The sofosbuvir/ledipasvir (Harvoni) co-formulation used in real-world clinical practice
produced good sustained virological response rates similar to those seen in
clinical trials for HIV-positive people with hepatitis C co-infection, according
to a pooled analysis presented at the 2016 AASLD Liver Meeting this month in
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. Clinical trials have shown that the new direct-acting
antiviral agents used in interferon-free regimens work as well for HIV-positive
as for HIV-negative people with hepatitis C – so much so that people with co-infection are no longer considered a 'special population'. But outcomes in
real-life clinical practice do not always match those of formal treatment
trials in which participants are carefully selected and may receive more
intensive monitoring and support.
Susanna Naggie of Duke University and colleagues
compared the efficacy of the sofosbuvir/ledipasvir single tablet regimen for
people with HIV/HCV co-infection with HCV genotype 1 in clinical trials against its
effectiveness in real-world cohorts.
This analysis looked at results data from three
clinical trials of sofosbuvir/ledipasvir for people with co-infection:
Sciences' ION-4 trial (n = 327)
- The National
Institute of Health ERADICATE trial (n = 50)
- The French ANRS
HC31 SOFTRIH trial (n = 68)
The comparison also included data from four real-world
cohorts with at least 50 participants with co-infection:
- The TRIO cohort
(n = 150)
- The Institute
of Human Virology's ASCEND cohort (n = 142)
- A cohort from
Portugal (n = 166)
- A US Veterans
Affairs (VA) cohort (n = 270)
The cohorts represented diverse patient populations in
the US and Europe treated at academic medical centres, urban primary care
clinics and US Veterans Health Administration facilities.
Across all trials and cohorts the majority of patients
(69-97%) were men, most (60-100%) did not have cirrhosis and the mean ages
were 46 to 60 years. The proportion of treatment-experienced people varied,
but was similar for the trials as a whole and the cohorts as a whole.
Participants had well-controlled HIV with a median CD4 cell count above 600
Clinical trial participants were treated with
sofosbuvir/ledipasvir with or without ribavirin for 12 weeks, while real-world
cohort participants received treatment for 8, 12, or 24 weeks.
In the clinical trials the rates of sustained
virological response at 12 weeks post-treatment (SVR12) for people with genotype 1 who had co-infection were 96% in ION-4, 98% in ASCEND and 100% in ANRS SOFTRIH. SVR12 rates
in the real-world cohorts were 98% in TRIO, 91% in ASCEND, 98% in the Portugal
cohort and 91% in the VA cohort.
In a pooled analysis, the overall SVR12 rates were 97%
for participants in the clinical trials and 94% for patients in
the real-world cohorts. Cure rates were 93% and 92%, respectively, for black
people, 98% and 97% for treatment-experienced people, and 96% and 94% for
people with cirrhosis.
These findings show that people with HIV/HCV co-infection
with HCV genotype 1 can do as well in real-world clinical practice as they did
in clinical trials.
"SVR rates were high across all populations
including populations with traditional negative predictors such as black race,
cirrhosis, and treatment-experienced patients," the researchers concluded.
"This descriptive analysis demonstrated that SVR rates from real-world
cohorts are generalizable from clinical trials."
The results support the latest EASL guidelines and AASLD/IDSA guidelines, which recommend sofosbuvir/ledipasvir for people with
HIV/HCV co-infection, they added.