Tenofovir, which has potent activity against both
HIV and hepatitis B virus (HBV), is the most effective hepatitis B treatment
for people with HIV and HBV co-infection, according to a 23-study meta-analysis described
in the July 10, 2013 issue of the open-access journal PLoS One. Combining tenofovir with FTC did not improve
hepatitis B response.
to overlapping transmission routes, many people are co-infected with both HIV
and HBV. A few antiretroviral drugs approved for HIV are also active against
HBV, including 3TC (lamivudine, Epivir),
FTC (emtricitabine, Emtriva), and tenofovir (Viread). 3TC and FTC have similar structure
and antiviral activity, though the former appears more prone to resistance;
virus that develops resistance to one of these drugs will typically be
cross-resistant to the other.
Huw Price from University College London and colleagues
performed a systematic review and meta-analysis looking at outcomes among
people with HIV and HBV co-infection treated with tenofovir, stratified by prior or
concurrent use of 3TC and FTC.
Tenofovir has been shown to be highly
effective against hepatitis B and has a low
barrier to resistance. However, several questions remain unanswered about
tenofovir for people with HIV and HBV co-infection, the study authors noted as
background, including the proportion who achieve HBV viral load suppression and
how long it takes, whether suppression is durable and whether prior treatment
with other HBV-active drugs compromises tenofovir effectiveness due to viral
The researchers analysed data from 23 mostly
observational studies that included a total of 550 people with HBV and HIV co-infection who had taken tenofovir. Duration of follow-up lasted up to seven years, but the
main analysis was limited to three years in order maintain a large enough
number for sufficient statistical power.
Overall, the proportion of study participants achieving full
suppression of HBV replication after one year of treatment was 57%. Viral
suppression rates increased to 79% at two years and 86% at three years. Among
participants followed for longer periods, the proportion with undetectable HBV
increased to 100%, though patient numbers were small. Virological rebound
during tenofovir treatment was rare (2.4%).
Adding 3TC or FTC to tenofovir was not
associated with significant improvement in treatment response. Use of 3TC or FTC in the past did not significantly impair current
response to tenofovir.
suppresses HBV to undetectable levels in the majority of HBV/HIV co-infected
patients with the proportion fully suppressed continuing to increase during
continuous treatment", the study authors concluded. "Prior treatment
with [lamivudine or emtricitabine] does not compromise efficacy of [tenofovir]
treatment. The use of combination treatment with [lamivudine or emtricitabine]
offers no significant benefit over [tenofovir] alone."
In their discussion,
they explained that the treatment response rate for people with HIV and HBV co-infection in this analysis was lower than rates seen in studies of HIV-negative
people with HBV alone: around 80 to 90% at one year and 90 to 100% at two years, with
better response among people who were hepatitis B 'e' antigen (HBeAg) negative compared with
people who were HBeAg positive.
Although not apparent in this analysis, some prior
studies have seen higher viral breakthrough rates for people with co-infection than
for those with HBV alone. Among people with co-infection taking 3TC as their
only HBV-active drug, about 90% develop resistance, while HBV resistance to
tenofovir is rare.
a limitation of their analysis, the authors noted that most of the included
studies were observational, and participants who dropped out were not well
characterised. Only two studies compared people randomly assigned to
different treatment arms.
Another limitation is that
the analysis did not include adverse events (side-effects). While tenofovir is generally safe
and well-tolerated, it can cause bone loss and kidney impairment in susceptible
individuals. "Future studies with longer follow-up duration will be
required to determine the risk of treatment-associated adverse effects, such as
renal and bone toxicity, in patients exposed to [tenofovir] for many
decades", they wrote.