Although lamivudine (3TC, Epivir) has potent activity against hepatitis B virus (HBV), patients who have chronic HBV and HIV infection who are treated with lamivudine-containing regimens often develop resistance to the lamivudine. As a result, there is tremendous interest in whether the use of a second anti-HBV agent -- specifically tenofovir (TDF, Viread) -- can augment anti-HBV responses and reduce the incidence of lamivudine resistance.

Using data from the Gilead 903 study comparing tenofovir with stavudine (d4T, Zerit) -- both in conjunction with lamivudine and efavirenz (EFV, Sustiva, Stocrin) -- investigators retrospectively evaluated patients from the study who were positive for HBV surface antigen and had detectable HBV viremia at a baseline level of >1 million copies. Hepatitis C-infected patients were excluded from the analysis.

Five and 6 patients met these criteria from the tenofovir and stavudine groups, respectively. Based on the study design, the tenofovir group received 2 active HBV drugs (tenofovir and lamivudine), while the stavudine group received only one (lamivudine). At the end of 44 weeks, those assigned to the tenofovir and lamivudine arm showed a 4.5-log reduction in HBV DNA, compared with 1.9 log for those who received only lamivudine. In addition, the alanine transaminase level declined by 53 IU/L in the tenofovir/lamivudine arm, compared with an increase of 24 IU/L in the lamivudine-only arm, and lamivudine resistance occurred in 1 and 5 patients, respectively.

This small dataset provides strong evidence that in the treatment of HBV infection, as with HIV, 2 drugs are better than one, resulting in greater reductions in viral load and lower rates of resistance. For people with HIV who have detectable HBV viremia, combination therapy with tenofovir and lamivudine (or emtricitabine [FTC, Emtriva]) is likely to become the standard of care.