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AbbVie 3D and 2D hepatitis C combos work well for people with HIV and HCV co-infection
Liz Highleyman, 2016-08-05 07:10:00
AbbVie's paritaprevir-based 3D regimen for hepatitis C virus (HCV)
genotype 1 and 2D regimen for genotype 4 were shown to be highly effective and
well tolerated for HIV-positive people with HCV co-infection in the TURQUOISE-I
trial, according to a report at the 21st
International AIDS Conference (AIDS 2016) last month in Durban, South Africa.
New direct-acting antivirals (DAAs) have
brought about a revolution in hepatitis C treatment, offering oral regimens
that are simpler, better tolerated and much more effective than the old
interferon-based therapy. Unlike interferon, the DAAs work as well for
HIV-positive as for HIV-negative people, although HIV/HCV co-infected patients
need to exercise caution about potential drug-drug interactions with
Jürgen Rockstroh of the University of Bonn in Germany reported findings
from the TURQUOISE-I trial part 2, a phase 3 study that assessed the safety and
efficacy of AbbVie's triple and dual DAA regimens -- commonly referred to as '3D'
and '2D' -- taken with or without ribavirin for 12 or 24 weeks for HIV/HCV co-infected
patients with HCV genotype 1 or 4.
The regimen dubbed '3D' during its development
consists of the HCV NS3/4A protease inhibitor paritaprevir, a ritonavir booster
and the NS5A inhibitor ombitasvir in a once-daily coformulation, taken with the
twice-daily HCV NS5B polymerase inhibitor dasabuvir. Dasabuvir is not effective
against genotype 4, so for this indication the
paritaprevir/ritonavir/ombitasvir coformulation is used alone, known as the '2D'
In Europe the three-drug coformulation is sold as Viekirax and the dasabuvir component as Exviera. In the US the combination is
packaged together and sold as Viekira Pak
and paritaprevir/ritonavir/ombitasvir alone as Technivie; the US Food and Drug Administration last week also
approved these components in a once-daily
coformulation called Viekira XR.
The analysis presented at AIDS 2016 included 46 chronic hepatitis C
patients with HCV subtype 1b, 154 participants with harder-to-treat subtype 1a
and 28 with genotype 4. Most (78% of the genotype 1 group and 93% of the genotype
4 group) were men, nearly 90% were white, about 10% were black and the median
age was approximately 50 years. About a third had prior experience with
interferon-based therapy but not other DAAs. The genotype 1 group included 12%
with liver cirrhosis, but the genotype 4 group excluded cirrhotic patients.
HIV status, all were on antiretroviral therapy (ART) and almost all had
undetectable HIV RNA (<40 copies/ml). Median CD4 counts were 614 and 731
cells/mm3, respectively, in the genotype 1 and 4 groups. They were
taking ART regimens that included raltegravir (Isentress), dolutegravir (Tivicay),
ritonavir-boosted darunavir (Prezista)
or boosted atazanavir (Reyataz).
Those using a boosted HIV drug stopped the ritonavir component of their ART
regimen since the paritaprevir coformulation already contains a boosting dose
with HCV genotype 1 were randomly assigned to receive the 3D regimen with or
without ribavirin for either 12 or 24 weeks. All genotype 4 patients were
treated with the 2D combination (no dasabuvir) plus ribavirin for 12 weeks. For
this report patients were pooled into two groups based on genotype, regardless
of cirrhosis status, ribavirin use or treatment duration.
weeks after the end of treatment 97% of people with genotype 1 and 96% with
genotype 4 achieved sustained virological response (SVR12), or continued
undetectable HCV viral load, in an intent-to-treat analysis. In a modified
analysis that omitted participants who were missing data or stopped treatment
for reasons other than virological failure, the corresponding cure rates were
98% and 100%.
prior null responder with genotype 1b experience HCV rebound while on therapy
despite good adherence; this person was found to have several drug
resistance-associated substitutions at the time of failure. Two non-cirrhotic,
treatment-naive genotype 1a patients relapsed after stopping treatment, neither
of whom had resistance-associated substitutions; phylogenetic analysis
indicated that one of these was likely a case of re-infection.
with the 3D and 2D regimens was generally safe and well tolerated. There were
10 serious adverse events, but no cases of liver decompensation or
discontinuations due to adverse events; a serious case of anxiety and
depression syndrome was deemed possibly related to the study drugs. Laboratory
abnormalities included a severe ALT elevation and 28 cases of elevated
bilirubin, almost all of whom were taking atazanavir.
common adverse events were fatigue, nausea, diarrhoea, headache, insomnia and
and pruritus (itching). There were 15 cases of moderate -- but no severe -- anaemia,
all but one in people taking ribavirin; about 10% of ribavirin recipients
modified their dose do to falling haemoglobin levels.
patients (4%) experienced HIV rebound during hepatitis C treatment, but in all
cases this was intermittent and below 200 copies/ml.
results suggest that HIV-1 co-infected patients on certain stable ART regimens
can be treated safely with [ombitasvir/paritaprevir/ritonavir +/- dasabuvir +/-
ribavirin], and there were no HIV-1 virological failures," the
Prof. Rockstroh noted that it was
always a struggle in clinical trials like this to determine if a rise in HCV
viral load after completing treatment is due to late relapse or re-infection.
This is often evident if the renewed infection has a different genotype, but it
would be difficult to distinguish if someone is re-infected with the same