A dual combination of Merck's
grazoprevir and elbasvir taken for 12 or 16 weeks cured most HIV-positive
people with genotype 1, 4 or 6 hepatitis C virus (HCV) co-infection and was
generally safe and well-tolerated, according to an integrated analysis of three
trials presented at the recent IDWeek 2015 conference in San Diego, USA.
Grazoprevir (an HCV NS3/4 protease
inhibitor) and elbasvir (a NS5A inhibitor) are being studied as a once-daily
single-tablet regimen for chronic hepatitis C. Both drugs have demonstrated
activity against multiple HCV genotypes. The combination is currently under review by
the US Food and Drug Administration (FDA).
Studies presented at this year's EASL
International Liver Congress showed cure rates of 90% or higher for previously
untreated people (C-EDGE Treatment-naive), prior non-responders to interferon-based
therapy (C-EDGE Treatment-experienced), those unsuccessfully treated with a
first-generation HCV protease inhibitor (C-SALVAGE), people with HIV and HCV co-infection (C-EDGE Co-infected) and people with advanced liver disease (C-SALT) or chronic kidney disease (C-SURFER).
At IDWeek,
Mark Nelson of Chelsea and Westminster
Hospital in London presented findings from an integrated analysis of
all people with HIV and HCV co-infection enrolled in phase 2 and 3 trials of
grazoprevir/elbasvir. Phase 2 studies tested grazoprevir and elbasvir as
separate drugs, while phase 3 trials evaluated the co-formulation.
A total of 298 people with HIV and HCV genotypes 1, 4
or 6 comprised 19% of the phase 2/3 study population (31% of treatment-naive participants
and 3% of those previously treated with pegylated interferon and ribavirin):
About 85% of participants with co-infection were men
(compared with about 60% of participants with HCV mono-infection), with a mean
age of approximately 50 years. About 65% had hard-to-treat HCV genotype 1a,
about 22% had 1b, 12% had genotype 4 and one person had genotype 6. More than
90% were previously untreated; 13% of treatment-naive and 24% of
treatment-experienced participants had liver cirrhosis.
Participants could either be on stable, suppressive
antiretroviral therapy (ART) using tenofovir/emtricitabine (Truvada) or abacavir/lamivudine (Kivexa or Epzicom) plus raltegravir (Isentress),
dolutegravir (Tivicay) or rilpivirine
(Edurant); or else had a CD4 cell
count above 500 cells/mm3 and had not yet started ART.
All 277 treatment-naive participants with HIV and HCV co-infection
were treated with grazoprevir/elbasvir (100mg/50mg)
for 12 weeks; 29 also took ribavirin while 248 did not. The 21 treatment-experienced
participants with co-infection received grazoprevir/elbasvir for 12 or 16 weeks
(about half each); nine people added ribavirin while 12 did not.
Within the treatment-naive group, overall efficacy was
comparable between people with HIV and HCV co-infection and people with HCV
mono-infection, with 94% achieving sustained virological response, or continued
undetectable HCV RNA 12 weeks after completing treatment (SVR12). Treatment-naïve
participants with co-infection had similar response rates using ribavirin-free
and ribavirin-containing regimens (94% vs 97%, respectively).
Within the treatment-experienced group, SVR12 rates
were 100% for people with co-infection receiving grazoprevir/elbasvir with
or without ribavirin for 12 weeks, 83% for those treated without ribavirin for
16 weeks, and 100% for those treated with ribavirin for 16 weeks (numbers in
each study arm were small).
Efficacy was similar regardless of cirrhosis status in
both the treatment-naive and treatment-experienced groups.
Ten treatment-naive and one treatment-experienced participant
with co-infection experienced virological failure, primarily relapse, while six people had treatment failure for
other reasons.
Grazoprevir/elbasvir was generally safe and
well-tolerated for people with co-infection, with no drug-related serious
adverse events or discontinuations due to adverse events. The frequency and
duration of side-effects were comparable between participants with HIV and HCV
co-infection and those with HCV mono-infection. No participants with co-infection
required a change in ART regimen during treatment with grazoprevir/elbasvir.
"High rates of SVR were achieved in patients with
HIV/HCV co-infection," the researchers concluded. "With low rates of
adverse events, once-daily administration, and suitability for use in patients
also receiving antiretroviral therapy, grazoprevir/elbasvir represents a highly
effective treatment option for patients with [HIV/HCV] co-infection."