Higher relapse rate among HIV/HCV-coinfected patients receiving sofosbuvir/ledipasvir for 8 vs 12 weeks

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Highlights

  • SVR rate is lower among HIV/HCV-coinfected patients with 8 vs 12-week SOF/LDV.

  • This result is mainly driven by a higher proportion of relapses with short therapy.

  • SVR rate with 8-week SOF/LDV is lower in HIV/HCV-coinfected vs HCV-monoinfected subjects.

  • Depending on economic issues, SOF/LDV 8-week could be a cost-effective strategy.

Abstract

Objectives

To compare the efficacy of sofosbuvir/ledipasvir (SOF/LDV) for 8 weeks (SL8) versus a 12-week course of SOF/LDV (SL12) among HIV/HCV-coinfected patients in clinical practice. In addition we compared sustained virological response (SVR) rates achieved with SL8 in HCV-monoinfected and HIV/HCV-coinfected patients in a real life setting.

Methods

HCV-infected patients were retrospectively selected from the HEPAVIR-DAA and GEHEP-MONO real-life prospective cohorts if they fulfilled the following criteria: 1) Infected with genotype 1; 2) Treatment with SL8 or SL12; 3) Treatment naïve prior to receiving SL8 or SL12; 4) Absence of cirrhosis; 5) Baseline HCV RNA<6 × 106 IU/mL; 6) Reached the scheduled time-point for SVR (SVR12) assessment. SVR12 and relapse rates of HCV-monoinfected and HIV/HCV-coinfected patients were compared on an intention to treat basis. The responses with SL8 and SL12 were also compared.

Results

In the SL8 group, 107 (51%) HCV-monoinfected and 102 (49%) HIV/HCV-coinfected patients were included. One hundred and sixty-four (43%) HCV-monoinfected subjects and 220 (57%) HIV/HCV-coinfected patients received SL12. SVR12 rates for HIV/HCV-coinfected patients treated with SL8 vs SL12 were SVR12 92.2% vs. 97.3% (p = 0.044) and the respective relapse rates were 4.9% vs. 0.5% (p = 0.013). SVR12 rates for SL8 among HCV-monoinfected and HIV/HCV-coinfected patients were: 96.3% vs. 92.2% (p = 0.243), respectively. The corresponding relapse rates were 0.9% vs. 4.9% (p = 0.112).

Conclusion

HIV/HCV-coinfected patients reach high rates of SVR12 with SL8, although lower than with SL12, mainly due to a higher probability of relapse. SVR12 rates with SL8 are numerically lower and the proportion of relapses higher in HIV/HCVcoinfected patients than in HCV-monoinfected subjects.

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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