Pharmacologic management of HCV treatment in patients with HCV monoinfection vs. HIV/HCV coinfection: Does coinfection really matter?

Autoři: Autumn D. Zuckerman aff001;  Andrew Douglas aff002;  Kristen Whelchel aff001;  Leena Choi aff003;  Joshua DeClercq aff003;  Cody A. Chastain aff004
Působiště autorů: Specialty Pharmacy Services, Vanderbilt University Medical Center,; Nashville, Tennessee, United States of America aff001;  Christy Houston Foundation Drug Information Center, Belmont University College of Pharmacy; Nashville, Tennessee, United States of America aff002;  Department of Biostatistics, Vanderbilt University Medical Center,; Nashville, Tennessee, United States of America aff003;  Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center,; Nashville, Tennessee, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225434



Sustained virologic response (SVR) rates in patients with hepatitis C virus (HCV) monoinfection and human immunodeficiency virus (HIV)/HCV coinfection treated with direct acting antiviral (DAA) therapy are similar in clinical trials. The objective of this study was to examine differences in patient characteristics, drug-drug interactions, and treatment pathways between these groups in a real-world clinical setting.


We performed an ambispective review of patients prescribed DAA therapy between September 2015 and April 2018 at a tertiary academic center. The primary endpoint was time from a decision to treat to treatment initiation. Secondary endpoints included patient characteristics; frequency and type of DAA medication interactions; frequency, type, and timing of antiretroviral therapy (ART) changes; and treatment outcomes.


Three hundred and twelve patients were included. Almost half (43%) were HIV/HCV coinfected. Patients with HIV/HCV coinfection were more likely to be African American (p<0.001), have a diagnosed psychiatric disorder (p<0.001) and have a higher pill burden (p = 0.014). Patients with HIV/HCV coinfection were more likely to report an alcohol abuse history (p<0.001), injection drug use history (p<0.024), or active use of illicit substances (p = 0.019). In a multivariable regression model assessing the primary endpoint, time to treatment initiation was increased in patients requiring a change in ART therapy (OR = 9.2, p < 0.001) or a non-ART medication adjustment (OR = 2.4, p = 0.003), and in patients with Medicaid (OR = 6.7, p < 0.001). After controlling for all these factors, HIV/HCV coinfection still significantly impacted time to treatment initiation (OR = 1.7, p = 0.020). The groups had similar rates of drug interaction frequency, treatment completion, observed SVR, and side effects.


Patients with HIV/HCV coinfection are more likely to have a variety of factors that add complexities to HCV treatment. In addition to these challenges, patients with HIV/HCV coinfection experience a longer time to treatment initiation while patients with HCV monoinfection were more frequently lost to care. Care delivery models may incorporate this data to improve patient engagement, access, and outcomes.

Klíčová slova:

Co-infections – Drug therapy – Hepatitis C virus – Insurance – Pharmacists


1. Hofmeister MG, Rosenthal EM, Barker LK, Rosenberg ES, Barranco MA, Hall EW, et al. Estimating Prevalence of Hepatitis C Virus Infection in the United States, 2013–2016. Hepatology. 2019;69(3):1020–31. Epub 2018/11/07. doi: 10.1002/hep.30297 30398671.

2. Edlin BR. Access to treatment for hepatitis C virus infection: time to put patients first. The Lancet Infectious Diseases. 2016;16(9):e196–e201. doi: 10.1016/S1473-3099(16)30005-6 27421993

3. Raymond HF, Hughes A, O'Keefe K, Stall RD, McFarland W. Hepatitis C prevalence among HIV-positive MSM in San Francisco: 2004 and 2008. Sex Transm Dis. 2011;38(3):219–20. doi: 10.1097/OLQ.0b013e3181f68ed4 20938373.

4. Sherman KE, Rouster SD, Chung RT, Rajicic N. Hepatitis C Virus prevalence among patients infected with Human Immunodeficiency Virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis. 2002;34(6):831–7. doi: 10.1086/339042 11833007.

5. Frederick T, Burian P, Terrault N, Cohen M, Augenbraun M, Young M, et al. Factors associated with prevalent hepatitis C infection among HIV-infected women with no reported history of injection drug use: the Women's Interagency HIV Study (WIHS). AIDS Patient Care STDS. 2009;23(11):915–23. doi: 10.1089/apc.2009.0111 19877800; PubMed Central PMCID: PMC2823487.

6. Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014;384(9939):241–8. doi: 10.1016/S0140-6736(14)60604-8 25042234.

7. Farahani M, Mulinder H, Farahani A, Marlink R. Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis. Int J STD AIDS. 2016. doi: 10.1177/0956462416632428 26868158.

8. Trickey A, May MT, Vehreschild J, Obel N, Gill MJ, Crane H, et al. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy. PLoS One. 2016;11(8):e0160460. doi: 10.1371/journal.pone.0160460 27525413; PubMed Central PMCID: PMC4985160.

9. Portocarrero Nunez JA, Gonzalez-Garcia J, Berenguer J, Gallego MJV, Loyarte JAI, Metola L, et al. Impact of co-infection by hepatitis C virus on immunological and virological response to antiretroviral therapy in HIV-positive patients. Medicine (Baltimore). 2018;97(38):e12238. Epub 2018/09/22. doi: 10.1097/md.0000000000012238 30235668; PubMed Central PMCID: PMC6160110.

10. Bagwell AC, Cody. Hepatitis C Treatment in HIV Coinfection: Approaches, Challenges, and Future Opportunities. Current Treatment Options in Infectious Diseases. 2016. Epub October 7, 2016. doi: 10.1007/s40506-016-0097-1

11. Sikavi C, Najarian L, Saab S. Similar Sustained Virologic Response in Real-World and Clinical Trial Studies of Hepatitis C/Human Immunodeficiency Virus Coinfection. Dig Dis Sci. 2018;63(11):2829–39. Epub 2018/08/11. doi: 10.1007/s10620-018-5215-0 30094623.

12. Olea A, Grochowski J, Luetkemeyer AF, Robb V, Saberi P. Role of a clinical pharmacist as part of a multidisciplinary care team in the treatment of HCV in patients living with HIV/HCV coinfection. Integrated pharmacy research & practice. 2018;7:105–11. doi: 10.2147/IPRP.S169282 PMC6118274. 30214893

13. Rice DP, Ordoveza MA, Palmer AM, Wu GY, Chirch LM. Timing of treatment initiation of direct-acting antivirals for HIV/HCV coinfected and HCV monoinfected patients. AIDS Care. 2018;30(12):1507–11. Epub 2018/07/20. doi: 10.1080/09540121.2018.1499857 30021452.

14. Palaniswami PM, El Sayed A, Asriel B, Carollo JR, Fierer DS. Ledipasvir and Sofosbuvir in the Treatment of Early Hepatitis C Virus Infection in HIV-Infected Men. Open Forum Infect Dis. 2018;5(10):ofy238. Epub 2018/10/24. doi: 10.1093/ofid/ofy238 30349848; PubMed Central PMCID: PMC6189631.

15. Zuckerman A, Douglas A, Nwosu S, Choi L, Chastain C. Increasing success and evolving barriers in the hepatitis C cascade of care during the direct acting antiviral era. PLOS ONE. 2018;13(6):e0199174. doi: 10.1371/journal.pone.0199174 29912944

16. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research Electronic Data Capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. Journal of biomedical informatics. 2009;42(2):377–81. doi: 10.1016/j.jbi.2008.08.010 PMC2700030. 18929686

17. Harrell F. Regression Modeling Strategies. Verlag New York: Springer; 2001. XXIV, 572 p.

18. Lo Re V, Gowda C 3rd, Urick PN, Halladay JT, Binkley A, Carbonari DM, et al. Disparities in Absolute Denial of Modern Hepatitis C Therapy by Type of Insurance. Clin Gastroenterol Hepatol. 2016;14(7):1035–43. doi: 10.1016/j.cgh.2016.03.040 27062903; PubMed Central PMCID: PMC4912853.

19. Barua S, Greenwald R, Grebely J, Dore GJ, Swan T, Taylor LE. Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States. Ann Intern Med. 2015;163(3):215–23. doi: 10.7326/M15-0406 26120969.

20. Millman AJ, Ntiri-Reid B, Irvin R, Kaufmann MH, Aronsohn A, Duchin JS, et al. Barriers to Treatment Access for Chronic Hepatitis C Virus Infection: A Case Series. Top Antivir Med. 2017;25(3):110–3. 28820726.

21. Loy V, Benyashvili T, Adams W, Pavkov D, O'Mahoney M, Cotler SJ. The time and cost investment required to obtain and initiate direct-acting antiviral therapy. Antivir Ther. 2016;21(8):731–3. Epub 2016/07/14. doi: 10.3851/IMP3068 27414001.

22. Hepatitis C: the State of Medicaid Access: NVHR/Center for Health Law & Policy Innovation Harvard Law School; 2016. Available from:

23. Zuckerman A, Carver A, Chastain CA. Building a Hepatitis C Clinical Program: Strategies to Optimize Outcomes. Curr Treat Options Infect Dis. 2018;10(4):431–46. Epub 2018/12/14. doi: 10.1007/s40506-018-0177-5 30524209; PubMed Central PMCID: PMC6244618.

24. Bagwell A, Douglas A, Chastain C. Evaluation of the Hepatitis C Cascade of Care in a Multidisciplinary Infectious Diseases Clinic. Open Forum Infectious Diseases. 2017;4(suppl_1):S200–S. doi: 10.1093/ofid/ofx163.385

25. Langness JA, Nguyen M, Wieland A, Everson GT, Kiser JJ. Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions. World J Gastroenterol. 2017;23(9):1618–26. Epub 2017/03/23. doi: 10.3748/wjg.v23.i9.1618 28321163; PubMed Central PMCID: PMC5340814.

26. Messiera L, Verreaultc V, Arbourd P, Trudeauc C, Marcottec S, Sheehana N, et al., editors. Hi gh incidence of drug-drug interactions with hepatitis C direct-acting antivirals in patients hospitalized during their treatment (MONTREAL-C) 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis & Other Antiviral 2019; Noordwijk, the Netherlands.

27. Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889–98. Epub 2014/04/11. doi: 10.1056/NEJMoa1402454 24725239.

28. Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015;373(8):705–13. doi: 10.1056/NEJMoa1501315 26196665; PubMed Central PMCID: PMC4892372.

29. Kim HN, Nance RM, Williams-Nguyen JS, Chris Delaney JA, Crane HM, Cachay ER, et al. Effectiveness of Direct-Acting Antiviral Therapy in Patients With Human Immunodeficiency Virus-Hepatitis C Virus Coinfection in Routine Clinical Care: A Multicenter Study. Open forum infectious diseases. 2019;6(4):ofz100–ofz. doi: 10.1093/ofid/ofz100 30949539.

30. Backus LI, Belperio PS, Shahoumian TA, Mole LA. Direct-acting antiviral sustained virologic response: Impact on mortality in patients without advanced liver disease. Hepatology. 2018;68(3):827–38. Epub 2018/01/30. doi: 10.1002/hep.29811 29377196.

31. Younossi ZM, Stepanova M, Racila A, Afendy A, Lawitz EJ, Schwabe C, et al. Long-Term Benefits of Sustained Virologic Response for Patient-Reported Outcomes in Patients with Chronic HCV Infection. Clinical Gastroenterology and Hepatology. doi: 10.1016/j.cgh.2019.07.047 31376493

Článek vyšel v časopise


2019 Číslo 11