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.
In another study, Shyam Kottilil, M.D., Ph.D., of the University of Maryland, 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.”
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.”
Study 1: Ombitasvir, Paritaprevir Co-dosed With Ritonavir, Dasabuvir, and Ribavirin for Hepatitis C in Patients Co-infected With HIV-1 A Randomized Trial, Mark S. Sulkowski, MD; Joseph J. Eron, MD; David Wyles, MD; Roger Trinh, MD; Jay Lalezari, MD; Chia Wang, MD; Jihad Slim, MD; Laveeza Bhatti, MD; Joseph Gathe, MD; Peter J. Ruane, MD; Richard Elion, MD; Fritz Bredeek, MD; Robert Brennan, MD; Gary Blick, MD; Amit Khatri, PhD; Krystal Gibbons, BS; Yiran B. Hu, MS; Linda Fredrick, MS; Gretja Schnell, PhD; Tami Pilot-Matias, PhD; Rakesh Tripathi, MS; Barbara Da Silva-Tillmann, MD; Barbara McGovern, MD; Andrew L. Campbell, MD; Thomas Podsadecki, MD, JAMA, doi:10.1001/jama.2015.1328, published 23 February 2015.
This trial was funded by AbbVie. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Study 2: Virologic Response Following Combined Ledipasvir and Sofosbuvir Administration in Patients With HCV Genotype 1 and HIV Co-infection, Anu Osinusi, MD, MPH; Kerry Townsend, BA; Anita Kohli, MD, MS; Amy Nelson, RN; Cassie Seamon, RN; Eric G. Meissner, MD, PhD; Dimitra Bon, MS; Rachel Silk, RN; Chloe Gross, RN; Angie Price, NP; Mohammad Sajadi, MD; Sreetha Sidharthan, BS; Zayani Sims, BS; Eva Herrmann, PhD; John Hogan, MD; Gebeyehu Teferi, MD; Rohit Talwani, MD; Michael Proschan, PhD; Veronica Jenkins, MD; David E. Kleiner, MD, PhD; Brad J. Wood, MD; G. Mani Subramanian, MD, PhD; Phillip S. Pang, MD, PhD; John G. McHutchison, MD; Michael A. Polis, MD, MPH; Anthony S. Fauci, MD; Henry Masur, MD; Shyam Kottilil, MD, PhD, JAMA, doi:10.1001/jama.2015.1373, published 23 February 2015.
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 Closing the Gaps, Camilla S. Graham, MD, MPH, JAMA, doi:10.1001/jama.2015.1111, published 23 February 2015.
The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Related content: Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Co-infection (July 23/30, 2014)