Download December 2013 - Project Inform

I n f o r m at i o n , i n s p i r at i o n a n d a d v o c a c y f o r p e o p l e w i t h H I V/A I DS a n d h e pat i t i s C
p2
HCV CARE NEWS
Newly published US Hepatitis C Treatment Cascade,
from the DHHS.
HCV CARE NEWS
p6
p7
Successful inteferon-free
treatment is possible for
liver transplant patients.
HCV CARE NEWS
Interferon-free regimen
may be possible for most
co-infected individuals.
STAFF WRITERS
David Evans, Director of
Research Advocacy
Alan McCord, Director of
Education
Andrew Reynolds, Hepatitis
C Education Manager
P. I . p e r s p e c t i v e | SEPTEM B ER 2 0 1 3 | 2 7 3 Ni n t h S t r e e t , S a n F r a n c i s c o , CA 9 4 1 0 3 | w w w . p r o j e c t i n f o r m . o r g
Reportback from the 2013 AASLD in Washington, DC
In this issue of PI Perspective, Project Inform reports on data that was presented at the
annual meeting of the American Academy for the Study of Liver Disease in Washington, DC from
November 1–5, 2013, with additional coverage from Infectious Disease Week in October and
HEP DART in December.
A long journey ahead of us: Ending the silent epidemic of viral hepatitis
by Andrew Reynolds, Hepatitis C Education Manager
Throughout AASLD 2013, there was significant excitement around the promise that many of the new therapies
hold for curing HCV. While these treatments are certainly
exciting, the United States has a long way to go to uncover
new cases of HCV and link people to medical care.
On the final day of the conference, Ronald Valdiserri,
MD, Deputy Assistant Secretary for Health, Infectious
Diseases and Director, Office of HIV/AIDS and Infectious
Disease Policy, delivered a talk entitled “Ending the Silent
Epidemic of Viral Hepatitis in the US” where he highlighted the problem of increasing cases of HCV infections, and
the challenges of linking to care and successfully treating
people once they are diagnosed with the virus.
The most recent data presented (2011) shows an estimated 16,500 new HCV infections each year — a 45%
increase from 2010. In a sobering comparison, Valdiserri reported the 2010 estimated HCV-related deaths
at 16,627. With deaths out-pacing new infections, one
might get the false impression of decreases in HCV rates
in the United States.
A truer picture of HCV in the United States came
about when he introduced the “U.S. HCV Treatment
Cascade” (figure below). The cascade highlights that only
1.6 million or 50% of the 3.2 million people living with
HCV have been diagnosed, with only 1 to 1.2 million or
32-38% of those with HCV referred to medical care. For
those who are engaged in medical care, only 220,000 to
360,000 (7-11%) of the total population living with HCV
u CONTINUED: page 2
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
|
2
w w w. p r o j ec t i n fo r m .o r g
has received treatment for the disease, and only 170,000
to 200,000 (5-6%) has been successfully treated.
As HCV therapies improve, it is widely accepted that
more patients and medical providers will opt for starting
treatment. But as Dr. Valdiserri’s presentation demonstrates, the U.S. must improve its HCV screening and linkage to care infrastructure in order to ensure that all people
living with HCV have access to these treatments and wipe
out this curable disease.
SOURCE:
Valdiserri, R. Ending the Silent Epidemic of Viral Hepatitis in the US. AASLD 2013, Washington DC, November
1-5, 2013.
U.S. Hepatitis C Treatment Cascade
3.2 MILLION AMERICANS WITH HEPATITIS C
(3.2 million Americans living with chronic hepatitis C)
100%
80%
60%
1.6 M
40%
1.0–1.2 M
20%
220,000–
360,000
0%
Diagnosed
Referred
to care
Treated
170,000–
200,000
Successfully
treated
PEOPLE WHO ARE ENGAGED IN HIV CARE
SOURCE: Holmberg, et al, “Hepatitis C in the US”, N Eng J Med 2013, 1,859–1,861.
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
|
w w w. p r o j ec t i n fo r m .o r g
3
A three-drug regimen cures more than 90%
of HCV genotype 1 without interferon or ribavirin
by Andrew Reynolds, Hepatitis C Education Manager
A Phase 2b study of three oral medications taken twice a
day achieved an SVR12 in over 90% of people with HCV
genotype 1. The regimen includes daclatasvir (DCV), asunaprevir (ASV) and BMS-791325.
This study had 166 people included in it: 80 participants who took DCV 30mg, ASV 200mg and BMS-791325
75mg all twice a day, and 86 participants who took the
same regimen but took a 150mg dose of BMS-791325.
The average age in the study was 54. Men comprised
67% of the participants while 83% were Caucasian and
16% were African American. All of the participants were
treatment naïve and all had genotype 1, with 82% having GT 1a. A relatively large number had advanced liver
disease: 38% had a fibrosis score of F3 or F4, and 9%
had cirrhosis. The IL28B genotype distribution was as
follows: 33% CC, 50% CT and 16% TT. (CT and TT do not
respond as well to treatment as CC.)
The end of treatment response rates for each regimen
was very high: 97.5% for the first group taking the 75mg
regimen and 94.2% for the 150mg regimen. By patient
subgroups, 100% of the cirrhotic patients on the 75mg
regimen achieved SVR12, and 91% achieved SVR12 in the
IL28B non-CC genotypes. Additionally, 91% of GT1a and
100% of GT1b achieved an SVR12 on the 75mg regimen.
Eleven participants experienced virologic failure,
and all had GT 1a. There were 6 virologic failures in the
75mg group, of which 2 were viral breakthroughs. There
were 5 virologic failures in the 150mg group, with 3 viral
breakthroughs. In both groups, the viral relapse occurred
before post-treatment week 4. Drug resistance was noted
in 17 patients, but 13 of them still achieved an SVR12.
Both regimens were well-tolerated: 8 people stopped
treatment, although 6 of them came from the 150mg
regimen. Lack of efficacy, such as viral breakthrough, occurred in 3 of the 6, while no one in the 75mg regimen
experienced a viral breakthrough. The most commonly
reported side effects were headaches (25%), diarrhea
(15%), fatigue (11%) and nausea (10%). Some lab abnormalities were noted, but none appeared related to the
HCV therapy.
This regimen marks another advance in the treatment of hepatitis C. Phase III studies of the 75mg regimen in a full-regimen pill have recently begun, and future results will be presented and discussed in scientific
conferences and journals. If the results from this larger
study prove to be as effective as the one reported here,
there will be another option for people with hepatitis C
to choose from to get cured, particularly for patients with
GT 1a, advanced liver disease, or hard-to-treat IL28B
non-CC genotypes.
SOURCE:
Everson, G., et al. Phase 2b Study of the Interferon-Free
and Ribavirin-Free Combination of Daclatasvir, Asunaprevir, and BMS-791325 for 12 Weeks in TreatmentNaïve Patients with Chronic HCV Genotype 1 Infection.
AASLD 2013, Washington DC, November 1-5, 2013.
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
|
w w w. p r o j ec t i n fo r m .o r g
4
New all-oral drug combination holds great promise of
high cure rate for hepatitis C genotypes 1a and 1b
by Andrew Reynolds, Hepatitis C Education Manager
Dr. Eric Lawitz and colleagues reported on the results
from the C-Worthy study, which looked at the efficacy
and safety of two new Merck drugs with and without
ribavirin in three different all-oral regimens. The drugs
being studied included MK-5172 (NS3/4A protease inhibitor) and MK-8742 (NS5A replication complex inhibitor). Although it was a small study, the results were very
promising with 59 of 60 participants (98%) receiving an
SVR12.
C-Worthy was broken up into 3 arms, each looking
at a specific regimen. Arm 1 had 33 people with genotype
1a or 1b who took 100mg MK-5172 once a day + 20mg
MK8742 once a day + ribavirin. Arm 2 had 27 people
with genotype 1a or 1b who took 100mg MK-5172 once
a day + 50mg MK8742 once a day + ribavirin. Finally,
Arm 3 comprised of 13 people with genotype 1b who took
100mg MK-5172 once a day + 50mg MK8742 once a day.
All participants had no to mild fibrosis, and no one was
co-infected with HIV or HBV.
All participants took 12 weeks of therapy. Everyone
in arms 1 and 3 reached 100% SVR, while those in arm
2 achieved 96% SVR. (One participant had an HCV viral
relapse at week 4 after stopping treatment.)
In all cases, the regimens were very well tolerated,
and no one stopped treatment due to side effects or adverse events. Nine people who took ribavirin developed
anemia, but none so severe as to lead to discontinuation.
The most commonly reported side effects were fatigue
(26%), headaches (22%) and nausea (18%).
For patients with HCV who are seeking a once daily regimen without interferon (and in some cases ribavirin), the results of this study hold great promise. Although further study will be done on these medications
— including looking at its effectiveness in individuals
with more severe liver disease and those with HIV/HCV
co-infection — this regimen may eventually become another effective tool in our fight against HCV.
SOURCE:
Lawitz, E., et al. High Efficacy and Safety of the AllOral Combination Regimen, MK-5172/MK-8742 + RBV
for 12 Weeks in HCV Genotype 1 Infected Patients: The
C-Worthy Study. AASLD 2013, Washington DC, November 1-5, 2013.
Promising once-daily regimen for treatment hepatitis C genotype 1
by Andrew Reynolds, Hepatitis C Education Manager
A new interferon-free regimen of sofosbuvir (SOF) + ledipasvir (LDV) achieved a high cure rate of SVR12 weeks in
both treatment naïve and experienced patients with and
without ribavirin (RBV). This group also included individuals with cirrhosis, who showed similar treatment responses
as those with healthier livers. This marks an exciting point
in the development of HCV therapies for both those with
earlier treatment failures and those with cirrhosis.
The LONESTAR Study included 100 people: Cohort
1 included 60 people who were treatment naïve and did
not have cirrhosis while cohort 2 consisted of 40 people
who had earlier treatment failures and 50% of whom
also had cirrhosis. Within each cohort, patients took ei-
ther SOF + LDV or SOF + LDV + RBV for 8 or 12 weeks.
Treatment effectiveness and safety, potential drug resistance and drug interactions were all monitored.
Study participants were on average 50 years old (21–
73 years) and were 66% male. Most participants were
Caucasian, with Hispanic representation at 40% and
African American at 9%. The vast majority (87%) had
genotype 1a, and 15% had the IL28B CC genotype, who
respond better to treatment.
At the end of 12-weeks of treatment, 97% achieved an
SVR12. All but two in Cohort 1 achieved an SVR12, while
in Cohort 2 all but 1 successfully achieved an SVR12.
u CONTINUED: page 5
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
Of the 3 people who experienced a viral relapse, none
of them took ribavirin. One was also lost to follow-up after week 8. In addition to the 3 treatment failures, drug
resistance was detected in several patients: 9% developed NS5A resistance and 70% in the treatment experienced group developed NS3/4a resistance. Two people
with NS5A resistance did not achieve an SVR, but all of
the others did.
Overall, the treatment of SOF/LDV was extremely
well tolerated, with no one stopping treatment due to
adverse events. Nausea (5%), headaches (5%), and upper respiratory infection (7%) were reported, with no one
becoming anemic. In those who took SOF + LDV + RBV,
19% became anemic, and they all experienced similar
side effects as the other group but at slightly higher rates.
|
w w w. p r o j ec t i n fo r m .o r g
5
People living with hepatitis C would benefit from a
simple, once-daily regimen that is effective and easy to
take with few side effects. Although more research is
needed, these early results are very promising and also
offer hope for people with cirrhosis and those who were
prior treatment failures.
SOURCE:
Lawitz, E., et al. Sofosbuvir and Ledipasvir Fixed-Dose
Combination with and without Ribavirin in TreatmentNaïve and Previously Treated Patients with Genotype
1 Hepatitis C: The LONESTAR Study. AASLD 2013,
Washington DC, November 1-5, 2013.
COSMOS Study supports interferon-free regimens for hepatitis C genotype 1
by Andrew Reynolds, Hepatitis C Education Manager
By the end of 2013 both simeprevir (Olysio, SMV) and
sofosbuvir (Sovaldi, SOF) were approved by the FDA.
This approval will be for the treatment of HCV genotype 1 together with both interferon and ribavirin. (Note:
For treating GT 2 and 3, sofosbuvir was approved with
ribavirin only, eliminating the need for interferon for
people with these two genotypes.) Although neither drug
was submitted to be used together, the COSMOS Study
looked at the effectiveness of this regimen for treating
GT1 without pegylated interferon.
COSMOS is a Phase 2a, randomized, open label study
investigating the efficacy of simeprevir + sofosbuvir, taken with and without ribavirin (RBV). Eighty participants
were assigned to 2 groups. Cohort 1 included individuals who were prior null-responders (tried treatment but
not successful), and Cohort 2 included people who were
either new to treatment or prior null responders. Each
cohort included people with varying degrees of cirrhosis.
Finally, each cohort had different groups of treatment
length of 12 or 24 weeks to determine the most effective
treatment duration.
Cohort 1 was 61.3% male, with an average age of 56.
African Americans made up 29% of participants, and another 25% were Hispanic. This cohort included people
Metavir scores of F0-1 (41%) and F2 (59%). All had either
genotype 1a (78%) or 1b (23%). Additionally, 50% of GT
1a participants had the Q80K genetic mutation (which
can negatively impact the effectiveness of simeprevir).
Finally, 6% had the favorable IL28B CC genotype, 70%
had the CT genotype, and 24% had the TT genotype.
Cohort 2 was 67% male with an average age of 58. African Americans made up 9% of study participants, and an
additional 17% were Hispanic. This cohort had 46% treatment naïve participants and 54% prior null responders.
These participants had more serious liver disease, with
Metavir scores of F3 (53%) and F4 (47%). All had either
genotype 1a (78%) or 1b (22%). Additionally, 40% of GT
1a participants had the Q80K mutation. Finally, 21% had
IL28B CC genotype, 56% had CT and 23% had TT.
Everyone in the 12-week groups completed treatment. At the end of treatment all participants had undetectable HCV RNA with no virologic breakthroughs.
Within Cohort 1, 96.3% of those on the SMV+SOF+RBV
regimen achieved an SVR12, while 92.9% of those on
SMV+SOF achieved an SVR12. In Cohort 2, 100% of the
treatment naïve participants achieved an SVR12 for both
regimens, while 100% of the null responders on SMV
+SOF achieved an SVR12 and 93.3% on SMV+SOF+RBV
achieved an SVR12 . Participants with non-CC genotypes
achieved an SVR12 of 96% on both regimens. Partici-
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
pants with a Metavir score of F4 achieved a 100% SVR12
on SMV+SOF, while 91% did on SMV+SOF+RBV. Prior
null responders in both treatment regimens achieved an
SVR12 of 95%.
Both regimens were very well tolerated. No one
who took 12 weeks of treatment stopped due to adverse
events. The most commonly reported side effects on the
SMV+SOF regimen were fatigue (25%), headaches (21%)
and nausea (21%). No one from this group became anemic.
The results were similar on the SMV+SOF+RBV regimen, with the same side effects reported, though an additional 15% reported a rash and 11% did become anemic.
In closing, the results for this study hold much promise for regimens without interferon or ribavirin, offering
|
w w w. p r o j ec t i n fo r m .o r g
6
hope for those patients who are unable or unwilling to
take these medications. We still need to wait for the final
analysis, but in the meantime — although this combination is not yet FDA approved — there may still be medical
providers willing to prescribe this off-label regimen for
their patients.
SOURC:
Jacobson, I., et al. SVR Results of Once-Daily Regimen
of Simeprevir (SMV, TMC435) plus Sofosbuvir (SOFm
GS-7977) with or without Ribavirin in Cirrhotic and
Non-Cirrhotic HCV Genotype 1 Treatment-Naïve and
Prior Null Responder Patients: The COSMOS Study.
AASLD 2013, Washington DC, November 1-5, 2013.
Successful interferon-free treatment possible for liver transplant patients
by Andrew Reynolds, Hepatitis C Education Manager
The regimen of sofosbuvir + ribavirin showed very promising early results for treating hepatitis C (HCV) in liver
transplant patients. The treatment was well-tolerated,
and no drug interactions were seen between the HCV or
immunosuppression medications. Interferon-free HCV
regimens with few drug interactions are an important
clinical development for liver transplant patients.
HCV reinfection of a transplanted liver in patients
with active disease is a serious health challenge, as the
progression to cirrhosis is often rapid and/or the infection can lead to liver graft failure. The current medications for treating HCV can be very challenging to use with
immunosuppression drugs, resulting in poor efficacy and
significant drug interactions.
This small study included 40 patients. All had received a liver transplant, and both treatment naïve and
experienced individuals were included. Patients with
signs of decompensation or use of corticosteroids (>5mg
of prednisone) were excluded. Participants were mostly
men (78%, n=31), had an average age of 59, and were
mostly Caucasian (85%, n=34). Genotypes 1a, 1b, 3 and
4 were included, and 35 (88%) had been on HCV treatment before. The average time after liver transplant was
4.3 years. Finally, 40% (n=16) had cirrhosis, 35% (n=14)
had portal fibrosis, and 23% (n=9) had bridging fibrosis.
The 24-week treatment consisted of 400mg sofosbu-
vir + 400-1200mg ribavirin (patients started with 400mg
and gradually increased based on lab results). Within the
first 4 weeks, 100% had undetectable HCV viral loads as
did 100% of those who completed (n=39) the treatment
at 24 weeks. At four weeks after then end of treatment,
77% maintained an undetectable viral load.
The regimen was fairly well tolerated, with 2 patients
stopping due to an adverse event. The most common side
effects were fatigue (28%), headache (25%), joint pain
(23%) and diarrhea (23%). Cough, nausea and anemia
were also reported but less often. There were no deaths,
graft losses or episodes of rejection reported.
An SVR4 of 77% is good news, but it is far too early to
determine if these patients are cured. These patients will
continue to be observed, and the results will be reported
at future conferences. That said, this is an important development in our treatment options for post-transplant
patients and offers hope for effective regimens without
interferon for this population.
SOURCE:
Charlton, M., et al. Sofosbuvir and Ribavirin for the
Treatment of Established Recurrent Hepatitis C Infection After Liver Transplantation: Preliminary Results
of a Prospective, Multicenter Study. AASLD 2013,
Washington DC, November 1-5, 2013
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
|
w w w. p r o j ec t i n fo r m .o r g
7
New results show an interferon-free regimen
may be possible for some co-infected with HIV and HCV
by Andrew Reynolds, Hepatitis C Education Manager
The interferon-free regimen
PHOTON-1 RESULTS
of sofosbuvir (Sovaldi) + ribaGenotype #
HCV tx On HIV tx HCV SVR 12 Tx failures Relapses
virin showed high sustained
1a / 1b
114
24 wks
98%
82% / 54%
1
25
virologic response (SVR) rates
for HIV/HCV co-infected in2
26
12 wks
85%
88%
1
0
dividuals in the PHOTON 1
3
42
12 wks
93%
67%
12
12
study. This regimen had no
drug interactions with HIV
and nausea were the most commonly reported side efmedications, and did not negfects, and one person stopped due to adverse events.
atively impact CD4 T-cell percentages. Additionally, the
A total of 42 patients with GT3 enrolled, and 93% of
treatment was very well tolerated, with very few people
them
were taking HIV treatment. Within this group, 81%
stopping due to side effects or adverse events.
of whom were male, 5% were African American and 26%
PHOTON-1 is an open-label study that included 223
Latino/a. This group also took 12 weeks of HCV therapy,
co-infected persons with HCV genotypes 1, 2 and 3. Inbut only 67% (28/42) reached an SVR. HCV virologic
dividuals were given 400mg Sovaldi and a weight-based
failure occurred in 12 people during treatment, and HCV
dose of ribavirin for either 12 or 24 weeks, depending on
viral relapse occurred in another 12 after treatment had
genotype and prior treatment history. Nearly all particistopped. Side effects were also similar to the GT2 group,
pants were on HIV treatment or had CD4 counts above
with 3 people stopping therapy due to adverse events.
500 cells. People with cirrhosis were allowed in this study
For all participants, regardless of genotype, no drug
but very few enrolled.
interactions interfered with either HIV or HCV treatment
Among those with GT1, there were 114 participants,
effectiveness. There was a small drop in the absolute CD4
98% of whom were on HIV treatment. Among them, 82%
count, but this is to be expected with ribavirin. There was
were male, 33% African American, and 22% Latino/a.
no change in CD4 cell percentage. Two individuals deThese participants were given 24 weeks of sofosbuvir +
veloped detectable HIV viral load, but in both cases poor
ribavirin and 76% (87 of 114) achieved an SVR12.
adherence to HIV treatment was the cause.
It is important to further distinguish these results
With all of the advances in HCV therapies, we still need
by sub-type: GT1a had an SVR of 82% while GT1b was
to
find
safe and effective regimens for co-infected persons.
54%. For both GT 1a and 1b, HCV on-treatment failure
With interferon-free regimens on the horizon for HCV mowas limited to 1 person, while 25 people had an HCV vino-infected persons, this study showed comparable results
ral relapse after treatment. Treatment was generally very
for co-infected persons. Side effects were minimal, drug inwell tolerated with fatigue, nausea and headaches most
teractions were not a problem, and CD4 counts were only
commonly reported. Three people had to stop HCV treatmildly affected. This marks an exciting development in the
ment due to adverse events.
treatment of HCV in people living with HIV.
Among those with GT2, 85% of the 26 people were
taking HIV treatment. As for demographics, 81% were
SOURCE:
male, 23% African American and 31% Latino/a. These
Sulkowski, M., et al. All-Oral Therapy with Sofosbuvir
participants took 12 weeks of HCV treatment and 88%
Plus Ribavirin for the Treatment of HCV Genotype
(23/26) reached an SVR12. The on-treatment HCV viro1,2, and 3 Infection in Patients Co-Infected with HIV
logic failure was limited to 1 person, and no one experi(PHOTON-1). AASLD 2013, Washington DC, November
enced an HCV relapse after treatment. Fatigue, insomnia
1-5, 2013.
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
|
w w w. p r o j ec t i n fo r m .o r g
8
Treating hepatitis C in HIV/HCV co-infected people:
A new option on the horizon
by Andrew Reynolds, Hepatitis C Education Manager
A new HCV protease inhibitor faldaprevir, used together with pegylated interferon + ribavirin, showed a high
4-week sustained virologic response (SVR4) of 74% in
HIV/HCV co-infected people. These are early results and
therefore may change as people are again tested at 12
weeks. These results offer hope for a more effective treatment of HCV in co-infected people.
Approximately 300,000 people are co-infected with
HIV and HCV, who are at risk for a more rapid liver
disease progression and end-stage liver disease. (HCVrelated liver disease is the leading cause of non-AIDS
related deaths.) To date, the FDA-approved treatment
options have been limited to using pegylated interferon
(PI) + ribavirin (RBV) or the off-label use of Incivek or
Victrelis + PI + RBV. (Note: at press, Sovaldi has received FDA approval for treatment of HCV in co-infected
individuals.)
Entitled “STARTVerso4”, this is one of a series of
studies looking at the effectiveness of faldaprevir in
various populations and together with other HCV medications. This phase 3 study included 308 co-infected
people; most of whom were men (81%) and Caucasian
(83%). Average age was 47. All participants had either
HCV genotype 1a (79%) or 1b (21%). Most participants
(85%) did not have cirrhosis but in those who did, 29%
had advanced fibrosis (F3/F4). Finally, 78% were treatment naïve for HCV, most were on HIV treatment, and
only 4% had never taken HIV meds.
The overall SVR4 for this study was 74%, and it was
evenly distributed between genotype 1a (74%) and 1b
(77%). For those without cirrhosis 74% achieved an SVR4
while 77% of those with cirrhosis achieved an SVR4. It is
also noteworthy that 87% of individuals who did not respond to earlier treatment achieved an SVR4 (compared
to 71% of those who were treatment naïve). The SVR4
were achieved in a fairly even distribution across various
HIV treatment regimens ranging from 67–80% (including an SVR4 of 73% in those not on HIV meds).
Researchers concluded that the HIV meds used did
not have significant drug interactions. While nearly all
participants (98%) experienced a medication side effect
or adverse event, only 1% of people had to stop faldaprevir while 7% had to stop all medications. The most commonly reported side effects were nausea (37%), fatigue
(34%), diarrhea (27%), headache (25%), loss of strength
(23%) and loss of appetite (21%). Additionally, 44% of
participants were given a grade 3 or higher abnormality
on blood work.
As we fully enter the era of “Directly Acting Antivirals”, we are witnessing significant advances in HCV
therapies, with many more HCV drugs on the horizon for
people living with HIV. That said, most of these drugs
have only been studied in mono-infected persons. With
this and many other studies underway, the hope is that
HIV/HCV co-infected people will be able to reap the same
benefits from HCV treatment as mono-infected persons.
SOURCE:
Rockstroh, JK, et al. STARTVerso4 Phase III Trial of
Faldaprevir plus Pegylated Interferon and Ribavirin in
Patients with HIV and HCV Genotype 1 Co-Infection.
AASLD 2013, Washington DC, November 1-5, 2013.
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
|
w w w. p r o j ec t i n fo r m .o r g
9
Other conference coverage: HEP DART and ID WEEK
by Andrew Reynolds, Hepatitis C Education Manager
Several conferences were held in the last few months of
2013 that were relevant for treating and care of hepatitis C:
Infectious Disease Week (October), AASLD (November),
and hepDART (December). There were a variety of important presentations throughout, and the following offers a review of some of the highlights from these three
conferences.
CONFERENCE: HEP DART 2013
This annual conference has been convening since 1995 and
describes its mission as follows: “The focus of HEP DART
2013 is to assemble clinicians, researchers and basic scientists together to advance our knowledge of the ongoing drug
development processes in the treatment of hepatitis B and
hepatitis C and other viruses affecting the liver, including
co-infections with HIV. HEP DART 2013 will uniquely
blend the areas of biology, chemistry, pharmacology and
clinical research to provide the scientific community with
an increased understanding of the current and future
challenges in therapeutics for hepatitis infection.”
There were a wide array of presentations on both
HCV and HBV, but we choose to focus on 3 presentations that address the epidemiology and needs of people
are risk for or living with HCV who are often forgotten:
people who inject drugs (PWIDs) and people in prison.
Addressing Health Disparities in HCV:
The “Forgotten Populations”
In August 2012, the CDC released recommendations for
screening HCV infection in people born between 1945 and
1965 — so-called “baby boomers”. Initially, the United
States Preventative Services Task Force did not endorse
these recommendations, but a concerted effort from advocates helped to overturn that decision. Lost in the excitement of these recommendations was the fact the USPSTF
also endorsed the screening of HCV in “risk-based populations”: PWIDs, non-injection nasal drug-users, and prisoners. Dr. Mark Sulkowski of Johns Hopkins University
School of Medicine delivered a provocative presentation
entitled the “Forgotten Populations” reminding us of the
other people who at risk for or living with HCV, as well as
other subgroups with special needs in the US.
The global burden of viral hepatitis is high: hepatitis B and C deaths are slightly less than those of HIV,
but on par with malaria, road accidents and non-HIV
related tuberculosis. In low and middle income countries, particularly in the Middle East and Southeast Asia,
the burden of HCV is high and often in genotypes that
have not been typically addressed by the pharmaceutical
industry. Genotype 3 and 4 are more common in these
countries than they are in high income countries, but research for them and available treatments are lacking. By
contrast, for example, while much research and development has occurred for treating and curing HCV GT1 (the
most common in the US and Europe), and we are seeing
cure rates in the 90-100% range, with shorter duration of
treatments and fewer side effects.
In the US, HCV screening in HIV-infected persons
— and now in those born between 1945 and 1965 — are
recognized and practiced routinely. Sulkowski lists the
following populations as “forgotten”: prisoners, persons
who inject drugs, African Americans, persons born after 1965 and persons born before 1965. Sulkowski notes
that even in areas where it is widely recognized that HCV
disease is a significant burden, such as in PWIDs, there
are limited options for screening, care and treatment.
Similarly, while it is widely accepted that the burden of
HCV falls disproportionately among African Americans,
health disparities in this population continue.
Dr. Sulkowski highlighted the importance of screening for HCV in pregnant women citing the fact the USPSTF will not recommend routine screening for this population because there is no intervention that has been
shown to reduce the risk of transmission from mother to
infant. Rates of mother-to-child transmission are around
4.3%, and it is estimated that between 10,000 and 60,000
babies will be infected with HCV each year. Treatment as
prevention in this population may be an option as we are
now in an era where ribavirin — a drug that is contraindicated for pregnancy — is unnecessary. More research
is needed, but the early results of safety testing of sofosbuvir have been promising in animal modeling.
Dr. Sulkowski’s presentation also highlighted an
emerging problem in HCV: A rise of infections in non-
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
urban youth who inject drugs. We have seen reports in
Massachusetts and New York of outbreaks of acute HCV
infections in this population. These youth often begin
with prescription opioid use and move on to injecting
heroin. There are limited services targeting this group,
and as HCV is often asymptomatic these new infections
often go unrecognized and other transmissions occur as
they share injecting equipment. As we move further into
the era of direct acting antivirals, treatment as prevention may also serve us in this population as well. All oral,
interferon-free treatments that are easy to take, have
fewer side effects and shorter duration can open up the
HCV treatment landscape for people who are actively using drugs, or who have recently quit use.
Finally, Dr. Sulkowski highlighted the need to screen
and treat those who were born before 1945, and therefore
fall outside the baby-boomer birth cohort recommendations. People in this age group have similar risk factors,
and comparatively higher rates of HCV infection than the
general population. Additionally, due to their age, they are
at great risk of developing end-stage liver disease such as
liver cancer. Earlier research has shown that older individuals respond to treatment as well as do younger ones,
and as we have easier treatments in the future, this trend
should continue. A one-time HCV screen for this population is an important intervention to mitigate the suffering
caused by liver cancer and other end-stage liver disease.
This presentation highlights that while we have made
much progress in the advancement of HCV treatments,
we have far to go in the arena of screening and linkage to
care and treatment. Similarly, we must do a better job of
preventing HCV in vulnerable populations such as young
people who inject drugs, as well as in mother-to-child
transmission. The hope is that with these newer, easier to
take treatments, these populations will have their needs
met; but public health officials, clinicians and advocates
must stay vigilant and not assume that this will happen
without effort.
SOURCE:
Sulkowski, M. Forgotten Populations (Hepatitis C). HEP
DART 2013. Big Island, Hawaii, December 8-12, 2013.
|
w w w. p r o j ec t i n fo r m .o r g
10
Breaking Down the Barriers to HCV Treatment
among People Who Inject Drugs
Treating hepatitis C in people who inject drugs (PWID) is
a very important issue, yet it remains a very controversial
one among many in the public health and medical communities. In this presentation, Jason Grebely of the University of New South Wales, Australia, provides a broad
overview of this issue and demonstrates the importance
of reaching this population, as he writes “PWID are the
core of the HCV epidemic and ‘aging cohorts’ of PWID
will lead to considerable advanced liver disease burden.”
PWID make up about 80% of new infections and
60% of all infections overall, and HCV is a leading cause
of death in this group. Grebely shows us that 80% PWID
are willing to do HCV treatment, yet only 1-2% per year
receives treatment. He reviews a number of barriers at
three distinct, but inter-related levels: systems, provider
and patient.
At a systems-level there is limited infrastructure for
the screening, care and treatment of PWID, a lack of
standard recommendations for screening and treatment,
and in some case, no or limited mechanisms to cover the
cost of treatment. Providers have concerns about treating PWID due to fears of poor adherence to treatments,
inability to manage side effects, or risk of reinfection if
successfully cured. Finally, patients are hampered by
competing priorities of substance use and other basic
survival needs (housing, employment, etc) as well having
limited knowledge of HCV, including understating the
seriousness of the disease.
In spite of these barriers, Grebely’s presentation reviewed 36 academic papers and found high rates of sustained virologic response (SVR, the term used to describe
a cure for HCV) in a number of studies, and an SVR rate
of over 55% overall (with the treatment standard of care
on pegylated interferon and ribavirin). Certainly treatment is not easy, and Grebely reviews strategies to improve HCV screening, assessment and treatment for
PWID, among them access to point of care rapid HCV
testing, enhanced education programs, participation in
support groups and a multidisciplinary approach to HCV
treatment.
Finally, Grebely closes with a discussion of the broader, public health impact of treating PWID: Treatment as
prevention. Estimates suggest that as we scale-up treat-
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
ment for PWID, we will not only reduce the prevalence
of HCV (that is, the number of people living with the disease), but we will also see a decrease of HCV incidence
(that is, of new HCV infections). This has implications in
a variety of settings, including jails and prisons, as treating populations who are most at risk will significantly
lower new infections in the future.
SOURCE:
Grebely, J. Breaking Down the Barriers to HCV Treatment among People Who Inject Drugs. HEP DART 2013.
Big Island, Hawaii, December 8-12, 2013.
HCV Treatment in Prisons
Just as reaching and treating people who inject drugs
will be vital to addressing HCV in the US, so too will
reaching and treating people in jails or prisons. The US
has the largest prison population in the world, and most
have a history of substance use. Overall, 17% of inmates
in US jails or prisons are HCV antibody positive, with
12% chronically infected — although only about 25% are
aware of their infection. It is estimated that over 1 million
people with HCV come into contact with the US criminal justice system each year. Indeed, incarcerated people
represent as many as 1/3 of the US HCV-infected population. Liesl Hagan, an MPH student at Emory University,
presented on the cost effectiveness of treating people in
prison in the era of direct acting antivirals.
Previous studies have shown that interferon-free
HCV regimens are cost-effective when compared to the
previous standard of care in the community. Hagan
based her cost-effectiveness analysis of treating in prisons based on the cost of treatment and the benefits of
such treatment using a measure called “Quality Adjusted
Life Years” (QALYs). She found that treating people in
prison with interferon-free therapy was more cost effective than in the community. The cost effectiveness
increased further when younger prisoners were treated,
and if/when HCV drug prices go down the cost effectiveness increases further.
These are important findings for public health officials and prisoner health advocates. Treating prisoners
with HCV has important public health implications and
can cure up to 1/3 of people living with HCV. Hagan con-
|
w w w. p r o j ec t i n fo r m .o r g
11
cludes her presentation with a call to “invest in high-risk,
high prevalence populations” with the impact of not only
improving prisoner health, but reducing the risk of transmission both within the prison system itself, and the communities in which people in prison will eventually return.
SOURCE:
Hagan, L. Optimizing Cost-Effectiveness of All-Oral
Hepatitis C Treatment in Prison Settings. HEP DART
2013. Big Island, Hawaii, December 8-12, 2013.
CONFERENCE: ID Week
ID Week is a relatively new conference that brings together infectious disease specialists and researchers
from a wide array of disciplines and interests. Hepatitis
C was featured in a variety of presentations, and we highlight two of them here.
HCV Deaths Severely Under-represented
in the United States
Official statistics state that between 2.7 to 3.9 million
people are living with chronic hepatitis C (HCV), making
it the most common blood-born infection in the US, and
a leading cause of death and liver transplants. However,
there are many who think our knowledge of the true number of people living with HCV is severely under-reported,
as is our knowledge of the actual number of deaths related to this disease. Following a review of data from the
Chronic Hepatitis Cohort Study (CHeCS), Reena Mahajan and colleagues conclude that HCV-related deaths are
indeed grossly under-reported and the mortality rate for
people infected with HCV is 12 times higher than that of
the general public.
The authors looked at 11,703 patients in CHeCS, a
longitudinal observational cohort study of over 2.1 million people infected with chronic HCV. Within this group,
1,590 HCV patients died during the study period, 2006
to 2010. At the same time they compared these deaths
with the deaths of 12 million people from the “Multiple
Cause of Death”.
In their analysis, the authors found that HCV listed
as the cause of death was extremely low and leads to an
P r o j e c t i n f o r m PERSPECT I VE
|
SEPTEM B ER 2 0 1 3
underestimation of the actual cause of death in many
people living with HCV. Even among the 1,590 patients
in CHeCS who died during the study period, only 19%
had HCV listed on their death certificate. Overall 16,622
people had HCV listed on their death certificates in 2010,
the actual number was more likely to be over 80,000.
The mortality rate from HCV was 12 times higher than
that of the general population. The mean age of death in
people with HCV was 59 years, while that of the general
population was 74.
As we enter the era of “direct acting antivirals”, we
have the potential to dramatically reduce the number of
deaths from hepatitis C. This study highlights the need
for effective screening, identification and treatment of
HCV in order for the United States to reduce the burden
of disease and suffering caused by hepatitis C.
SOURCE:
Mahajan, R., et al. Mortality among Persons in Care
with Hepatitis C Virus Infection-Chronic Hepatitis Cohort Study (CHeCS), 2006-2010. ID Week, 2013, San
Francisco, CA. October 2-6, 2013.
Referral and Treatment Patterns of
Chronic Hepatitis C
Screening and linkage to care can be a challenge for people
with HCV, and this poster presentation illustrates some
these challenges, but also points to potential successes.
In a retrospective cross-sectional study looking at HCVinfected persons in a community-based clinic, Dr. Wei B.
Ooi and colleagues found that 215 of 235 (92%) of patients
|
w w w. p r o j ec t i n fo r m .o r g
12
who test positive for HCV were referred to a hepatitis
specialist. The authors hypothesized that this was due to
an integrated electronic medical record and a sharing of
some staff across programs. The success of the referral,
however, did not lead to immediate linkage to care or HCV
treatment. Out of these 215 patients, only 146 (68%) saw a
specialist and only 26 of these individuals (18%) received
treatment. Additionally, the average time from referral to
actually seeing a specialist was 411 days, and the average
time of referral to treatment was 226 days.
The authors found several facilitators and barriers to
care. Among the facilitators, those who were co-infected
with HCV and HIV, had other non-HCV related morbidity, or were married were more likely to receive earlier HCV
care. The barriers included active substance use, mental
health disorders and/or patient preference to defer care.
The authors conclude that the low rate of treatment
initiation is the result of a complex array of patient, provider and/or system factors. This is a very important
study that highlights a vexing problem for HCV: Even
as we are advancing the HCV treatment landscape to include simpler, shorter and more effective medications,
we still have far to go with screening and linkage to care.
Further research into effective techniques and methods
of referral and linkage will add to our understanding of
the complexities of engaging HCV-infected patients into
medical care and should be prioritized going forward.
SOURCE:
Ooi, W, et al. Referral and Treatment Patterns of Chronic Hepatitis C. ID Week, 2013, San Francisco, CA. October 2-6, 2013.