Real World Response to Direct Acting Antivirals DAA in African Americans Treated in a Non-Gastroenterology Setting

Raya Kutaimy1, Pradeep R. Kathi1, Neha Sahni1, Paul H. Naylor1, Murray N. Ehrinpreis1, Milton G. Mutchnick1

1 Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Detroit, MI, United States.

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

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Correspondence to: Paul H Naylor, Department of Internal Medicine Gastroenterology, Wayne State University School of Medicine, Detroit, MI, United States.
Email: pnaylor@gmail.com
Telephone: +39-051-2142919
Fax: +39-051-2142930

Received: April 2, 2019
Revised: April 27, 2019
Accepted: April 30, 2019
Published online: June 21, 2019


INTRODUCTION: The approval of highly effective direct acting antiviral agents such as sofosbuvir/ledipasvir (Harvoni) for the treatment of hepatitis C, provided an oral, tolerable and effective regimen with fixed dosing and treatment period. Given the large numbers of patients to be treated, it is anticipated that non-GI physicians will be treating more patients than in previous years. The goal of this study was to compare the response to Harvoni of patients treated in a Gastroenterology (GI) clinic to that of an Infectious Disease (ID)clinic./p>

METHODS: The study collected and analyzed data for HCV patients treated with Harvoni between June 2015 and December 2016 using a university physicians’ practice EMR. There were 389 patients with 294 treated by GI and 95 treated by ID./p>

RESULTS: The protocol viral clearance responses were similar for hepatitis C virus infection (HCV) patients treated in GI (93%) and ID (94%) as well as for HIV co-infected patients treated in ID (100%). The responses were similar for naïve (92%) and experienced (95%) and for both AA (93%) and non-AA (96%). Significant numbers of patients did not complete therapy (8%) or did not show up for their SVR visit (13%), thus lowering the intent to treat response compared to the protocol adherence response (97% vs 79%). The primary factor for not achieving an SVR was cirrhosis (99% vs 92%)./p>

CONCLUSIONS: ID treated significant numbers of both HIV and non-HIV HCV patients and response to treatment with Harvoni was similar to the SVR ratein the GI clinics. Our data also reflects the real-world results of Harvoni treatment where, intent to treat and per protocolare significantly different. We conclude from our study that treatment of hepatitis C with Harvoni has a high SVR without regard to physician specialty, race, HIV co-infection or previous treatment status.

Key words: Hepatitis C, viral hepatitis, direct acting anti-virals, African Americans

© 2019 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Kutaimy R, Kathi PR, Sahni N, Naylor PH, Ehrinpreis MN, Mutchnick MG. Real World Response To Direct Acting Antivirals DAA In African Americans Treated In A Non-Gastroenterology Setting. Journal of Gastroenterology and Hepatology Research 2019; 8(3): 2891-2895 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/2574


Chronic Hepatitis C CHC) affects 2.4 million people in the United States and is one of the leading causes of cirrhosis, hepatocellular carcinoma and liver transplantation[1-4]. African Americans (AA) who are more likely to be infected with hepatitis C than Caucasians, comprise 23 % of infected population, are more likely to develop hepatocellular carcinoma than non-AA populations in the United States, and are more likely to be infected with hepatitis C genotype1[5-10]. Ribavirin/Interferon based regimens were less effective in the African American population which helped to contribute to the increased numbers of AA patients with CHC[11-16]. The utilization of dual direct acting antiviral agent (DAA) combinations such as sofosbuvir/ledipasvir (Harvoni®) has provided a shift into an oral, tolerable and effective regimen with fixed dosing and treatment period[17]. (Comment: Harvoni is no longer a ‘recent’ approval) The licensing trials (ION series of clinical trials) proved high efficacy and safety of Harvoni on the treated population which included 38% African American. Subsequent real-world studies demonstrated that these high rates of efficacy with minimal side effects were also achievable in large scale treatments of AA patients treated in GI clinic settings[18-24]. Given the ease of treatment protocol, the high effectiveness, the safety profile in special populations such as HIV co-infected patients, the decline in cost and the large numbers of patients to be treated, it is likely that treatment by non-GI physicians will be required. Our aim was to evaluate the “real world” effect of Harvoni® in treating primarily African Americans infected with hepatitis C in both a Gastroenterology and non-Gastroenterology setting.


We conducted a single-center retrospective cohort study to collect and analyze data for HCV patients treated with Harvoni® by physicians in the Wayne State University Physicians Group. Patients were treated by two distinct groups of physicians, Gastroenterologists or Infectious Disease specialists, during a two-year period (January 2015-December 2016). The primary medical record search criteria were patients who were scripted and started treatment with Harvoni® during this time frame. HARVONI dosage recommendations are the same for HCV mono-infected and HCV/HIV-1 co-infected patients. All patients in this study were treated as per guidelines: 8 weeks for patients without cirrhosis and with pre-treatment HCV RNA < 6 million IU/mL, 12 weeks for  patients without cirrhosis or with compensated cirrhosis and  treatment-experienced GT 1 patients without cirrhosis,  24 weeks for  treatment experienced patients with compensated cirrhosis (ChildPugh A). Of note was the fact that ID physicians treated both HIV -HCV coinfected and mono infected HCV patients whereas GI treated primarily only patients with HCV. Chart review and data collection was performed according to Wayne State Institutional Review Board (IRB)-approved protocol. The Wayne State University Institutional Review Board operates under United States Department and Human Services Federal Wide Assurance. Demographic data such as age, sex, and race were collected for each patient included in the study. Baseline and subsequent virologic data of HCV PCR level were collected for all the patients as the primary criteria of successful treatment. While the traditional definition of SVR is a negative HCV PCR at 12 weeks after the end of treatment, the regular visits of HIV patients often resulted in the confirmation of a negative HCV at the 10 week visit rather than 12 weeks. Thus, the main endpoint of data collection was SVR(>10) which was defined as undetectable plasma HCV PCR at a visit at least 10 weeks after the end of treatment. Other assessments included end of treatment response, treatment failure and lost to follow up. A distinction was made between patients who were lost to follow up prior to the end of treatment and those who did not come back for a subsequent viral assessment after the end of treatment. Data analysis was performed using the JMP statistical program with student’s t-test for continuous variables and Pearson chi-square for character variables. Statistical significance was defined as p < 0.05.


We identified a total of 389 patients treated with Harvoni® by the Wayne State University Gastroenterology (GI) and Infectious Disease (ID) practices. There were 354 (90%) African American and 35 Non-AA patients in the study (Figure 1). Most of the patients (n = 294) were treated by GI. Patients were mainly males (73%) with a median age of 62. Co- infection with HIV was identified in 15% of the patients and they were mainly treated by the ID practice with only two patients co-infected with HIV treated by the Gastroenterology practice. The primary reason for this is that patients infected with HIV follow up regularly with the ID practice and unlike previous therapies, co-infected patients can be safely given the anti-viral therapy. Non-HIV infected CHC patients were also treated in the ID practice during this time as a result of staffing, patient volumes, and insurance authorization issues in GI. SVR (>10) per protocol was 92% and 94% for HIV negative patients treated in GI and ID practices respectively and 100% in HIV positive patients treated by ID physicians (Figure 2). Only two co-infected patients were treated in GI so their response rate (1 out of 2) is not plotted. Although the per protocol SVR (>10) was greater than 90%, the SVR(>10) with intent to treat was only 79% due to patients who were lost to follow up after they achieved an end of treatment response (ETR) (10%) or lost to follow up before the ETR visit (6.4%) (Table 1). All patients who were not lost to follow-up prior to ETR assessment, were virus negative at ETR, suggesting no viral resistance prior to treatment. Of the 11 patients who relapsed after ETR, 6 had cirrhosis (3 also had previously treated HCC and 1 had HIV), 4 did not have cirrhosis and were naïve to treatment and 1 stopped drug after 4 weeks but had an ETR. When comparing patients with and without cirrhosis, the per protocol response was lower for cirrhotic patients (92% vs 99%). When subjected to multi-variate analysis (Nominal Logistic Fit) to evaluate potential interactions, only cirrhosis achieved statistical significance. Conversely, it was rare for naïve patients who completed treatment without cirrhosis to relapse after ETR regardless of the treatment venue. Significant numbers of patients failed to return for their ETR or SVR(>10) evaluation, Thus the intent to treat values are significantly lower in the real world as compared to clinical trials.

Figure 1 Race, HIV status and treatment specialty for patients treated with ledipasvir/sofosbuvir. The numbers are posted above the bars. Majority of patients were AA (94%) and HIV-negative. They were male (73%) and had a median age of 62. The majority of patients scripted for Harvoni were treated (87%) with 9% denied due to continuing insurance issues. The x-axis indicates the HCV patient population (ie HIV-negative vs HIV positive) and the physician group treating the patients (GI=gastroenterology; ID=Infectious Diseases).

Figure 2 Sustained Virus Response weeks Post Treatment using Protocol Based Assessment. Protocol compliant patients received all of their medication and had HCV RNA measured by PCR at end of treatment (EOT) and at 10-12 weeks after treatment. The x-axis indicates the HCV patient population (ie HIV-negative vs HIV positive) and the physician group treating the patients (GI=Gastroenterology; ID=Infectious Diseases. The response was not significantly different betwee GI and ID based treatment and between HIV positive and HIV-negative patients treated in ID.

Figure 3a Categorical variables which might influence SVR protocol results. SVR(>10) vs Non-SVR(>10) for categorical variables is represented on the y=axis. The relative size of the groups represented by the width of the “bars”. The number of patients and the % are listed under the figures. All values were not significant as defined by chi-square Pearson evaluation.

Figure 3b Numerical values which might influence SVR protocol results. SVR(>10) vs Non-SVR(>10) for numerical variables are plotted on the y-axis. The number of patients and the mean and standard error of the mean (SEM) are listed under the figures. All values were not significantly different as defined by student-t test.

Table 1 Comparing Protocol to Intent to Treat.
  ProtocolIntent to Treat
  SVR*SVR (ITT)**LFT-ETR***LFT***Relapse****
GI-HIV negative 227/234=97%227/292=78%34 (11%)23 (8%)8 (3%)
ID-HIV negative34/36=94%34/39= 87%2 (5%)1 (3%)2 (5%)
GI HIV positive1/2 =50%1/2= 50%0 (0%)0 (0%)1 (50%)
ID-HIV positive47/47=100%47/56= 84%3 (5%)6 (11%)0 (0%)
Overall309/319=97%309/389 (79%)39 (10%)30 (8%)11 (3%)
*SVR=virus undetectable at least 10 weeks after end of treatment (ETR);
** ITT= intent to treat based on all patients;
*** LFT-ETR means lost to follow up after ETR visit (all patients negative at ETR visit);
**** LTF means lost to follow up prior to ETR visit;
**** Relapsed after negative ETR (1 patient did not take all medication but was ETR).

Data analysis did not show statistically significant difference in achieving SVR(>10) between African American (93%) and non-African American (96%) treated by GI or ID. Females were able to achieve higher SVR(>10) with 97% compared to 92% males but it was not significantly different by Pearson chi-Square analysis. Treatment-experienced patients who failed previous treatment (mainly with interferon based therapy) did not have a significantly different response rate than naïve patients (95% vs 92%). Patients co-infected with HIV (98% response) were not significantly different from non-HIV patients (93%).


Hepatitis C patients’ response to treatment with Harvoni® managed by ID was compared to the response of patients treated by GI. The patient population in this study was majority African American race (94%), and they completed treatment with SVR(>10) rates that was not different from our non-African American patients. This was true regardless of whether or not the patients were co-infected with HIV. Our data represent real world results of Harvoni® treatment. Response rate calculations are complicated by the high percentage of patients who were lost to follow up both during treatment (8-18%) and after their ETR visit (6-16%). While this was not surprising for non-HIV patients, the same issue was seen in the HIV co-infected patients which was unexpected.

Many of the patients were co-infected with HIV (10%), and the majority reported compliance with different regimens of anti- HIV medications and had a regular follow up with ID. HIV co-infection and treatment did not have impact on SVR(>10). Our results are similar to a retrospective study on HCV eradication in patients co-infected with HIV in Florida where treatment results did not differ in both groups, but in that study, occasional HIV virology relapse was reported either due to missed HIV treatment for a period from 5 days-2 weeks or increased HIV viral load secondary to an unspecified cause. We did not evaluate that issue in our patient population[3].

Another finding in our study was the high Harvoni® SVR(>10) rate in treatment experienced patients. There were only 55 previously treated patients out of 243 patients with an SVR(>10) protocol response assessed, and the response rate was similar to treatment naïve patients. Most were previously treated with interferon containing regimens and either did not achieve SVR or had a relapse after treatment with those regimens. Since the SVR(>10) rate was similar between treatment experienced and treatment naive, our study supports aggressively identifying and treating experienced patients who may have had the disease for a longer period of time and may be at higher risk for liver damage. This is especially important since even patients with cirrhosis are eligible for treatment with DAA therapies. The Phase 3 ION trial demonstrated similar results with > 90% SVR rate in treatment naïve and treatment experienced patients and our real word data is consistent with the clinical trials19.

We conclude from our study that treatment of hepatitis C with Harvoni® results in a high SVR(>10) without regard to race, HIV co-infection, previous treatment status or whether the patient is treated in a gastroenterology or infectious disease clinic setting.


No benefits in any form have been received or will be received from a commercial party related to the subject of this article. All authors have read and approved the final manuscript.


1. Ward JW. The hidden epidemic of hepatitis C virus infection in the United States: occult transmission and burden of disease. Top Antivir Med. 2013; 21(1): 15-19. [PMID: 23596274]

2. Maasoumy B, Wedemeyer H. Natural history of acute and chronic hepatitis C. Best Pract Res Clin Gastroenterol. 2012; 26(4): 401-412. [PMID: 23199500]; [DOI: 10.1016/j.bpg.2012.09.009

3. Kanwal F, Hoang T, Kramer JR,Asch SM, Goetz MB, Zeringue A, Richardson P, El-Serag HB. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology. 2011; 140(4): 1182-1188.e1. [PMID: 21184757]; [DOI: 10.1053/j.gastro.2010.12.032]

4. El Serag HB, Mason A. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999; 340: 745-750. [PMID: 10072408]; [DOI: 10.1056/NEJM199903113401001]

5. Mir HM, Stepanova M, Afendy M, Kugelmas M, Younossi ZM. African Americans are less likely to have clearance of hepatitis C virus infection: the findings from recent U.S. population data. J Clin Gastroenterol. 2012; 46: e62-e65. [PMID: 22178959]; [DOI: 10.1097/MCG.0b013e318238352b]

6. Howell C, Jeffers L, Hoofnagle JH. Hepatitis C in African Americans: summary of a workshop. Gastroenterology. 2000; 119: 1385-1396. [PMID: 11054398]; [DOI: 10.1053/gast.2000.19582

7. Pyrsopoulos N, Jeffers L. Hepatitis C in African Americans. J Clin Gastroenterol. 2007; 41: 185-193. [PIMID: 27740516]; [DOI: 10.1016/j.cgh.2013.06.006

8. Wilder J, Saraswathula S, Saddelblad V, Muir A. A systematic review of race and ethnicity in Hepatitis C clinical trial enrollment. J Nat Med Assoc. 2016; 108: 24-29. [PMID: 26928485]; [DOI: 10.1016/j.jnma.2015.12.004

9. Rutledge, B., Vipul Mahajan, Paul Naylor, Sindhuri Benjaram, Murray Ehrinpreis, Milton Mutchnick Similarities in Hepatitis C Patient Profiles Over a Decade in an Urban GI Clinic. Journal of Gastroenterology and Hepatology Research 2017 December 21; 6(6): 2470-247. [DOI: 10.17554/j.issn.2224-3992.2017.06.739]

10. Stubbs A, Naylor P, Ravindran K, Benjaram S, Reddy N, Mutchnick S, May E, Ehrinpreis M, Mutchnick M. Racial diversity in mortality and morbidity in urban patients with hepatitis C. J Viral Hepat. 2016 Jun; 23(6): 439-46. Epub 2016 Jan 28 [PMID: 26818494]; [DOI: 10.1111/jvh.12504]

11. Kinzie JL, Naylor PH, Nathani MG, Peleman RR, Ehrinpreis MN, Lybik M, Turner JR, Janisse JJ, Massanari M, Mutchnick MG. African Americans with genotype 1 treated with interferon for chronic hepatitis C have a lower end of treatment response than Caucasians. J Viral Hepat. 2001 Jul; 8(4): 264-9. [PMID: 11454177]; [DOI: 10.1046/j.1365-2893.2001.00292.x]

12. Reddy N, Naylor P, Hakim Z, Asbahi R, Ravindran K, May E, Ehrinpreis M, Mutchnick M. Effect of Treatment for CHC on Liver Disease Progression and Hepatocellular Carcinoma Development in African Americans. J Clin Transl Hepatol. 2015 Sep 28; 3(3): 163-8. Epub 2015 Sep 15. [PMID: 26623262]; [DOI: 10.14218/JCTH.2015.00013]

13. Jeffers LJ. Treating hepatitis C in African Americans. Liver Int. 2007; 27: 313-322. [PMID: 17355451]; [DOI: 10.1111/j.1478-3231.2006.01438.x]

14. Karoney MJ, Siika AM. Hepatitis C virus (HCV) infection in Africa: a review. Pan Afr Med J. 2013; 14: 44. [PMID: 238560127]; [DOI: 10.11604/pamj.2013.14.44.2199]

15. Flamm SL, Muir AJ, Fried MW, et al. Sustained virologic response rates with telaprevir-based therapy in treatment-naive patients evaluated by race or ethnicity. J Clin Gastroenterol. 2015; 49(4): 336-344. [PMID: 24828357]; [DOI : 10.1097/MCG.0000000000000150]

16. Naylor P, Alebouyeh N, Mutchnick S Bastien M, Ehrinpreis M, May E, Muitchnick M. Interferon (IFN) based treatment of African Americans with Chronic Hepatitis C (CHC) in an Urban Clinic: improving response with advances in therapy. J Gastroenterol Hepatol Res. 2015; 4(2): 1465-1469. [DOI: 10.6051/j.issn.2224-3992.2015.04.482]

17. Falade-Nwulia O, Catalina Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB Sulkowski MS. Oral Direct-Acting Agent therapy for Hepatitis C virus infection: A systemic Review. Ann Intern Med. 2017; 166(9): 637-648. [PMID: 28319996]; [DOI: 10.7326/M16-2575]

18. Toussaint-Miller KA, Andres J. Treatment considerations for unique patient populations with HCV Genotype 1 infection. Ann Pharmacother. 2015; 49(9): 1015-1030. [PMID: 26139639]; [DOI: 10.1177/1060028015592015]

19. Wilder JM, Jeffers LJ, Ravendhran N, Shiffman ML, Poulos J, Sulkowski MS, Gitlin N, Workowski K, Zhu Y, Yang JC, Pang PS, McHutchison JG, Muir J, Howell C, Kowdley K, Afdhal N, Reddy KR. Safety and efficacy of ledipasvir-sofosbuvir in black patients with hepatitis C virus infection: a retrospective analysis of phase 3 data. Hepatology. 2016; 63(2): 437-444.[PMID: 26547499]; [DOI: 10.1002/hep.28334]

20. Naylor PH, Mutchnick M. Decreasing racial disparity with the combination of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C. Hepat Med. 2017 Mar 16; 9: 13-16.[PMID: 28356778]; [DOI: 10.2147/HMER.S118063]

21. Naylor P, Sahni N, Benjaram S, Ehrinpreis M, and Mutchnick, M. African American Patients Derive Significant Benefit from the Dual DAA Therapy: A Real World Study in an Urban Medical Center, Remedy /Access 2017 2: 1054

22. Backus LI, Belperio PS, Shahoumian TA, Loomis TP, Mole LA. Effectiveness of sofosbuvir-based regimens in genotype 1 and 2 hepatitis C virus infection in 4026 U.S. Veterans. Aliment Pharmacol Ther. 2015; 42(5): 559-573. [PMID: 26113432]; [DOI: 10.1111/apt.13300]

23. Su F, Green PK, Berry K, Ioannou GN. The association between race/ ethnicity and the effectiveness of direct antiviral agents for hepatitis C virus infection. Heptology. 2017; 65(2): 426-438. [PMID: 27775854]; [DOI: 10.1002/hep.28901]

24. Fox DS, McGinnis JJ, Tonnu-Mihara I, McCombs JS. Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: data from the Veterans Administration. J Gastroenterol Hepatol. Epub 2016 Nov 21. [PMID: 27869323]; [DOI: 10.1111/jgh.13652]


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