Tenofovir plus Emtricitabine or Lamivudine Does Not Always Suppress Hepatitis B in HIV/HBV Coinfected


HIV/HBV coinfected people with high hepatitis B virus (HBV) levels and those who are HBeAg positive are at greater risk of not achieving HBV suppression after a year on tenofovir plus emtricitabine or lamivudine, but most did so eventually, researchers reported in the February 21, 2013, advance online edition of AIDS.

A few drugs -- including tenofovir (Viread), emtricitabine (FTC or Emtriva, or with tenofovir in the Truvada coformulation), and lamivudine (3TC or Epivir) -- are dually active against both HIV and HBV. Treatment guidelines recommend that people coinfected with both viruses should include at least one dually-active agent in their antiretroviral regimen.

Kate Childs from King’s College London and colleagues conducted a study to identify and characterize people who continued to have detectable HBV DNA but undetectable HIV RNA after 48 weeks on tenofovir plus either emtricitabine or lamivudine. Emtricitabine and lamivudine are chemically similar drugs with generally equivalent efficacy and prone to cross-resistance.

This case-control study -- which recruited participants from the King’s College Hospital Institute of Liver Studies coinfection clinic -- included 23 delayed responder case patients, defined as having detectable HBV DNA (>20  IU/ml) and undetectable HIV RNA (< 40 copies/mL) after 48 weeks on combination therapy. They were compared with 24 control patients who had both undetectable HIV and HBV after 48 weeks.

Most participants (about 72%) were of black African ethnicity and the median age was 43 years; 91% of delayed responders and 71% of control patients were men. About half were hepatitis B "e" antigen (HBeAg) positive. Delayed responders had a longer average duration of HIV infection (4 vs 2 years) and a trend toward a lower median CD4 cell count (72 vs 192 cells/mm3) compared with concordant responders; 90% were on antiretroviral therapy, almost all including dually-active drugs.


  • 87% of the delayed responders were HBeAg positive compared with just 46% of control subjects, a statistically significance difference.
  • 9 of the 23 delayed responders (39%) and 7 of the 24 control subjects (29%) had received lamivudine monotherapy -- a drug with a relatively low barrier to resistance -- prior to starting tenofovir.
  • However, similar proportions of delayed responders and control patients had lamivudine or emtricitabine resistance before taking tenofovir (30% vs 24%, not a significance difference).
  • Delayed responder case patients had significantly higher baseline HBV DNA prior to starting lamivudine and tenofovir.
  • Shorter duration of ART and CD4 cell count < 200 cells/mm3 were also risk factors for detectable HBV DNA.
  • 16 of the 23 case patients (70%) eventually achieved undetectable HBV DNA, after 42 months on average.
  • However, 6 delayed responders (26%) still had detectable HBV DNA after 46 months of follow-up.
  • Although delayed responders maintained low-level HBV viremia for a prolonged period, this did not lead to drug resistance.
  • Only 1 delayed responder developed a new lamivudine/emtricitabine resistance mutation; this patient's HBV DNA became undetectable 4 months after adding another hepatitis B drug, entecavir (Baraclude).
  • No participants in either group developed tenofovir resistance mutations.

"We report the largest series of HIV/HBV coinfected patients failing to achieve undetectable HBV after 48 weeks on [tenofovir plus emtricitabine or lamivudine] despite undetectable HIV viremia," the study authors wrote.

"This outcome was associated with positive [HBeAg] and higher baseline HBV DNA," they added, as has also been observed in prior studies of HBV monoinfected (HIV negative) people.

"Therapy with [tenofovir plus emtricitabine or lamivudine]is indeed superior to [tenofovir] monotherapy," they concluded. "Our findings indicate that intensification of HBV treatment with entecavir in the absence of viral rebound or the development of new [lamivudine/emtricitabine] resistance mutations is not necessary."

"Combination therapy with [tenofovir] and [lamivudine/emtricitabine] increases the likelihood of sustained HBV DNA suppression," they elaborated in their discussion. "More advanced immunodeficiency and suboptimal compliance with the anti-HBV regimen decreased the likelihood of a sustained response in HIV-HBV coinfected subjects."2/28/13


K Childs, D Joshi, R Byrne, et al. Tenofovir based combination therapy for HIV/HBV co-infection: Factors associated with a partial HBV Virological response in patients with undetectable HIV viraemia. AIDS. February 21, 2013 (Epub ahead of print).