Case Presentation: A 67 year old African American male with history of chronic hepatitis B virus (HBV) infection on entecavir therapy [HBV viral load (VL)=64 copies/ml] since 2013 was hospitalized for evaluation of six week history of generalized weakness, thirty pound weight loss and progressive dyspnea. Physical exam was significant for decreased breath sounds and dullness on percussion at the right base. Admission chest radiograph revealed a right-sided pleural effusion demonstrating lymphocyte predominant exudative characteristics following diagnostic thoracentesis. Serum cryptococcal antigen was positive and pleural fluid fungal cultures grew Cryptococcus neoformans. The patient had no revealed history of immunosuppressive conditions or medication exposures, but review of electronic medical record demonstrated a positive human immunodeficiency virus type 1 (HIV-1) antibody initially collected in April 2017 (four years after entecavir was initiated). The patient was aware of his HIV diagnosis and was treatment-naive but had withheld this history from admitting and outpatient hepatology care providers. An absolute CD4 count (78 cells/mm3) and HIV-1 VL (58,115 copies/mL) confirmed acquired immunodeficiency syndrome and poor viral control. An HIV genotype revealed an M184V gene mutation with predicted resistance to lamivudine and emtricitabine. At discharge, patient received fluconazole for isolated cryptococcal parapneumonic effusion, entecavir was continued, and infectious disease follow-up arranged to initiate highly active antiretroviral therapy (HAART).
Discussion: Entecavir is a guanosine nucleoside analogue FDA approved for the treatment of chronic HBV infection. Entecavir is phosphorylated intracellularly to its active triphosphate form inhibiting HBV viral synthesis via DNA polymerase. Entecavir was originally thought to have little effect on HIV-1 replication at clinically relevant doses. In fact, several previous treatment guidelines recommended entecavir for hepatitis B treatment in HIV-1 infected persons who did not meet criteria for antiretroviral initiation. However, more recent studies have demonstrated entecavir to be a potent partial inhibitor of HIV-1 replication in vitro and in vivo with approximately 1-log10 VL reductions in HIV-1 RNA. Moreover, it can select for the M184V mutation conferring high-level resistance to extensively used nucleoside reverse transcriptase inhibitors (NRTI), lamivudine and emtricitabine, as was seen in this case. Given this potential for development of NRTI resistance, entecavir is no longer recommended for patients co-infected with HIV and HBV who are not receiving HAART. Current HBV treatment guidelines recommend screening for HIV prior to initiation of antiviral therapy and coordinating treatment for dual infected patients.
Conclusions: Initiation of anti-viral medications in chronic HBV infected patients co-infected with HIV may have significant implications in the development of anti-retroviral resistance limiting lifetime therapeutic options. As the initial diagnosis of HBV and HIV is often made during acute hospital admissions, hospitalists play an important role in ensuring chronic HBV practice guidelines are observed which includes screening for HIV prior to starting HBV therapy.
To cite this abstract:Fulco, F; Sindel, AD. Entecavir Induced Antiretroviral Resistance. Abstract published at Hospital Medicine 2018; April 8-11; Orlando, Fla. Abstract 580. https://www.shmabstracts.com/abstract/entecavir-induced-antiretroviral-resistance/. Accessed December 11, 2019.