Tenofovir (Viread) is an effective and safe treatment for chronic hepatitis B virus monoinfection, according to two studies due to be presented to 43rd Annual Meeting of the European Association for the study of the Liver in Milan on April 25th.
After 72 weeks, the majority of hepatitis B `e` antigen-negative and hepatitis B `e` antigen-positive patients achieved a hepatitis B viral load below 400 copies/ml. Few patients experienced clinical or laboratory side-effects, and there was no evidence that treatment with the drug caused kidney problems.
Tenofovir is a nucleotide reverse transcriptase inhibitor and is a preferred drug for first-line anti-HIV therapy. The drug also has activity against hepatitis B virus and received scientific approval in Europe as a treatment for hepatitis B monoinfection.
Tenofovir is already recommended as a component of first-line antiretroviral therapy in people coinfected with HIV and hepatitis B due to its activity against hepatitis B.
The manufacturers of tenofovir, Gilead, designed two separate studies to test the safety and efficacy of tenofovir in patients with hepatitis B monoinfection.
Tenofovir in hepatitis B virus `e` antigen-negative patients
The first study, Study 102, included 375 patients with chronic hepatitis B virus infection who were `e` antigen-negative (presumed precore mutant). The study included patients who were starting anti-hepatitis B therapy for the first time, as well as patients who had previously received treatment with 3TC (lamivudine), another antiretroviral drug which works against hepatitis B virus.
Patients were randomised on a two to one basis to receive either tenofovir (300mg, once-daily) or adefovir (10mg, once-daily). After 48 weeks, all eligible adefovir-treated patients were switched to tenofovir.
After 72 weeks of treatment, 91% of patients originally randomised to receive tenofovir had a hepatitis B viral load below 400 copies/ml. Of the adefovir-treated patients who switched to tenofovir after 48 weeks, 88% had a viral load below 400 copies/ml by week 72 of the study. All the adefovir treated patients who had a viral load below 400 copies/ml at week 48 maintained a viral load below this level after switching to tenofovir. Furthermore, of the adefovir-treated patients with a viral load above 400 copies/ml at the time of switch to tenofovir, 94% had a viral load below this level by week 72.
Normal ALT levels at week 72 were observed in 79% of patients who initiated with tenofovir and 77% of patients who switched to this drug from adefovir.
Serious side-effects were equally rare (below 1%) in both the tenofovir- and adefovir-initiating patients. Grade 3/4 laboratory abnormalities were seen in approximately 14% of patients in both arms of the study. Tenofovir was not associated with kidney problems (creatinine clearance below 50ml/minute).
Tenofovir for hepatitis B virus in `e` antigen-positive patients
The second study involved 266 patients with chronic hepatitis B virus who were hepatitis B virus `e` antigen-positive. All were taking hepatitis B virus for the first time. Once again, patients were randomised on a two to one basis to take either tenofovir (300mg once-daily) or adefovir (10mg once-daily) for 48 weeks, with the adefovir-treated patients then switched to tenofovir.
At week 72, 79% of the patients who started therapy with tenofovir had a hepatitis B viral load below 400 copies/ml, as did 76% of patients who initiated treatment with adefovir before switching to tenofovir.
All the patients who started treatment with adefovir and had a viral load below 400 copies/ml maintained a viral load below this level after switching to tenofovir. Furthermore, 72% of adefovir-treated patients who switched to tenofovir with a viral load above 400 copies/ml had a viral load below this level by week 72 of the study.
Normal ALTs were observed in 77% of patients who started treatment with tenofovir at week 72 and in 61% of those switching to tenofovir from adefovir.
At week 64, 26% of patients who originally received tenofovir seroconverted and became e antigen negative, as did 21% of patients who initiated therapy with adefovir. In addition, 5% of patients in the tenofovir arm experienced loss of “s” antigen, indicating clearance of hepatitis B infection.
Serious side-effects were observed by week 72 in 4% of the tenofovir arm and 7% of the patients who switched from adefovir. Similar proportions of patients in both study groups (12% vs. 11%) had grade 3/4 laboratory abnormalities. No patient had creatinine clearance below 50 ml/minute.
“These 72-week data indicate that Viread has the potential to produce a significant and sustained effect on hepatitis B virus DNA suppression”, said Dr Patrick Mercellin of Hopital Beaujou, University of Paris, who added, “I believe Viread will be an important new treatment option for patients living with chronic hepatitis B.”