Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients

Objectives Development of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients. Methods Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat’AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed. Results Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%), sofosbuvir/ledipasvir (0.2%/67.6%), daclatasvir (0%/49.4%), ombitasvir/boosted paritaprevir (with or without dasabuvir) (34.4%/52.2%) and simeprevir (78.8%/0%). Conclusions Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.

[1]  Christopher D Miller,et al.  A Cross-Sectional Study Comparing the Frequency of Drug Interactions After Adding Simeprevir- or Sofosbuvir-Containing Therapy to Medication Profiles of Hepatitis C Monoinfected Patients , 2015, Infectious Diseases and Therapy.

[2]  Rebecca J. Cope,et al.  Majority of HIV/HCV Patients Need to Switch Antiretroviral Therapy to Accommodate Direct Acting Antivirals. , 2015, AIDS patient care and STDs.

[3]  S. Pol,et al.  Treatment of acute hepatitis C in human immunodeficiency virus–infected patients: The HEPAIG study , 2010, Hepatology.

[4]  G. Ioannou,et al.  Prevalence and treatment of chronic hepatitis C virus infection in the US Department of Veterans Affairs. , 2015, Epidemiologic reviews.

[5]  T. Asselah,et al.  Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial , 2015, The Lancet.

[6]  Stefan Zeuzem,et al.  Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. , 2014, The New England journal of medicine.

[7]  T. Heeren,et al.  Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  S. Khoo,et al.  Drug interactions between antiretrovirals and new or emerging direct-acting antivirals in HIV/hepatitis C virus coinfection , 2014, Current opinion in infectious diseases.

[9]  Christopher D Miller,et al.  Prevalence of drug-drug interactions upon addition of simeprevir- or sofosbuvir-containing treatment to medication profiles of patients with HIV and hepatitis C coinfection. , 2015, AIDS research and human retroviruses.

[10]  Martin Fisher,et al.  Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men. , 2009, Gastroenterology.

[11]  C. Stedman,et al.  Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. , 2013, The New England journal of medicine.

[12]  K. Sherman,et al.  HIV/hepatitis C coinfection natural history and disease progression. , 2011, Current opinion in HIV and AIDS.

[13]  L. Cuzin,et al.  A large French prospective cohort of HIV‐infected patients: the Nadis Cohort , 2009, HIV medicine.

[14]  R. Weber,et al.  High hepatic and extrahepatic mortality and low treatment uptake in HCV-coinfected persons in the Swiss HIV cohort study between 2001 and 2013. , 2015, Journal of hepatology.

[15]  Brad J. Wood,et al.  Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. , 2015, JAMA.

[16]  J. Rockstroh,et al.  Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study , 2015, The Lancet.

[17]  Aasld Idsa Hcv Guidance Panel Hepatitis C guidance: AASLD‐IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus , 2015, Hepatology.

[18]  F. Torriani,et al.  The Hepatitis C Cascade of Care among HIV Infected Patients: A Call to Address Ongoing Barriers to Care , 2014, PloS one.

[19]  Soriano,et al.  Temporal changes and regional differences in treatment uptake of hepatitis C therapy in EuroSIDA , 2012 .

[20]  J. Pawlotsky,et al.  EASL Recommendations on Treatment of Hepatitis C 2015. , 2015, Journal of hepatology.

[21]  A. Lok,et al.  Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. , 2014, The New England journal of medicine.

[22]  B. Conway,et al.  Who Needs Direct-Acting Antivirals for HCV? Challenges Faced in Advancing HCV Therapy for HIV–HCV-Coinfected Individuals , 2013, Antiviral therapy.

[23]  V. Soriano,et al.  Combination Therapy With Telaprevir for Chronic Hepatitis C Virus Genotype 1 Infection in Patients With HIV , 2013, Annals of Internal Medicine.

[24]  T. Pilot‐Matias,et al.  Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. , 2015, JAMA.

[25]  N. Huo,et al.  New progress on the treatment of hepatitis C: the interpretation of EASL Recommendations on Treatment of Hepatitis C 2015 , 2015 .

[26]  E. Operskalski,et al.  HIV/HCV Co-infection: Pathogenesis, Clinical Complications, Treatment, and New Therapeutic Technologies , 2011, Current HIV/AIDS reports.

[27]  V. Soriano,et al.  Drug interactions with new hepatitis C oral drugs , 2015, Expert opinion on drug metabolism & toxicology.

[28]  J. Mallolas,et al.  Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial. , 2013, The Lancet. Infectious diseases.

[29]  Qilong Yi,et al.  Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis , 2008, AIDS.

[30]  D. Neau,et al.  Telaprevir for HIV/hepatitis C virus-coinfected patients failing treatment with pegylated interferon/ribavirin (ANRS HC26 TelapreVIH): an open-label, single-arm, phase 2 trial. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  F. Dabis,et al.  Burden of HIV and hepatitis C co‐infection: the changing epidemiology of hepatitis C in HIV‐infected patients in France , 2015, Liver international : official journal of the International Association for the Study of the Liver.

[32]  Brian L. Pearlman,et al.  Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study , 2014, The Lancet.

[33]  C. Umscheid,et al.  The Treatment Cascade for Chronic Hepatitis C Virus Infection in the United States: A Systematic Review and Meta-Analysis , 2014, PloS one.