David Wyles from the University of
California at San Diego presented results from an analysis of response
predictors for people with HIV and HCV co-infection treated with AbbVie's 3D regimen
in the phase 2/3 TURQUOISE-I trial. The main study results were previously reported at the
2014 AASLD (American Association for the Study of Liver Diseases) Liver Meeting.
The regimen consists of the HCV
NS3/4 protease inhibitor paritaprevir, a ritonavir booster and the NS5A
inhibitor ombitasvir in a once-daily fixed-dose coformulation (Viekirax), taken with the twice-daily
non-nucleoside NS5B polymerase inhibitor dasabuvir (Exviera); in the US the complete regimen is sold together as Viekira Pak.
TURQUOISE-I enrolled 63 people with genotype 1 chronic
hepatitis, living in the US. More than 90% were men, three-quarters were white,
about 25% were black and the mean age was approximately 50 years. About 90% had
harder-to-treat HCV subtype 1a and the mean baseline
HCV viral load was approximately 6.0 log10. Two-thirds had not previously taken treatment while a
third had previously tried interferon-based therapy (a mix of relapsers,
partial responders and null responders). About 80% had unfavourable IL28B gene
variants and 19% had cirrhosis.
The median CD4 count was approximately 630 cells/mm3
and they were on suppressive antiretroviral therapy (ART) containing atazanavir
(Reyataz) or raltegravir (Isentress) plus Truvada – drugs found to have no clinically relevant interactions
with the HCV regimen.
Participants in this open-label
study were randomly assigned to receive the 3D regimen plus weight-based ribavirin
for either 12 or 24 weeks.
Overall, 94% of participants in the
12-week arm and 91% in the 24-week arm achieved SVR12. Two people experienced
virological failure: one post-treatment relapse in the 12-week group and one
on-treatment viral breakthrough in the 24-week group. Again, treatment was
generally safe and well-tolerated.
The current analysis looked at
response rates across a variety of demographic and disease characteristics.
However, given that there were just 63 participants in the trial, breaking them
down into subgroups often yielded very small numbers.
There were no notable differences in
the likelihood of response – with SVR12 rates exceeding 90% – based on sex,
race/ethnicity, HCV subtype 1a or 1b, baseline HCV viral load, body mass index,
diabetes status, history of injecting drugs, depression or bipolar disorder,
baseline CD4 cell count or use of atazanavir vs raltegravir.
People over age 55 had a slightly
lower response rate than younger people using the 12-week regimen (88% vs 100%),
but this evened out when treatment was extended to 24 weeks.
The only groups with poorer response
regardless of treatment duration were people with the least favourable 'TT' IL28B
gene variant (89% in the 12-week arm and 80% in the 24-week arm), prior null
responders (80% with either duration) and people with cirrhosis (83% with
either duration). In fact, both participants with virological failure were people
with cirrhosis, categorised as previous null responders with HCV subtype 1a and
IL28B 'TT'.
In people with HIV and HCV genotype 1 co-infection,
the 3D regimen plus ribavirin "achieved high rates of SVR12 regardless of
baseline host, viral and disease characteristics whether treated with 12 or 24
weeks of therapy," the investigators concluded.