Hepatitis C virus (HCV) treatment using direct-acting antivirals
(DAAs) is highly effective and safe in harder-to-treat people with HIV
co-infection, Spanish researchers report in AIDS. A sustained
virological response (SVR), or cure, was observed in 93% of people and
only 0.4% stopped treatment because of adverse events. The large
proportion of people had advanced fibrosis or had taken a previous
course of HCV therapy. Liver cirrhosis/liver stiffness were the only
factors associated with treatment failure and use of ribavirin increased
the risk of side-effects.
Nevertheless, 87.5% of people with
cirrhosis achieved an SVR and no one with cirrhosis who completed a
24-week course of treatment and underwent follow-up testing failed to be
cured of hepatitis C. The study findings are highly encouraging for
people with co-infection with advanced liver disease – in the past
considered harder to treat – the study investigators conclude.
“The present work considered a heterogeneous, unselected cohort of
coinfected patients who were treated for their HCV infection under
normal clinical practice conditions, and contrasts well with
highly-selective randomized clinical trials which do not always equate
well to real-life settings,” write the investigators.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
A non-invasive test, used instead of a biopsy, to measure the stiffness
or elasticity of the liver using an ultrasound probe.
type of tumour affecting the lymph nodes.
“The real-life results of studies performed in developed countries
implementing all-oral DAA based regimens in cohorts principally
including difficult-to-treat patients (HIV coinfected, cirrhotic, and/or
with previous therapy failures), confirm these results.”
Approximately a third of HIV-positive people in Spain have
co-infection with HCV. Liver disease caused by HCV is a leading cause of
serious illness and death in people with co-infection. In recent years,
HCV therapy using all-oral DAA regimens has been developed. In clinical
trials, these combinations have achieved SVR rates in excess of 90%.
However, there is relatively little data about the efficacy and safety
of DAA combinations in people with HIV/HCV co-infection with
characteristics usually associated with poorer treatment outcomes,
especially more advanced liver disease or therapeutic failure using
Investigators in eastern Spain therefore analysed outcomes in 515
people with co-infection who started an all-oral DAA regimen in 2015.
Retrospective data were obtained on the proportion of people attaining
an SVR 12 weeks after completing a 12 or 24-week course of therapy, and
also the proportion of people experiencing adverse events. The
investigators also conducted a series of analyses to see if specific
patient or treatment factors were associated with the success of therapy
or a greater risk of side-effects.
A total of 13 treatment centres in the region close to Valencia
participated in the study. The participants had a median age of 50 years
and 78% were male. Most (84%) had injecting drug use as their most
likely mode of HCV infection. The most common HCV genotype was 1a (47%),
with 20% carrying genotype 4 and 14% genotype 1b and 13% genotype 3.
Just over half (54%) had cirrhosis, which was diagnosed using
elastography (FibroScan, an assessment of liver stiffness) in 95%
of people. Just under half (46%) had taken a previous unsuccessful
course of HCV therapy based on pegylated interferon or first-generation
As regards HIV infection, 95% of individuals were taking
antiretroviral therapy (ART) and 90% had a viral load below 50
copies/ml. Median CD4 cell count was 585 cells/mm3. To avoid
potential drug interactions, a third of participants modified their ART
before staring DAA therapy. The new combinations were mostly based on an
The most widely used DAA regimen was ledipasvir/sofosbuvir (57%).
Just over a third of people (37%) were treated with a
ribavirin-containing regimen and 7% took a 24-week course of therapy.
Overall, 93% of people had an SVR 12 weeks after the completion of
therapy. There was little evidence that outcomes were influenced by
baseline characteristics such as age and sex, HCV viral load or previous
use of HCV therapy.
The only factors associated with reduced chances of attaining SVR
were cirrhosis (p = 0.001) and liver stiffness above 21kPa (p = 0.001).
Only two people (0.4%) stopped treatment because of adverse events,
one because of decompensated cirrhosis, the other due to newly diagnosed
high-grade lymphoma. Overall, 37% of people reported any adverse
events. These were mild in the majority of cases. Adverse events were
reported by 54% of the ribavirin-treated patients, with 27% requiring
The investigators’ analyses failed to identify any significant
association between specific DAA regimens and the risk of adverse
events. However, ribavirin was associated with a nearly three-fold
increased risk of side-effects.
“In real-life conditions, difficult-to-treated HIV/HCV-coinfected
patients treated with all-oral DAA combinations reach high rates of SVR12, similar to those achieved by monoinfected patients in such conditions,” conclude the authors.
“Future drugs should be focused on reducing the risk of drug-drug
interactions, along with an improvement in efficacy in patients with
increased liver stiffness.”