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The guanosine analogue entecavir effectively inhibits hepatitis B virus (HBV) replication. In a previous study, entecavir did not appear to inhibit HIV replication at concentrations achieved in vivo, and several treatment guidelines have recommended using the drug in coinfected patients who need HBV therapy but do not yet require treatment for HIV infection. Now, a detailed analysis of entecavir’s effects on HIV replication in coinfected patients suggests that this recommendation should be reconsidered.
Three HIV/HBV-coinfected patients who were not on antiretroviral therapy received entecavir for chronic HBV infection. In all three individuals, HBV DNA levels fell sharply, as expected; surprisingly, HIV RNA levels also declined by approximately 1 log10. Using a novel phenotypic assay, the investigators demonstrated that at clinically relevant concentrations, entecavir partially inhibits HIV replication. While on entecavir, one patient had emergence of HIV harboring the M184V mutation, which confers high-level resistance to the anti-HIV drugs lamivudine and emtricitabine. In vitro studies showed that M184V variants derived from this patient were also resistant to entecavir.
McMahon MA et al. The HBV drug entecavir — Effects on HIV-1 replication and resistance. N Engl J Med 2007 Jun 21; 356:2614-21.
Hirsch MS. Entecavir surprise. N Engl J Med 2007 Jun 21; 356:2641-3.
Comment
Results from this small but influential study suggest that the HBV drug entecavir may partially inhibit HIV replication and select for virus with the M184V resistance mutation. Based on these findings, the Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents no longer recommends using entecavir to treat HBV in coinfected patients unless they are also receiving effective HIV treatment. An important “take-home” lesson is that new agents for HBV should be carefully studied in HIV-coinfected patients to determine the optimal treatment of both viral infections.