People with HIV and hepatitis B virus (HBV)
co-infection, who substituted tenofovir (Viread) for zidovudine (Retrovir)
or abacavir (Ziagen) in their
antiretroviral regimen, saw a reduction in hepatitis B viral load despite HBV being
resistant to lamivudine (Epivir),
according to a poster presented at the 52nd Interscience Conference on
Antimicrobial Agents and Chemotherapy (ICAAC) last week in San Francisco.
Some antiretroviral drugs, including tenofovir
and lamivudine, are also active against hepatitis B virus. European and US treatment
guidelines recommend that people with HIV/HBV co-infection should include at least one of these drugs in their antiretroviral regimen. Hepatitis B virus rapidly develops resistance
to lamivudine, however, which may compromise its effectiveness.
Kuan-Yeh Lee and colleagues from National Taiwan
University Hospital prospectively evaluated clinical and virological response
to combination antiretroviral therapy when people with HIV/HBV co-infection
switched from zidovudine or abacavir – neither of
which have anti-HBV activity – to tenofovir.
Between November 2010 and August 2012, researchers enrolled 30 people with co-infections who had lamivudine-resistant HBV. At study entry, all had been
taking antiretroviral regimens containing lamivudine as the only drug with
anti-HBV activity. The average duration of lamivudine use was about six years
and the average period of resistance was about two years.
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 count of 481 cells/mm3,
and the median HIV viral load was below 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 log10 copies/ml; one person was triply infected with hepatitis
C.
The researchers measured HBV DNA viral load and hepatitis B surface
antigen (HBsAg) levels at baseline and at regular intervals after
switching drugs. They also periodically assessed HBV drug-resistance mutations,
liver enzyme levels and serum creatinine (a potential marker of kidney
toxicity).
Over an average follow-up period of 44 weeks, median HBV viral load decreases
were larger with longer time on treatment: -2.210 log copies/ml
at week 4, -3.010 at week 8, -2.910 at week 12, -3.810
at week 24, -4.410 at week 36 and -48 log10 copies/ml at
week 48.
The proportion of participants who achieved undetectable HBV DNA (below 128
copies/ml) at these timepoints were 16.7%, 30.0%, 36.7%, 43.3%, 53.6% and
87.0%, respectively.
However, only one of eleven tested participants (9%) experienced HBeAg
seroconversion, and changes in HBsAg levels were described as "negligible"
over time.
The switch to tenofovir was generally safe and well-tolerated. One
person experienced acute hepatitis due to new hepatitis C virus infection. No
other study participants, however, experienced liver enzyme 'flares' or sudden
large increases after changing therapy.
After 48 weeks of follow-up, switching to tenofovir/lamivudine in
HIV/HBV co-infected patients with HBV resistance to lamivudine "was highly
effective in achieving suppression of HBV replication", the researchers
concluded.