Effective interferon-based therapy
that produces sustained virological response led to significant reductions in
liver decompensation, HIV disease progression and both overall and
liver-related mortality among people with HIV and hepatitis C co-infection, according to a
presentation at the 53rd Interscience Conference on Antimicrobial Agents and
Chemotherapy (ICAAC) last week in Denver.
Over years or decades, chronic hepatitis C virus (HCV) infection can lead
to severe liver disease including cirrhosis and hepatocellular carcinoma, a
type of liver cancer. People co-infected with both HIV and HCV tend to
experience more rapid liver disease progression and respond less well to
interferon-based therapy than those with hepatitis C alone. HIV-negative people with hepatitis C are generally not
treated if they have mild to moderate liver disease, but people with co-infection may benefit from earlier therapy due to their risk of more
Juan Berenguer from Hospital Gregorio Marañón and fellow investigators
with the GESIDA 3603 HIV/HCV Cohort Study looked at the effects of successful
interferon-based therapy on liver disease progression and death amongst people with HIV/HCV
co-infection who didn't have advanced liver fibrosis at baseline.
While the clinical benefits
of sustained virological response (SVR), or continued undetectable viral load
12 or 24 weeks after completing treatment have been well characterised for people with co-infection who have advanced liver disease, outcomes for people with co-infection who have milder
liver damage are less well understood, the researchers noted as background.
analysis included 695 participants in the GESIDA 3603
cohort, a group of co-infected patients at 19 clinical centres in Spain who
started treatment with conventional or pegylated interferon plus ribavirin
between January 2000 and January 2008.
About three-quarters of participants
were men, most were white, the median age was 40 years and more than 80% had a
history of injection drug use. The median CD4 T-cell count was high, at 546
cells/mm3, but 20% had a history of AIDS (CDC Category C disease).
Two-thirds of participants had
difficult-to-treat HCV genotypes 1 or 4, the rest genotypes 2 or 3.
Pre-treatment liver biopsies showed that 11% did not have fibrosis (Metavir
stage F0), 42% had mild fibrosis (F1) and 47% had moderate fibrosis (F2).
People with bridging fibrosis (F3) or cirrhosis (F4) were not included in this
The researchers looked at various
liver-related outcomes including liver decompensation (inability to perform
critical functions), hepatocellular carcinoma, liver transplantation,
liver-related death and all-cause mortality. Assessments of liver damage were
made using biopsies and transient elastometry (FibroScan), a non-invasive
method that uses sound waves to measure liver stiffness.
Overall, 35% of study participants
achieved sustained response. Factors significantly associated with greater
likelihood of SVR included HCV genotype 2 or 3 vs 1 or 4 (odds ratio [OR] 4.24),
pre-treatment HCV viral load <500,000 IU/ml (OR 1.88) and no heavy alcohol
use (<50 g/day; OR 4.04). Liver stiffness scores decreased significantly
more following treatment amongst people who achieved SVR.
Over a median follow-up period of 59
months, event rates for people with and without SVR were as follows:
- Liver decompensation: 0.26 vs 0.84 per 100 person-years
carcinoma: 0.13 vs 0 per 100 person-years
mortality: 0 vs 0.09 per 100 person-years
- All-cause mortality:
0.39 vs 0.63 per 100 person-years
- Progression to AIDS: 0.13 vs 0.55 per 100 person-years.
Participants who achieved SVR were
significantly less likely than non-responders to experience liver
decompensation (1.1 vs 6.2%; p =.010) and all liver-related events
(p<0.001). Successfully treated patients were also less likely to experience
HIV disease progression to AIDS (0.7 vs 3.3%; p<0.05).
People with sustained response were
found to have significantly lower liver-related mortality (0.4 vs 2.6%;
p = 0.024) and overall mortality (1.5 vs 5.2%; p = 0.010).
However, when results were broken
down by pre-treatment liver disease stage, differences in outcomes (except for
AIDS) remained significant only for people with moderate fibrosis (F2), not for
those with absent or mild fibrosis (F0-F1).
"Eradication of HCV in HIV/HCV
co-infected patients with non-advanced liver fibrosis (F0 to F2), and, more
specifically, with moderate stages of liver fibrosis (F2), is associated with a
reduction in the risk of mortality and liver-related events," the
"These findings constitute a
strong rationale for considering anti-HCV treatment in this population group,
particularly treatment based on the newer and more effective direct antiviral
agents," they added.
Following the presentation Joseph Eron
noted that numbers of people with specific fibrosis stages were small, so we
cannot assume treatment conferred no benefit for people with less advanced
liver disease. Dr Berenguer agreed, stating, "I think if we follow them
longer, even patients with mild fibrosis would get benefits."
Berenguer and Jose Miro from the
University of Barcelona, who discussed liver transplantation at the same
session, both acknowledged that their presentations were largely history due to
the advent of effective new direct-acting anti-HCV drugs.
Interferon/ribavirin dual therapy
cures only about half of people with HCV genotype 1 – even less among those with HIV –
with a year of difficult-to-tolerate therapy. This is currently being replaced
by triple therapy with add-on HCV protease inhibitors, bringing cure rates up
to around 75% even for people with co-infection. Next-generation antivirals now
under study, which will first be used as interferon add-ons and eventually in
all-oral regimens, promise to bring SVR rates into the 80 to 100% range with
shorter, better-tolerated courses of treatment.
Without the disadvantages of year-long therapy, potentially severe side-effects
and suboptimal response rates, people with HIV/HCV co-infection will have more
incentive to undergo treatment that reduces their long-term risk of liver
failure and death.