JAMA: With there being a need for interferon-free treatment because of
potential toxicities for patients with hepatitis C virus (HCV) and human
immunodeficiency virus 1 (HIV-1), two studies appearing in JAMA
using interferon-free drug regimens resulted in high rates of sustained
virologic response, which is a lack of detectable HCV RNA at least 12
weeks after completion of treatment.
Hepatitis C virus and HIV-1 co-infections are common because of
similar routes of transmission, including injection drug use, blood
transfusion, or sexual contact. Since the advent of effective
antiretroviral therapy, liver-related disease has emerged as a leading
cause of illness and death in HCV/HIV-1 co-infected patients, who are at
greater risk for progression to liver cirrhosis and hepatitis or
liver-related death than individuals with HCV and not HIV-1.
Interferon-based treatments for HCV infection have significant
toxicities, limiting their use; a significant unmet need exists for a
highly efficacious, interferon-free treatment. Mark S. Sulkowski, M.D.,
of Johns Hopkins University, Baltimore, and colleagues assessed the
three oral direct-acting antiviral (3D) regimen of ombitasvir,
paritaprevir (co-dosed with ritonavir [paritaprevir/r]), dasabuvir, and
ribavirin in 63 HCV genotype 1-infected adults with HIV-1 co-infection,
including patients with cirrhosis, randomly assigned to either 12 or 24
weeks of treatment. The patients had not received prior HCV treatment or
had history of prior treatment failure with peginterferon plus
ribavirin therapy. The study was conducted at 17 sites in the United
States and Puerto Rico between September 2013 and August 2014.
Plasma HCV RNA suppression was rapid in patients receiving 3D plus
ribavirin; 58 of 63 patients (92 percent) had an HCV RNA below the lower
limit of quantitation at treatment week 2; after 12 or 24 weeks of
treatment with 3D plus ribavirin, 29 of 31 patients (94 percent) and 29
of 32 patients (91 percent) achieved SVR12 (sustained virologic response
at posttreatment week 12), respectively; the difference between
treatment groups was not statistically significant.
The most common treatment-emergent adverse events were fatigue (48
percent), insomnia (19 percent), nausea (18 percent), and headache (16
percent).Adverse events were generally mild, with none reported as
serious or leading to discontinuation of treatment.
“In this open-label, randomized uncontrolled study, treatment with
the all-oral, interferon-free 3D-plus-ribavirin regimen resulted in high
SVR rates among patients co-infected with HCV genotype 1 and HIV-1
whether treated for 12 or 24 weeks. Further phase 3 studies of this
regimen are warranted in coinfected patients,” the authors write.
(doi:10.1001/jama.2015.1328; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor’s Note:
This trial was funded by AbbVie. Please see the article for additional
information, including other authors, author contributions and
affiliations, financial disclosures, etc.
==========================================
In another study, Shyam Kottilil, M.D., Ph.D., of the University of
Maryland School of Medicine and the Institute of Human Virology,
Baltimore, and colleagues evaluated the rates of SVR following a
treatment regimen of the antiviral agents ledipasvir and sofosbuvir in
50 patients co-infected with HCV genotype 1 and HIV who were never
before treated for HCV. The patients, who did not have cirrhosis, were
prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir
(400 mg) once daily for 12 weeks. The study was conducted from June
2013 to September 2014 at the Clinical Research Center of the National
Institutes of Health.
Forty-nine of 50 participants (98 percent) achieved sustained viral
response 12 weeks after the end of treatment. One patient experienced
relapse at week 4 following treatment; further analysis indicated a
genetic mutation associated with resistance to inhibitors such as
ledipasvir.
The most common adverse events were nasal congestion (16 percent of
patients) and myalgia (14 percent; pain in the muscles or within muscle
tissue). There were no discontinuations or serious adverse events
attributable to the study drug.
“In this open-label, uncontrolled, pilot study enrolling patients
co-infected with HCV genotype 1 and HIV, administration of an oral
combination of ledipasvir and sofosbuvir for 12 weeks was associated
with high rates of SVR after treatment completion. Larger studies that
also include patients with cirrhosis and lower CD4 T-cell counts are
required to understand if the results of this study generalize to all
patients co-infected with HCV and HIV,” the authors write.
“These results show for the first time, to our knowledge, that an
interferon- and ribavirin-free therapy is associated with high SVR rates
in patients co-infected with HCV and HIV.”
(doi:10.1001/jama.2015.1373; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor’s Note:
Please see the article for additional information, including other
authors, author contributions and affiliations, financial disclosures,
funding and support, etc.
Editorial: Hepatitis C and HIV Co-infection
Camilla S. Graham, M.D., M.P.H., of the Beth Israel Deaconess Medical
Center, Boston, comments on the findings of these studies in an
accompanying editorial.
“Liver disease represents the second leading cause of death in
persons infected with HIV. The high SVR rates in these 2 studies suggest
that future barriers to prevention of unnecessary deaths due to HCV may
be related to failures of the health care system. Clinicians who care
for patients with HIV infection are already skilled at selecting
regimens, managing drugdrug interactions, optimizing adherence, and
providing harm reduction counseling. These skills are exactly what is
needed to treat patients with hepatitis C and to ensure that the
successes seen in research trials are replicated in clinical practice.”
“Many clinicians also have experience advocating for their patients,
and this skill may be as valuable now as it was in the early days of
HIV. With the current concern about the high price of these regimens, it
is critical that the patients who are living with hepatitis C and the
value of treating this disease remain front and center.”
(doi:10.1001/jama.2015.1111; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor’s Note:
The author has completed and submitted the ICMJE Form for Disclosure of
Potential Conflicts of Interest and none were reported.
Previous Related Content From JAMA: Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Co-infection (July 23/30, 2014); available at this link: http://ja.ma/1ESyOWw