12 Weeks of Daclatasvir in Combination With Sofosbuvir for HIV-HCV Coinfection (ALLY-2 Study): Efficacy and Safety by HIV Combination Antiretroviral Regimens

Abstract

Background: Highly effective hepatitis C virus (HCV) direct-acting antiviral therapies that do not require modification of human immunodeficiency virus (HIV) antiretroviral regimens are needed. We evaluated the efficacy and safety of daclatasvir + sofosbuvir (DCV + SOF) for 12 weeks by antiretroviral (ARV) regimen in HIV-HCV-coinfected patients.

Methods: In the randomized, open-label ALLY-2 study, HIV-HCV-coinfected patients received 8 or 12 weeks of once-daily DCV 60 mg (dose-adjusted as-necessary for concomitant ARVs) + SOF 400 mg. Results were stratified by ARV class for the 151 patients who received 12 weeks of DCV + SOF.

Results: Fifty-one patients were HCV treatment experienced, 100 were treatment naive, 89% male and 33% black. HCV genotypes were: genotype 1a (GT1a; 69%), GT1b (15%), GT2 (8%), GT3 (6%), and GT4 (2%). Sustained virologic response 12 weeks post-treatment (SVR12) was 97% and was similar across ARV regimens (P = .774): protease inhibitor-based, 97% (95% confidence interval [CI], 90%-99.7%); nonnucleoside reverse transcriptase inhibitor-based, 100% (95% CI, 91%-100%); and integrase inhibitor based, 95% (95% CI, 83%-99.4%). SVR12 among patients receiving either tenofovir disoproxil fumarate or abacavir as part of their antiretroviral therapy regimen was 98% (95% CI, 93%-99.5%) and 100% (95% CI, 85%-100%), respectively. Age, gender, race, cirrhosis, HCV treatment history, GT , and baseline HCV RNA did not affect SVR12. No discontinuations were attributed to treatment-related adverse events.

Conclusions: DCV + SOF x12 weeks is a highly efficacious, all-oral, pan-GT HCV treatment for HIV-HCV coinfected patients across a broad range of ARV regimens.

Clinical trials registration: NCT02032888.

Keywords: HIV-HCV; antiretroviral therapy; coinfection; daclatasvir; sofosbuvir.

Figure 1.

Sustained virologic response 12 weeks post-treatment (SVR12) by antiretroviral therapy. (a) The 60-mg standard dose of daclatasvir (DCV) was adjusted to 30 mg with ritonavir-boosted (/r) protease inhibitors. Recent data suggest that a 60-mg dose of DCV should be coadministered with darunavir/r or lopinavir/r [15]. (b) Two patients on protease inhibitors had hepatitis C virus (HCV) relapse. (c) One patient was lost to follow-up at week 6 due to incarceration; 1 nonadherent patient with detectable HCV RNA at end of treatment received approximately 1 week of treatment. Abbreviations: CI, confidence interval; INSTI, integrase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Figure 2.

A, Sustained virologic response 12 weeks post-treatment (SVR12) by patient demographics. B, SVR12 by baseline disease characteristics. C, SVR12 by hepatitis C virus (HCV) genotype (GT) at baseline. (a) Two patients were taking nucleoside reverse transcriptase inhibitors only. (b) GT2, n = 3; GT3, n = 4. (c) GT2, n = 5; GT3, n = 4; GT4, n = 1. (d) GT2, n = 4; GT3, n = 1; GT4, n = 2. (e) IL28B TT: 16/16. (f) IL28B TT: 12/12. (g) IL28B TT: 6/6. Abbreviations: CI, confidence interval; INSTI, integrase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Figure 3.

CD4 cell counts during treatment. Abbreviations: INSTI, integrase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; SD, standard deviation.