HIV/HCV therapy with ledipasvir/sofosbuvir after randomized switch to emtricitabine-tenofovir alafenamide-based single-tablet regimens

Abstract

Introduction: Guidelines advocate the treatment of HCV in all HIV/HCV co-infected individuals. The aim of this randomized, open-label study (ClinicalTrials.gov identifier: NCT02707601; https://ichgcp.net/clinical-trials-registry/NCT02707601) was to evaluate the safety/efficacy of ledipasvir/sofosbuvir (LDV/SOF) co-administered with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/F/TAF (R/F/TAF) in HIV-1/HCV co-infected participants.

Methods: Participants with HIV-1 RNA <50 copies/mL and chronic HCV-genotype (GT) 1 (HCV treatment-naïve ± compensated cirrhosis or HCV treatment-experienced non-cirrhotic) were randomized 1:1 to switch to E/C/F/TAF or R/F/TAF. If HIV suppression was maintained at Week 8, participants received 12 weeks of LDV/SOF. The primary endpoint was sustained HCV virologic response 12 weeks after LDV/SOF completion (SVR12).

Results: Of 150 participants, 148 received ≥1 dose of HIV study drug and 144 received LDV/SOF (72 in each F/TAF group; 83% GT1a, 94% HCV treatment-naïve, 12% cirrhotic). Overall, SVR12 was 97% (95% confidence interval: 93-99%). Black race did not affect SVR12. Of four participants not achieving SVR12, one had HCV relapse, one had HCV virologic non-response due to non-adherence, and two missed the post-HCV Week 12 visit. Of 148 participants, 96% receiving E/C/F/TAF and 95% receiving R/F/TAF maintained HIV suppression at Week 24; no HIV resistance was detected. No participant discontinued LDV/SOF or E/C/F/TAF due to adverse events; one participant discontinued R/F/TAF due to worsening of pre-existing hypercholesterolemia. Renal toxicity was not observed in either F/TAF regimen during LDV/SOF co-administration. In conclusion, high rates of HCV SVR12 and maintenance of HIV suppression were achieved with LDV/SOF and F/TAF-based regimens.

Conclusion: This study supports LDV/SOF co-administered with an F/TAF-based regimen in HIV-1/HCV-GT1 co-infected patients.

Conflict of interest statement

GH has received grants from Gilead, ViiV Healthcare, Janssen and Proteus and has been a scientific advisor for Gilead, ViiV Healthcare, Janssen and Theratechnologies. MR is a speaker for Gilead, Janssen, and AbbVie and has participated in advisory boards/has consulted for Gilead and Merck. MJ receives research funding from Gilead, Janssen, Merck, and GSK/ViiV Healthcare, and has participated in advisory boards for GSK. FH has received grant/research support from AbbVie, Gilead, and Janssen, and has participated in sponsored lectures for AbbVie, Gilead, Janssen, and Merck. DA has participated on a speaker board for Gilead, Merck, and Janssen as well as advisory boards for Gilead, GSK/ViiV Healthcare, and Napo Pharmaceuticals. JS has participated in speaker bureaus for Gilead, Merck, AbbVie, and Janssen. DG participated in an advisory board for Gilead. SA is an advisor and speaker for Gilead and Merck. JR, SJ, SC, MD, DP, BG, LR, and RH are employees of Gilead and hold stock interests in the company. TN-C was an employee at Gilead Sciences during the conduct of the study. He is currently an employee at Arena Pharmaceuticals, San Diego, CA, USA. The study was funded by Gilead Sciences, Inc., Foster City, CA, USA. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Disposition of participants.

AE, adverse event; E/C/F/TAF, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide; LDV/SOF, ledipasvir/sofosbuvir; R/F/TAF, rilpivirine/ emtricitabine/tenofovir alafenamide; SVR, sustained virologic response.

Fig 2. Main HCV and HIV-related efficacy outcomes.

(A) SVR12 overall (primary endpoint) and according to race, HIV TAF regimen, HCV treatment history, and cirrhosis status. (B) HIV virologic outcome (HIV RNA ≤50 copies/mL) at Week 24 by FDA-defined snapshot algorithm. CI, confidence interval; E/C/F/TAF, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide; R/F/TAF, rilpivirine/ emtricitabine/tenofovir alafenamide; SVR12, sustained virologic response 12 weeks post-HCV treatment; TAF, tenofovir alafenamide.

Fig 3

Renal safety as measured by eGFRCGa(A), urine albumin to creatinine ratiob(B), urine RBP to creatinine ratiob(C), and urine beta-2-microglobulin to creatinine ratioc(D) plotted as % change from baseline over time by TAF regimen.aFor eGFRCG, measurements were taken from 74 versus 74 patients at baseline and 72 versus 69 patients at the Post-HCV W12 visit in the E/C/F/TAF group versus R/F/TAF groups, respectively. bFor UACR and for urine RBP to creatinine ratio, measurements were taken from 73 versus 74 patients at baseline and 71 versus 69 patients at the Post-HCV W12 visit in the E/C/F/TAF group versus R/F/TAF groups, respectively. cFor urine B2M to creatinine ratio, measurements were taken from 73 versus 72 patients at baseline and 72 versus 68 patients at the Post-HCV W12 visit in the E/C/F/TAF group versus R/F/TAF groups, respectively. BL, baseline; B2M, beta-2-microglobulin; CR, creatinine ratio; E/C/F/TAF, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide; eGFR, estimated glomerular filtration rate; eGFRCG, estimated glomerular filtration rate calculated using the Cockcroft–Gault equation; LDV/SOF, ledipasvir/sofosbuvir; Q, quartile; RBP, retinol binding protein; R/F/TAF, rilpivirine/emtricitabine/tenofovir alafenamide; TAF, tenofovir alafenamide; UACR, urine albumin to creatinine ratio; W, week.