Tenofovir at least equivalent to adefovir for treatment of hepatitis B in HIV-infected patients

Tenofovir proved at least as potent as adefovir in controlling hepatitis B virus (HBV) in a study of patients also infected with HIV. Although the results suggested tenofovir may outperform adefovir, Marion Peters, PhD, from the University of California, San Francisco, backed away from that conclusion on statistical grounds.

Adefovir and tenofovir— related nucleotide reverse transcriptase inhibitors—both show activity against HBV, including lamivudine-resistant virus. However, so far only adefovir has been approved to treat HBV infection. Dr. Peters and AIDS Clinical Trials Group (ACTG) colleagues devised a double-blinded, placebo-controlled comparison of the drugs to determine if tenofovir is “noninferior” to adefovir, and presented their findings at the 12^th Conference on Retroviruses and Opportunistic Infections held in Boston, Massachusetts.

The ACTG team evenly randomised coinfected individuals to take 300mg tenofovir once daily or 10mg adefovir once daily. The median CD4+ cell count stood above 400 cells/mm³ in both groups, while three quarters had an HIV-1 RNA load below 400 copies/ml. HBV DNA levels averaged about 9 log₁₀ copies/mL. Three quarters of enrollees had lamivudine experience, and all had been treated with a stable antiretroviral regimen.

An independent review panel recommended closing enrollment after 52 patients had received treatment for a median of 75 weeks. At that point a modified intent-to-treat analysis that included patients with two or more HBV DNA measurements after study entry found a 4.46 log₁₀ copies/ml time-weighted average drop in the tenofovir group vs 3.35 log₁₀ copies/ml with adefovir. An on-treatment analysis found a 4.76 log₁₀ copies/ml fall with tenofovir and a 3.48 log₁₀ copies/ml decrease with adefovir.

Do those differences mean tenofovir is the better drug? Statistically speaking, no. Dr. Peters explained that the early trial termination meant the P value for response difference would have to fall below 0.001 to prove superiority, and the difference was not that great.

A statistical shadow also obscured other evidence suggesting tenofovir’s greater strength. Although the average HBV load fell rapidly and equivalently with both drugs, HBV DNA continued to dwindle with tenofovir after 16 weeks, while the drop leveled out with adefovir. But overlapping confidence intervals around those averages denied tenofovir a “superior” rating.

Side effects and lab abnormalities generally proved equivalent in the 2 treatment arms. Eight individuals taking tenofovir had abnormal amylase or lipase levels, compared with 4 taking adefovir.

Responses in people with lamivudine-resistant virus have yet to be analysed separately.

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