Higher relapse rate among HIV/HCV-coinfected patients receiving sofosbuvir/ledipasvir for 8 vs 12 weeks
Introduction
Hepatitis C virus (HCV) chronic infection is still a major public health problem. Recent estimations point to a global prevalence of 70 million people living with HCV chronic infection worldwide.1 Most untreated HCV-infected individuals may be soon concentrated in countries in South America, Africa, South-east Asia and Eastern Europe, because access to treatments has been more difficult in those areas, mainly due to cost issues.2 HIV infection is also highly prevalent in some specific countries of these regions3 and, in this way, both epidemics do overlap. HIV and HCV coinfection is associated with a higher risk of fibrosis progression and death due to end-stage liver disease.4, 5, 6 Thus, timely access to treatment of HIV/HCV-coinfected patients is a priority.
Sofosbuvir/Ledipasvir (SOF/LDV) is recommended as first line option to treat genotype 1 (G1) and 4-infected patients with a standard duration of treatment of 12 weeks.7, 8, 9 For G1, there is the option of shortening the length of treatment to 8 weeks, as the 8-week regimen was non-inferior to the 12-week course.10 In addition, a post-hoc analysis showed that the rate of relapse after SOF/LDV for 8 weeks was lower among individuals with baseline HCV RNA levels below 6 million UI/mL.10 Thus, current guidelines recommend a shorter duration in non-cirrhotic patients, without previous treatment experience and HCV viremia below that threshold.8, 9 A single tablet, once-daily, short-duration regimen can be particularly useful in difficult to follow populations and in low resource settings. Moreover, it is possible to retreat relapses to SOF/LDV for 8 weeks with longer courses of the same regimen with high efficacy.11 Finally, SOF/LDV is now available as generic, and therefore cheaper, medicine in countries from South America, Africa and South-east Asia.
There are limited comparative data of the efficacy and safety of SOF/LDV 8-weeks between HCV-monoinfected and HIV/HCV-coinfected individuals.12, 13 Current guidelines provide controversial recommendations for treatment with short-duration SOF/LDV in HIV/HCV coinfection. For G1, European guidelines recommend no different duration of SOF/LDV for the HCV-monoinfected or the HIV/HCV-coinfected patients,9 while USA guidelines recommend against SOF/LDV for a shortened length of time in HIV/HCV-coinfection.8 Therefore, the aim of this study was to compare the efficacy in real life setting of an 8-week SOF/LDV regimen versus a 12-week of this combination among HIV/HCV-coinfected patients. In addition, SVR rates achieved with an 8-week SOF/LDV regimen among HCV-monoinfected and HIV/HCV-coinfected patients were also compared.
Section snippets
Patients and study design
This study included patients from two prospective real-life cohorts of direct acting antiviral agents (DAA)-treated patients, conducted at 25 Infectious Diseases Units throughout Spain. In these cohorts, all subjects with HCV infection or HIV/HCV co-infection who initiated therapy with one or more DAA are followed since October 2011 (GEHEP-MONO Cohort, ClinicalTrials.gov ID: NCT02333292 and HEPAVIR-DAA Cohort, ClinicalTrials.gov ID: NCT02057003). For the present study, patients treated from
Characteristics of the study population
By September 2017, 2173 patients from the HEPAVIR and GEHEP cohorts had been treated with SOF/LDV. After excluding 1580 because not meeting the study eligibility criteria, 209 initiated SL8, and 384 received SL12. The disposition of patients is shown in Fig. 1.
The baseline characteristics of the patients, by their HIV status, receiving SL8 and SL12 are shown in Tables 1, 2 and 1supl. There was a greater proportion of men and of injecting drug users (IDU) in the HIV/HCV group. Genotype 1a was
Discussion
This study suggests that SVR12 rates with an 8-week SOF/LDV regimen are lower than with a 12-week course of this combination among HIV/HCV-coinfected patients. This is driven by a higher probability of relapse with short duration therapy. Accordingly, SVR12 rates SOF/LDV 8 weeks are numerically lower and the proportion of relapses higher in HIV/HCV-coinfected patients compared with HCV-monoinfected subjects.
In the present study, HIV/HCV-coinfected patients receiving SL8 were less likely to
Funding
This study was partly supported by the projects “PI15/01607” and “PI16/01443”, funded by Instituto de Salud Carlos III, integrated in the national I+D+i 2013-2016 and co-funded by European Union (ERDF/ESF, “Investing in your future”) and by the Grupo para el Estudio de las Hepatitis Víricas (GEHEP) (grant GEHEP 001 2017). J.M. is the recipient of a grant from the Servicio Andaluz de Salud de la Junta de Andalucía (grant number B-0037). J.A.P. is recipient of an intensification grant from the
Conflict of interest
ACG has received lecture fees from Gilead. JM has been an investigator in clinical trials supported by Bristol-Myers Squibb, Gilead and Merck Sharp & Dome. He has received lectures fees from Gilead, Bristol-Myers Squibb, and Merck Sharp & Dome, and consulting fees from Bristol Myers-Squibb, Gilead, and Merck Sharp & Dome. JAP reports having received consulting fees from Bristol-Myers Squibb, Abbvie, Gilead, Merck Sharp & Dome, and Janssen Cilag. He has received research support from
Acknowledgments
Author contributions: J.M had full access and to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: J.M and J.A.P.
Acquisition, analysis, or interpretation of data: all authors.
Statistical analysis: A.C.G and J.M.
Drafting of the manuscript: A.C.G. and J.M.
Critical revision of the manuscript for important intellectual content: all authors.
Obtained funding: J.M, and J.A.P.
Study supervision: J.M.
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