV-active antiretroviral therapy in Thailand

Background: Hepatic Flare (HF) after initiation of highly active antiretroviral therapy (HAART) in HIV-HBV coinfected individuals is well recognized but prospective data on predictors and subsequent outcome are limited. Methods: The Tenofovir in HIV-HBV coinfection study was a randomized clinical trial of HBV-active HAART including lamivudine and/or tenofovir in antiretroviral naive HIV-HBV individuals in Thailand. Results: Early HF (EHF) was defined as ALT > 5 x ULN during the first 12 weeks. EHF was observed in 8 (22%) of individuals at a median of 56 days. 6/8 EHF cases were asymptomatic and resolved with HAART continuation, however one subject with underlying cirrhosis died following rapid hepatic decompensation. EHF was significantly associated with higher baseline ALT (79 IU/L vs 36 IU/L non-EHF, p = 0.008) and HBV DNA (9.9 log(10) c/ml vs 8.4 log10 c/ml non EHF, p = 0.009), and subsequent serological change. HBeAg loss occurred in 75% of EHF cases versus 22% in non-EHF (p = 0.04), and HBsAg loss in 25% of EHF cases versus 4% of non-EHF (p = 0.053). Conclusion: EHF after HBV active HAART initiation was frequently observed in this population. Timing of EHF, association with elevated ALT and HBV DNA and high rate of seroconversion are all consistent with immune restoration as the likely underlying process.