![[The Network Logo]](http://www.atdn.org/networklogo.jpeg)
Hepatitis B Treatmentby Lei Chou The AASLD annual conference is the leading liver diseases conference in the United States, this year's 5-day meeting was held in San Francisco in October. After the approval of several HBV drugs in the last few years, this year's conference did not break any important new ground in our knowledge base of hepatitis B. This update will discuss some of the major findings. Tenofovir (Viread)Coming off its August FDA approval for the treatment of chronic HBV, researchers presented two-year data on their long-term study of tenofovir vs. adefovir switch to tenofovir in HBeAg negative (Study 102) and HBeAg positive (Study 103) patients. Both studies were sponsored by Gilead, the maker of tenofovir, and will extend out to eight years. The results continue to show the drug's potency and high drug resistance barrier. Study 102 enrolled 375 HBeAg negative people, 91% who started with tenofovir were able to reach undetectable viral load (HBV DNA < 69 IU/mL). Those who switched from adefovir to tenofovir after 72 weeks had comparable results at 89% undetectable. It is well know that people who have chronic HBeAg negative disease rarely are able to clear HBV surface antigen (HBsAg) on oral antivirals. The results did not show tenofovir is any different, as none of the people in study 102 had HBsAg loss. In Study 103, about 25% of HBeAg positive people had a HBeAg seroconversion, an important treatment outcome as people who seroconvert have a higher chance of being able to maintain undetectable viral load when they stop treatment. In addition, about 5% of people in both treatment arms had developed HBsAg antibodies, as close to a cure for chronic HBV as we currently can achieve. These critical indicators will be closely watched as these studies move forward. If extended treatment with tenofovir is able to increase the rate of HBeAg seroconversion and HBsAg loss, people who have chronic HBeAg positive might be able to have better guidelines on when they might safely stop treatment and maintain undetectable HBV viral load. Another major outcome of these tenofovir studies is the continuing surveillance of the development of drug resistance. Of the 5 of the 24 people who still have detectable virus after 96 weeks experienced viral breakthrough. According to researchers most were due to drug non-adherence. No tenofovir specific drug resistant mutations have been identified so far in these two studies. In light of the recent data on long-term tenofovir use and bone density loss, the investigators will be amending the study protocols to include a bone density component. This will be an important addition to our knowledge in tenofovir toxicity, both for HBV and HIV patients, as previous studies in HIV were unable to clearly draw conclusions about bone density effects of tenofovir due to complicating effects of HIV infection and aging. Study 102 and 103 have relatively young (44 and 34 years of age, respectively) and healthy volunteers with no HIV coinfection, the long-term bone density data will be able to yield a clearer picture on this ongoing concern.
|
| Entecavir (Baraclude)The other potent HBV drug that received FDA approval in 2005 was entecavir - which is not recommended for people coinfected with HIV due to the risk of HIV drug resistance - also had 5-year data from roll-over studies at this year's AASLD. Because more than 1/3 of the volunteers dropped out before year 5 for various reasons, the results were not comparable to the original study which ended after 48 weeks. Of those who rolled over into the new study (ETV 022-091), 94% of HBeAg positive people had undetectable viral load at year 5, and about 1/3 additional people were able to reach HBeAg seroconversion, showing that the drug can maintain its viral suppression potency in this subset of patients who had favorable initial responses in the original study. There are several caveats to this data: the dosage of entecavir was increased from 0.5 mg to 1 mg in the rollover study; patients were treatment naive with no cross-resistance issues (only 1 volunteer developed entecavir resistance at year 5); and the high number of drop outs likely included more people who did not respond to treatment initially, thereby causing the final data to appear more favorable. In the HBeAg negative study (ETV 027-091), people who had relapsed after stopping successful 1-year entecavir treatment were restarted with entecavir at a higher dose (1mg). 95% (54/57) volunteers were able to reach undetectable viral load after 3 years of retreatment. It should be noted that this group of patients had already been successfully treated with entecavir in the earlier study, perhaps explaining the high retreatment response rate. Combination Therapy, side effects, and drug resistanceCombination HBV therapy is currently recommended for people with cirrhosis, existing drug resistance mutation HBV, or HIV coinfection. Several studies looked at this particular population. One study enrolled 145 volunteers with lamivudine resistance and gave them adefovir plus lamivudine for 4 years. 81% of volunteers were able to reach undetectable viral load and minimal development of additional resistance mutations. However, increased drug toxicity is a major concern with long-term combination therapy, particularly in people with more advance liver disease. This study showed that 18% had developed renal impairment and arterial hypertension for each of these side-effects after 4 years. It should be noted that this group of volunteers included 70% of people with cirrhosis as well as post liver or kidney transplant recipients. People with liver cirrhosis are at higher risk of developing drug resistance. Another study looked at the use of combination therapy in this population to see if this strategy can forestall the development of HBV drug resistant mutations. 288 volunteers were treated for 48 weeks, and 6% of people in the adefovir/lamivudine combination arm developed drug resistance, compared with 18% in adefovir monotherapy arm and 57% in the lamivudine monotherapy arm, showing that combination therapy does provide a higher drug resistance barrier in this population of sicker patients. As our knowledge of chronic HBV disease progression and its treatment continue to advance, one major impediment that is abundantly clear at this year's AASLD is the large number of poster presentations that were unable to provide definitive data either due to the small trial size or an inadequate trail design. People living with chronic HBV need adequately powered and well designed trials to answer some critical questions in order to make sound treatment decisions based on clear evidence. The ongoing debates over when to start treatment, monotherapy or combinations, prevention of drug resistance, long-term treatment side effects, and the possibility of stopping treatment and maintaining viral suppression remain controversial. It is hoped that the newly established HBV clinical trials network at the NIDDK will start to address these important questions. This article is not a part of AASLD 2008, nor has it been approved by AASLD 2008.
|
|
Viread versus Hepsera for Hepatitis BA press release regarding the results of two studies comparing Hepsera to Viread in the treatment of Hepatitis B (HBV) The results of both studies (Studies 102 and 103), published in the December 4, 2008 issue of The New England Journal of Medicine (N Engl J Med 2008; 80-2878), show that Viread is significantly more effective in treating the virus that causes chronic hepatitis B than one of the most widely prescribed oral medications for HBV in the United States, Hepsera (adefovir dipivoxil), also developed and marketed by Gilead. Studies 102 and 103 compare Viread to Hepsera among patients with compensated liver disease and HBeAg-negative (presumed pre-core mutant) chronic hepatitis B and HBeAg-positive hepatitis B, respectively. Results demonstrate that at week 48, patients with chronic hepatitis B who received Viread experienced superior efficacy results compared to those who received Hepsera, as shown by the significantly higher percentage of Viread patients in each trial achieving the primary efficacy endpoint. Data also indicate that at week 48, Viread was superior to Hepsera in reducing HBV DNA levels to below 400 copies/mL and was comparable to Hepsera in achieving histological response.  Jack Waters is a long time friend and serves on the Board of Directors of The Network. He even started a Facebook Cause for The Network. New York Case ManagementFor HIV+ people - insured or not insured or barely insured or having trouble with co-payments or accessing what you need because you're broke. No fee, charge or insurance required. Apply for ADAP, ADAP Plus, APIC, Medicaid, Sustainable Living Fund and other programs for HIV-positive New Yorkers. E-mail us at The Network, or call our toll-free number at (800) 734-7104 for help getting treatment or co-payment assistance, housing relief, insurance or benefits assistance, health care, living expenses, food, dealing with hepatitis co-infection, legal referrals and counseling. HIV+ people anywhere in the New York City area welcome to join. |