Elizabeth Boskey, Ph.D. is a Certified Health Education Specialist and A.A.S.E.C.T. Certified Sexuality Educator as well as an independent scholar, writer, and teacher focusing on sexual health.
Although she is best known as the Guide to Sexually Transmitted Diseases at About.com, where she writes a consumer-focused site about sexual health, she has been enjoying writing more in depth content for health professionals at ViroChannel.
A researcher herself, Elizabeth has published several peer-reviewed papers on topics in women’s reproductive health and is on the editorial boards of the American Journal of Sex Education and Contemporary Sexuality – the journal of the American Association of Sexuality Educators, Counselors, and Therapists.
She has also written or contributed to a number of popular science books including America Debates Genetic DNA Testing, The Truth About Rape, and The Invision Guide to Sexual Health.
This past week, scientists from across the globe gathered in Washington DC for the 64th Annual Meeting of the American Association for the Study of Liver Diseases – better known as The Liver Meeting. It was an exciting time for scientists, with new data being presented about a number of issues highly relevant to physicians currently working in the field. These ranged from a clear demonstration of the long-term benefits of liver transplantation for patients with gastroentero-pancreatic neuroedocrine tumors (GAP-NET) to new information about the efficacy of mainly interferon-free treatment regimens for hepatitis C (HCV).
For the first time, a record number of studies on fixed-dose combination treatments against HCV were presented. However, some great news was announced at this congress: physicians have been waiting for a long time for the arrival of interferon-free therapeutic combinations and the efficacy data presented was excellent.
One main focus was on new developments in HCV treatment, where numerous studies looked at the possibilities for treatment with all-oral regimens that do not include peg-interferon.
The largest study, Study 026, a Phase III study of 222 genotype 1b treatment-naïve patients in Japan, looked at the efficacy of a combined treatment of daclatasvir and andasunaprevir. They found that 88.1 percent of those patients had a sustained virologic response (SVR) by week 12, a cure rate at 12 or 24 weeks greater and achieved faster than that expected from more difficult, and less well-tolerated, peg-interferon /ribavirin/telaprevir treatments. Interferon-free combinations contain drugs that attack different stages in the HCV lifecycle, so that viral replication can be interrupted and quickly reduced, allowing rapid elimination of HCV from the liver and the blood.
A second study, called LONESTAR, comparing three different treatment methods in inner city and genotype 1a infected males (66%) found similar efficacy (SVR greater than 95% at 12 weeks) for interferon-free therapeutics. All three treatments were well tolerated and resulted in high levels of viral suppression (greater than 90%), even in the normally difficult to treat patient population. Furthermore, the study found that, although a once daily, single-pill, fixed-dose combination therapy with sofosbuvir and ledipasvir was effective in the population, adding another direct acting antiviral – GS-9451 – led to more rapid viral suppression. This could shorten treatment duration and further simplify patient management in patients who can be compliant with a multi-pill regimen. However, both single- and multi- pill regimens represented good options for treatment, depending on patient needs.
All-Oral Combination of Faldaprevir, Deleobuvir, and PPI-668 With and Without RBV Effective in Treatment-Naive HCV Genotype 1a–Infected Patients
Also looking at genotype 1a patients was this Phase II study comparing two doses of a new 3-class oral regimen, combining PPI-668 (an NS5A inhibitor) with faldaprevir and deleobuvir. Although the study was not yet complete at the time of the meeting, early results were quite promising as all patients who had competed treatment had viral loads below the limit of detection. However, it is important to note that one patient with both NS5A and NS5B substitutions experienced viral breakthrough and had to be discontinued from the study.
Other promising oral treatments coming down the pipe include a regimen combining MK-5172 (a protease inhibitor) and MK-8742 (an NS5A inhibitor) with ribavirin. C-WORTHY, an early safety and efficacy study of the regimen, showed promise in both genotype 1a and 1b patients, where all patients had undetectable viral loads by treatment week 4.
Finally, PHOTON-1 investigators released their SVR-12 data for the combination of the NS5B inhibitor sofosbuvir with ribavirin in HIV-HCV coinfected patients. They found that the regimen was well-tolerated and safe when used with a variety of HIV antiretroviral therapy regimens, although efficacy varied by hepatitis genotype. Genotype 2 and 3 coinfected patients were more likely to experience viral relapse than those patients coinfected with genotype 1. After finishing therapy, however, a number of people experienced treatment failure, resulting in SVR-12 rates of 76% for genotype 1, 88% for genotype 2, and 67% for genotype 3 ‒ substantially higher than cure rates seen in historical studies of pegylated interferon plus ribavirin. Also, sofosbuvir plus ribavirin was generally safe and well-tolerated. And of particular importance in this study, SVR-12 rates were similar to those observed in patients with HCV monoinfection.
It’s important to note that the benefits of interferon-free treatment regimens are not only reflected in SVR data. They are also reflected in an improved patient treatment experience. This can be seen in data from the AVIATOR study of multiple interferon-free regimens using combinations of three direct acting antivirals with or without ribavirin, which examined health related quality of life and patient reported outcomes. Investigators found that, unlike with earlier treatment options, interferon-free regimens seem to do a good job of preserving patient health, function, and quality of life. In other words, not only can such interferon-free regimens improve the efficacy and mechanics of treatment; they can also improve patients’ lives.
Data presented at the Liver Meeting suggests that such all-oral regimens may even simplify the management of some of the hardest to treat patients, those who have received a liver transplant.
A Phase II trial of an interferon-free treatment regimen (COSMOS) containing the oral antivirals sofosbuvir, an investigational agent, and ribavirin was able to prevent HCV recurrence in more than half of patients.
This represents a significant outcome improvement over interferon-based regimens, and provides additional hope for the benefits of treatment simplification in patients living with HCV.
To consult the abstracts and posters from AASLD 2013, visit: http://www.aasld.org/livermeeting/Pages/Liver2013.aspx