Background: There is a need for HCV direct-acting antiviral therapies that are compatible with the most commonly used HIV combination antiretroviral therapies (cART). The all-oral, pangenotypic, once-daily combination of daclatasvir (DCV) and sofosbuvir (SOF) for 12 weeks achieved a sustained virologic response (SVR) of 97% in HIV/HCV coinfected patients. DCV+SOF was well tolerated and had a favorable drug-drug interaction profile across a broad range of cART.
Methods: In the randomized, open-label ALLY-2 study, HIV/HCV coinfected patients with creatinine clearance > 50 mL/min received either 8 or 12 weeks of once-daily SOF 400mg + DCV 60mg (with dose adjustment for cART: 30mg with ritonavir-boosted PIs, 90mg with NNRTIs except rilpivirine [60mg]). Here we present efficacy and safety results, stratified by cART class, for the 151 patients (HCV treatment-naive, n=100; -experienced, n=51) who received 12 weeks of DCV+SOF and cART in ALLY-2.
Results: Eighty-nine percent of patients were male, 64% were white, and 32% were black. The median baseline HCV viral load was 6.7×106 IU/mL and median CD4 count was 557 cells/mm3. SVR12 rates were high regardless of NRTI backbone (tenofovir, 98% [n=113/115]; abacavir, 100% [n=23/23]) or cART regimen (PI-, 97%; NNRTI-, 100%; INSTI-based, 95%) and were unaffected by age, gender, race, presence of cirrhosis, prior treatment status, HCV genotype, baseline HCV viral load or CD4 count (Table). HIV virologic control was maintained throughout the study and there were no HIV-related opportunistic infections. There were no treatment-related serious AE or AEs leading to discontinuation. The most common AEs (≥10% overall) were fatigue (19%), nausea (14%), and headache (13%). PI recipients experienced most of the treatment-emergent grade 3/4 laboratory abnormalities (n=12/16; total bilirubin, n=8 [all receiving ATV/r]; INR, n=2; lipase, n=2). There were no grade 3/4 changes in creatinine.
Conclusion: DCV+SOF once daily for 12 weeks is highly efficacious and well tolerated for the treatment of HCV in HIV/HCV coinfected patients. High SVR rates (97%) were achieved across a broad range of commonly used cART with no compromise in HIV virologic control.
Bristol Myers Squibb:
Abbvie: Grant Investigator , Grant recipient
Gilead: Grant Investigator , Research grant
Pfizer: Grant Investigator , Research grant
Merck: Grant Investigator , Grant recipient
ViiV: Investigator and Speaker's Bureau , Research support
BMS: Investigator and Speaker's Bureau , Research support
Merck: Investigator , Research support
Janssen: Investigator , Research support
M. Ramgopal, Bristol Myers Squibb: Speaker's Bureau , Speaker honorarium
Gilead: Speaker's Bureau , Speaker honorarium
Cubist: Speaker's Bureau , Speaker honorarium
Abbvie: Speaker's Bureau , Speaker honorarium
ViiV: Speaker's Bureau , Speaker honorarium
Merck: Consultant , Consulting fee
S. Noviello, Bristol Myers Squibb: Employee , Salary
Merck/Schering-Plough: Employee and Shareholder , Salary
J&J: Shareholder , Stocks
R. Bhore, Bristol Myers Squibb: Employee , Salary
P. Ackerman, Bristol Myers Squibb: Employee , Salary
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