Background

Hepatitis B virus (HBV) infection increasingly is a cause of illness and death in patients coinfected with HIV. The nucleotide analogue tenofovir, commonly used in combination therapy for HIV infection, is known to have activity against HBV. Although tenofovir frequently is used in patients with HIV/HBV coinfection, its efficacy in the treatment of HBV in HIV-coinfected patients had not been studied previously in randomized controlled trials.

Tenofovir Not Inferior to Adefovir

Abstract: Tenofovir Disoproxil Fumarate Is Not Inferior to Adefovir Dipivoxil for the Treatment of Hepatitis B Virus in Subjects Who Are Co-infected with HIV: Results of ACTG A5127. Marion Peters, J Anderson, P Lynch, J Jacobson, K Sherman, B Alston Smith, S Swindells, T Liu, V Johnson, R Pollard, J Rooney, B Polsky, and AACTG 5127 team. Abstract 124.

Description: A double-blind, placebo-controlled trial, ACTG A5127, compared the efficacy and safety of tenofovir and adefovir for the treatment of HBV in HIV-infected patients on stable antiretroviral therapy. Patients were required to have HBV DNA >=100,000 copies/mL and compensated liver disease, and were randomized to receive tenofovir 300 mg daily or adefovir 10 mg daily. The study was designed as a noninferiority study, with the primary endpoint of time-weighted average change in HBV DNA from baseline to week 48.

Patients were exposed to combination ART for a mean of 4.5 years. Combination ART was defined as regimens containing a nonnucleoside reverse transcriptase inhibitor (NNRTI) and/or a protease inhibitor (PI), plus nucleoside analogues (NRTIs). At baseline, 18% of patients had not received ART, 82% had received NRTIs, 35% had received NNRTIs, and 69% had received PIs. Subjects had a mean CD4 count of 418 cells/µL; 26% had AIDS.

Results: Of 52 enrolled subjects, 92% were male and 33% were African American. The median baseline HBV DNA levels in the tenofovir and adefovir groups were 9.5 and 8.71 log₁₀ copies/mL, respectively, with 92% and 82% of subjects in the 2 groups, respectively, positive for HBeAg. A planned interim review, at a median follow-up of 75 weeks, showed that the change in HBV DNA from baseline to week 48 was -4.93 log₁₀ copies/mL in the tenofovir group and -3.12 log₁₀ copies/mL in the adefovir group (intent-to-treat analysis, p = .017). At this analysis, the noninferiority criterion was met, and the study was closed early. The incidence of adverse events, including flares in alanine aminotransferase levels, was similar in the 2 treatment groups; 1 death and 4 withdrawals occurred in each group.

Comment: Tenofovir appears to be safe and effective in the treatment of HBV in HIV/HBV coinfected patients. The study demonstrated that tenofovir is "not inferior" to adefovir in HBV DNA reduction, by protocol definition, and, in fact, suggests that tenofovir may offer superior HBV viral load reduction. For HIV/HBV coinfected patients in whom treatment for both infections is indicated, tenofovir may be a useful component of antiretroviral therapy.