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Tenofovir Replacing AZT of ABC, Keeping 3TC, Suppresses HBV DNA
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52nd ICAAC, September 9-12, 2012, San Francisco
Mark Mascolini
Replacing zidovudine (AZT) or abacavir (ABC) with tenofovir while maintaining lamivudine (3TC) in an antiretroviral regimen made HBV DNA undetectable in almost 90% of HBV/HIV-coinfected patients in Taiwan [1]. Only one person had to stop tenofovir, because of impaired renal function at treatment week 36.
HBV infection is hyperendemic in Taiwan, where for many years 3TC was the only anti-HBV drug used in antiretroviral regimens. As a result, resistance to 3TC often emerged. Researchers from National Taiwan University Hospital in Taipei planned this study to gauge clinical and virologic responses to replacing AZT or ABC in such regimens with tenofovir and maintaining 3TC.
The study focused on 30 HBV/HIV-coinfected people seen between November 2010 and August 2012. All were taking 3TC with ABC or AZT and had a YIDD or YVDD mutation conferring resistance to 3TC. No one had taken any other agents active against HBV. The researchers measured HBV DNA and HBsAg titer 4, 8, 12, 24, 36, and 48 weeks after the switch to tenofovir. They also measured AST, ALT, and total bilirubin every 12 weeks and HBeAg and anti-HBe at week 48.
Median age stood at 44 years in the 30 study participants (range 27 to 65), 29 (97%) were men, and 26 (87%) had HBV genotype B. Median duration of 3TC use was 6.1 years (range 1.0 to 14.2) and median duration of 3TC resistance 2.1 years (range 0.7 to 14.2). Median HBV DNA measured 6.5 log10 copies/mL at the switch to tenofovir (range 2.9 to 9.1), and 21 people (70%) had an HBV load above 100,000 copies.
When switching to tenofovir, 4 study participants (13%) had an AST or ALT more than 2 times the upper limit of normal, 6 (20%) had a hepatitis flare in the year before the study, and 1 had chronic HCV infection. Sex between men was the HIV transmission route in 23 participants (77%); no one reported injection drug use as a transmission risk. Median CD4 count at the switch to tenofovir was 481 (range 37 to 1879), and median HIV load 1.6 log10 copies/mL (under 50 copies, range 1.6 to 4.7).
Follow-up on the 30 enrolled patients averaged 44 weeks. At weeks 4, 8, 12, 24, 36, and 48, data were available from 25, 24, 24, 28, 25, and 22 patients. At those points median declines in HBV DNA were 2.2, 3.0, 2.9, 3.8, 4.4, and 4.8 log10 copies/mL. At the same points proportions of people with undetectable HBV DNA (below 128 copies) were 16.7%, 30%, 36.7%, 43.3%, 53.6%, and 87.0%.
One of 11 people tested had HBeAg seroconversion. Median changes in HBsAg titer from baseline at weeks 4, 8, 12, 24, and 48 were -0.1, -0.2, -0.2, -0.1, and -0.2 log10 IU/mL. There was 1 hepatitis flare due to acute HCV infection.
The researchers conclude that adding tenofovir to a regimen containing 3TC in HBV/HIV-coinfected people is highly effective in suppressing HBV replication and treating 3TC-resistant virus.
US guidelines emphasize that 3TC or emtricitabine (FTC) should not be the only anti-HBV drugs in an antiretroviral regimen prescribed for HBV-coinfected people [2]. They caution that "patients who have HIV/HBV coinfection may be at risk of acute exacerbation of hepatitis after initiation or upon discontinuation of TDF, 3TC, or FTC," so patients starting or stopping these drugs should "should be monitored closely for clinical or chemical hepatitis."
References
1. Lee K, Chang S, Su Y, et al. clinical and virologic outcomes after switch to tenofovir/lamivudine of HIV-infected patients with hepatitis B virus (HBV) resistance to lamivudine in an hyperendemic area for HBV infection. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-218.
2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. 1-239. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
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