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ICAAC 2012: Switching to Tenofovir in ART Regimen Suppresses Hepatitis B in HIV/HBV Coinfected

HIV/HBV coinfected people who substituted tenofovir DF (Viread) for zidovudine (AZT; Retrovir) or abacavir (Ziagen) in their antiretroviral regimen saw a reduction in hepatitis B viral load, despite HBV resistance to lamivudine (3TC; Epivir), according to a poster presentation at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this week in San Francisco.

Some antiretroviral drugs used to treat HIV are also active against hepatitis B virus (HBV), including tenofovir, lamivudine, and the related compound emtricitabine (Emtriva). Current DHHS antiretroviral treatment guidelines recommend that HIV/HBV coinfected people should include at least 1 of these drugs in their HIV regimen. HBV rapidly develops resistance to lamivudine, however, which could compromise treatment effectiveness.

Kuan-Yeh Lee, MD, and colleagues from National Taiwan University Hospital in Taipei prospectively evaluated clinical and virological responses to combination antiretroviral therapy (ART) when HIV/HBV coinfected patients switched from zidovudine or abacavir -- neither of which have anti-HBV activity -- to tenofovir.

Between November 2010 and August 2012, researchers enrolled 30 coinfected patients with known resistance to lamivudine. At study entry, all had been taking ART regimens with lamivudine as their only drug with anti-HBV activity.

Almost all participants were men and the average age was 44 years; about three-quarters reported sex with men as their main HBV risk factor. They had well-preserved immune function, with a median CD4 T-cell count of 481 cells/mm³, and the median HIV viral load was < 50 copies/mL.

Most (87%) had HBV genotype B, approximately one-half were hepatitis B "e" antigen (HBeAg) positive, and the mean baseline HBV DNA level was 6.5 log copies/mL; 1 person was triply infected with hepatitis C. The average duration of lamivudine use was about 6 years and the average period of resistance was about 2 years.

The researchers measured HBV DNA viral load and hepatitis B surface antigen (HBsAg) levels at baseline and at weeks 4, 8, 12, 24, 36, and 48 after switching drugs. They also periodically assessed HBV drug-resistance mutations (YM/I/VDD), liver transaminase levels, and serum creatinine (a potential marker of kidney toxicity).

Results

• After an average follow-up period of 44 weeks, median changes in HBV viral load were -2.2 logcopies/mL at week 4, -3.0 at week 8, -2.9 at week 12, -3.8 at week 24, -4.4 at week 36, and -48 logcopies/mL at week 48.
• The proportion of patients achieving undetectable HBV DNA (<128 copies/ml) at these time points were 16.7%, 30.0%, 36.7%, 43.3%, 53.6%, and 87.0%, respectively.
• Only 1 out of 11 tested patients (9.1%) experienced HBeAg seroconversion.
• Changes in HBsAg levels were "negligible" across time.
• 1 patient experienced acute hepatitis due to new hepatitis C virus infection.
• No other study participants experienced liver enzyme flares after switching therapy.

After 48 weeks of follow-up, switching to tenofovir/lamivudine in HIV/HBV coinfected patients with HBV resistance to lamivudine "was highly effective in achieving suppression of HBV replication," the researchers concluded. In contrast, they added, "HBsAg titres did not decline after [the] switch."

9/14/12

Reference

K Lee, S Chang, Y Su, 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 Antimicrobial Agents and Chemotherapy. San Francisco. September 9-12, 2012. Abstract H-218.