More than 90%
of HIV-positive people treated with direct-acting antivirals for hepatitis C –
including many with liver cirrhosis – achieved sustained virological response
and few discontinued treatment due to side-effects, showing that real-world
clinical practice can produce results as good as those seen in formal clinical
trials, according to results from a Spanish study presented at the 2016 AASLD Liver
Meeting this month in Boston.
HIV-positive people with
hepatitis C virus (HCV) co-infection experience more rapid liver disease progression, on
average, and did not respond as well as HIV-negative people to interferon-based
hepatitis C treatment.
New direct-acting antivirals (DAAs)
used in interferon-free regimens have made treatment simpler, better tolerated
and much more effective. Clinical trials showed that DAAs work as well for
HIV-positive as for HIV-negative people with hepatitis C – so well that
people with co-infection are no longer considered a 'special population' – although they need to
be aware of potential drug-drug interactions with antiretrovirals. But outcomes
in real-life clinical practice sometimes do not match those of formal drug
trials in which participants are carefully selected and may receive more
intensive monitoring and support.
- compensated cirrhosis
The earlier stage of
cirrhosis, during which the liver is damaged but still able to perform most of
its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.
- 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’.
Juan Gonzalez-García of Hospital La Paz and colleagues
evaluated treatment outcomes in the Madrid Coinfection Registry (Madrid-CoRe),
a prospective registry of all individuals with HIV/HCV co-infection receiving
DAA-based hepatitis C treatment at hospitals of the Madrid Regional Health
Service, which are required to register their co-infected patients.
The analysis included 2030 adults with co-infection who
started treatment between November 2014 and May 2016 and who completed therapy
and had long enough follow-up to determine sustained virological response, or
continued undetectable HCV viral load at 12 weeks post-treatment (SVR12).
Relapse was defined as a rebound of HCV RNA levels after the end of treatment.
Nearly 80% of patients in the registry were men and
the mean age was 50 years. Most (95%) were on combination antiretroviral
therapy and the median CD4 count was high at 570 cells/mm3. The most
common HCV genotype was 1a (40%), followed by genotype 4 (22%), genotype 1b
(16%) and genotype 3 (15%).
More than half (55%) did not have cirrhosis, but 37% had
compensated cirrhosis and 7% had decompensated liver disease; 7% had
experienced severe extra-hepatic manifestations of HCV infection. In addition,
15 people had a history of hepatocellular carcinoma, 17 had undergone liver
transplantation and seven were on a transplant waiting list.
Over 60% were being treated for hepatitis C for the
first time. Nearly a third included ribavirin in their regimen. The most common
DAA regimen was sofosbuvir/ledipasvir (Harvoni),
used by 63%, followed by sofosbuvir (Sovaldi)
plus daclatasvir (Daklinza) and the
paritaprevir-based '3D' regimen (Viekirax
+ Exviera), both at 15%. Smaller
numbers used the paritaprevir '2D' regimen (Viekirax
alone), sofosbuvir plus simeprevir (Olysio)
or sofosbuvir plus ribavirin.
The overall SVR12 rate in an intention-to-treat
analysis was 92.0%. Cure rates were similar across HCV genotypes: 92.2% for
genotype 1a, 93.5% for 1b, 91.9% for genotype 3 and 90.4% for genotype 4.
SVR12 rates were 93.7% for people without cirrhosis and 91.5%
for those with compensated cirrhosis, but declined to 80.8% for those with
decompensated liver disease. Cure rates were good for people without cirrhosis
regardless of genotype, but dropped for people with compensated cirrhosis and
especially for those with decompensated cirrhosis. People with cirrhosis with
genotype 1a (77.5%) or 3 (77.3%) had the lowest sustained response rates.
Five people (0.2%) experienced HCV viral breakthrough
while on treatment and 89 (4.4%) experienced post-treatment viral rebound. In
response to a question, Dr Gonzalez-García said the researchers did not have
genotypic data from people with virological failure to determine whether they
experienced relapse or HCV reinfection.
Treatment was generally well tolerated and most people
completed therapy. Fourteen people (0.7%) discontinued treatment due to
adverse events and 36 (1.8%) did so for other reasons. Nineteen people (0.9%)
died during treatment or follow-up, 17 of whom had cirrhosis.
In a multivariate analysis the only significant
predictors of treatment failure were having decompensated cirrhosis – but not
compensated cirrhosis – and use of certain DAA regimens (sofosbuvir plus
simeprevir, sofosbuvir plus ribavirin or simeprevir plus daclatasvir).
"In this large prospective cohort of HIV/HCV co-infected
persons, 45% of whom had liver cirrhosis, the SVR12 [rate] of DAA-based therapy
for HCV infection was >90%," the researchers concluded, and < 1%
discontinued therapy due to adverse events.
These results confirm that treatment outcomes are
similar for people with HIV/HCV co-infection and people with HCV alone, Dr Gonzalez-García
said, adding that the lower response rate for people with decompensated liver
disease is a reason to start treatment earlier.