Advances in treating drug-resistant hepatitis B virus in HIV-infected patients

Treatment of HIV infection with nucleos(t)ide analogs active against hepatitis B virus (HBV) highly improves hepatic outcomes in HIV-HBV coinfected patients, especially when tenofovir (TDF) is part of the antiviral regimen. Drug resistance has been the major drawback and must remain as the most important caveat when planning to treat dually or HIV and HBV independently in coinfected patients.

The use of lamivudine (LAM) as the only active anti-HBV agent should strongly be discouraged in HIV-HBV coinfected patients, although it might be considered for individuals with low serum HBV-DNA and in the absence of liver cirrhosis as an exception. In any other case drug resistance may cause any clinical benefit of this antiviral HBV therapy to disappear, and lead to cross-resistance with other antivirals and even occasionally select for HBV vaccine escape mutants. In cirrhotics, liver enzyme flares may be accompanied by life-threatening decompensation. Entecavir is generally not recommended as an anti-HBV agent in HIV-HBV coinfected patients given its low residual antiretroviral activity and potential for selection of resistance mutations in HIV. Adefovir is not active against HIV using HBV dosing and is no longer recommended as HBV therapy given its limited antiviral effect. Finally, telbivudine is not active against HIV, it is less potent than TDF against HBV and depicts low barrier to resistance and cross-resistance to LAM or emtricitabine.

The introduction of TDF has drastically reduced the clinical relevance of hepatitis B drug resistance in HIV-HBV coinfected individuals. The use of LAM as the only active anti-HBV agent should strongly be discouraged in this population.