Tenofovir at least equivalent to adefovir for treatment of hepatitis B in
HIV-infected patients
By Mark Mascolini
February 25, 2005 - 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 12th Conference on Retroviruses and Opportunistic Infections
held in Boston, Massachusetts.
The ACTG team evenly randomized coinfected individuals to take 300 mg
tenofovir once daily or 10 mg 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 2 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 analyzed
separately.
Reference
Peters M, Anderson J, Lynch P, et al. Tenofovir disoproxil fumarate is not
inferior to adefovir dipivoxil for the treatment of hepatitis B virus in
subjects who are coinfected with HIV: results of ACTG A5127. Program and
abstracts of the 12th Conference on Retroviruses and Opportunistic
Infections; February 22-25, 2005; Boston, Massachusetts. Abstract 124. |