Adefovir appears to be effective against 3TC-resistant hepatitis B (HBV) in people coinfected with HIV and HBV, according to the results of a clinical trial presented to the Annual Meeting of the European Association for the Study of the Liver (EASL), in Madrid last week. Other studies presented to the conference, between 18-19 April, indicated adefovir was effective against 3TC-resistant HBV in patients infected with only HBV and that the drug was associated with improved liver function in people with precore mutant chronic HBV, which is associated with rapid progression to liver disease.
In a multi-centre, open label study, 35 patients coinfected with HIV and HBV, with an undetectable HIV viral load and proven 3TC-resistant HBV were given 10mg adefovir once daily. After 92 weeks of treatment significant decreases in HBV viral load were observed across the study group, with an average fall in serum HBV DNA of 5 logs. An undetectable HBV viral load (below 1,000 copies/mL) was seen in 29% of the study participants.
No adefovir resistance mutations emerged in the course of the trial and 9% of the study participants became HBV antigen-negative by the end of the study. Adefovir was well tolerated, and although four people discontinued treatment because of side effects, trial investigators did not believe that this was associated with adefovir.
Another study presented at the EASL meeting demonstrated the effectiveness of adefovir in people only infected with HBV and who have a 3TC-resistant strain of the virus. In an ongoing 48 week double-blind placebo controlled trial, 59 patients were randomised to receive either adefovir monotherapy, adefovir and 3TC in combination or 3TC monotherapy. Sixteen week data presented to the meeting showed that people in both the adefovir monotherapy and combination arms achieved a similar reduction in HBV viral load. However, HBV viral load remained unchanged in the 3TC arm. After 32 weeks, 32% of those receiving adefovir montherapy had seen their HBV lose its resistance to 3TC and revert to wild-type. Nobody in the 3TC arm achieved this.
Adefovir also appears to be effective against precore mutant HBV, which is associated with rapid progression to liver disease. In a 48 week double-blind placebo controlled trial, involving 185 people with precore mutant HBV and impaired liver function, patients were randomised to receive either 10mg of adefovir once daily or a placebo for 48 weeks. Liver biopsies showed that at the conclusion of the study, patients receiving adefovir were almost twice as likely (64% against 33%) to have improved liver function than those receiving the placebo. An undetectable HBV viral load (below 400 copies m/L) was achieved by 51% of those taking adefovir and nobody receiving the placebo. Similar side-effects were reported in both groups, which shared a 2% discontinuation rate.
Manufacturers of adefovir, Gilead Sciences, has applied for marketing approval for the drug in the USA, and is offering an expanded access scheme to make the drug available before marketing approval is granted. People with 3TC-resistant HBV will qualify for the scheme in the USA, European Union and Australia.