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

Anne F Luetkemeyer, Cheryl McDonald, Moti Ramgopal, Stephanie Noviello, Rafia Bhore, Peter Ackerman, Anne F Luetkemeyer, Cheryl McDonald, Moti Ramgopal, Stephanie Noviello, Rafia Bhore, Peter Ackerman

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.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
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.
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.
Figure 3.
CD4 cell counts during treatment. Abbreviations: INSTI, integrase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; SD, standard deviation.

References

    1. Bica I, McGovern B, Dhar R et al. . Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 2001; 32:492–7.
    1. Centers for Disease Control and Prevention. HIV and viral hepatitis factsheet. 2014. Available at: Accessed August 2015.
    1. Sulkowski MS, Benhamoi Y. Therapeutic issues in HIV/HCV-coinfected patients. J Viral Hepat 2007; 14:371–86.
    1. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Available at: Updated April 2015. Accessed November 2015.
    1. European AIDS Clinical Society. Guidelines Version 8.0. October 2015. Available at: Accessed November 2015.
    1. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol 2015; 63:199–236.
    1. Cope R, Pickering A, Glowa T et al. . Majority of HIV/HCV patients need to switch antiretroviral therapy to accommodate direct acting antivirals. AIDS Patient Care STDS 2015; 29:379–83.
    1. Viekira Pak® (ombitasvir, paritaprevir and ritonavir tablets; dasabuvir tablets). US prescribing information. Abbvie 2014. Available at: Accessed October 2015.
    1. Harvoni® (ledipasvir and sofosbuvir). US prescribing information. Foster City, CA: Gilead Sciences, 2015. Available at: Accessed December 2015.
    1. Sovaldi® (sofosbuvir) US prescribing information. Foster City, CA: Gilead Sciences, 2013. Available at: Accessed December 2015.
    1. Bifano M, Hwang C, Oosterhuis B et al. . Assessment of pharmacokinetic interactions of the HCV NS5A replication complex inhibitor daclatasvir with antiretroviral agents: ritonavir-boosted atazanavir, efavirenz and tenofovir. Antivir Ther 2013; 18:931–40.
    1. Sulkowski MS, Gardiner DF, Rodriguez-Torres M et al. . Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014; 370:211–21.
    1. Wyles DL, Ruane PJ, Sulkowski MS et al. . Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med 2015; 373:714–25.
    1. Torriani FJ, Rodriguez-Torres M, Rockstroh JK et al. . Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004; 351:438–50.
    1. Gandhi Y, Adamczyk R, Wang R et al. . Assessment of drug–drug interactions between daclatasvir and darunavir/ritonavir or lopinavir/ritonavir. Rev Antiviral Ther Infect Dis 2015; 4:Abstract 80 Available at: Accessed September 2015.
    1. Zeuzem S, Ghalib R, Reddy KR et al. . Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis c virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med 2015; 163:1–13.
    1. Naggie S, Cooper C, Saag M et al. . Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med 2015; 373:705–13.
    1. Sulkowski MS, Eron JJ, Wyles D et al. . Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA 2015; 313:1223–31.
    1. Eley T, You X, Wang R et al. . Daclatasvir: overview of drug-drug interactions with antiretroviral agents and other common concomitant drugs. GAJ 2014; 10(suppl 1):54–5.
    1. Reyataz® (atazanavir). US prescribing information. Princeton, NJ, Bristol Myers Squibb, 2014. Available at: Accessed October 2015.
    1. Kirby B, Mathias A, Rossi S et al. . No clinically significant pharmacokinetic drug interactions between sofosbuvir (GS-7977) and HIV antiretrovirals atripla, rilpivirine, darunavir/ritonavir, or raltegravir in healthy volunteers. AASLD 2012. Abstract: 1877.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner