AASLD 2016: Sofosbuvir/ Ledipasvir Effective for HIV/HCV Coinfected People in Real-World Cohorts


The sofosbuvir/ledipasvir (Harvoni) coformulation used in real-world clinical practice produced good sustained virological response rates similar to those seen in clinical trials for HIV-positive people coinfected with hepatitis C, according to a pooled analysis presented at the 2016 AASLD Liver Meeting this month in Boston.

HIV-positive people coinfected with hepatitis C virus (HCV) experience more rapid liver disease progression on average and did not respond as well as HIV-negative people to interferon-based hepatitis C treatment. Clinical trials have shown that the new direct-acting antiviral agents used in interferon-free regimens work as well for HIV-positive as for HIV-negative people with hepatitis C -- so much so that coinfected patients are no longer considered a "special population." But outcomes in real-life clinical practice do not always match those of formal treatment trials in which participants are carefully selected and may receive more intensive monitoring and support.

Susanna Naggie from Duke University and colleagues compared the efficacy of the sofosbuvir/ledipasvir single tablet regimen for HIV/HCV coinfected people with HCV genotype 1 in clinical trials against its effectiveness in real-world cohorts.

This analysis looked at results data from 3 clinical trials of sofosbuvir/ledipasvir for coinfected patients:

  • Gilead Sciences' ION-4 trial(n=327)
  • The National Institute of Health ERADICATE trial (n=50)
  • The French ANRS HC31 SOFTRIH trial (n=68)

The comparison also included data from 4 real-world cohorts with at least 50 coinfected participants:

  • The TRIO cohort (n=150)
  • The Institute of Human Virology's ASCEND cohort (n=142)
  • A cohort from Portugal (n=166)
  • A U.S. Veterans Affairs (VA) cohort (n=270)

The cohorts represented diverse patient populations in the U.S. and Europe treated at academic medical centers, urban primary care clinics, and Veterans Health Administration facilities.

Across all trials and cohorts the majority of patients (69%-97%) were men, most (60% to 100%) were non-cirrhotic, and the mean ages were 46 to 60 years. The proportion of treatment-experienced patients varied, but was similar for the trials as a whole and the cohorts as a whole. Participants had well-controlled HIV with a median CD4 cell count above 600 cells/mm3.

Clinical trial participants were treated with sofosbuvir/ledipasvir with or without ribavirin for 12 weeks, while real-world cohort participants received treatment for 8, 12, or 24 weeks.


  • In the clinical trials, rates of sustained virological response at 12 weeks post-treatment (SVR12) for genotype 1 coinfected patients were 96% in ION-4, 98% in ASCEND, and 100% in ANRS SOFTRIH.
  • SVR12 rates in the real-world cohorts were 97% (24 weeks) to 100% (8 weeks) in TRIO, 91% in ASCEND, 98% (12 weeks) to 99% (24 weeks) in the Portugal cohort, and 91% in the VA cohort.
  • In a pooled analysis, the overall SVR12 rates were 97% for participants in the clinical trials and 94% for patients in the real-world cohorts.
  • Cure rates were 93% and 92%, respectively, for black patients, 98% and 97% for treatment-experienced patients, and 96% and 94% for people with cirrhosis.

These findings show that HIV/HCV coinfected patients with HCV genotype 1 can do as well in real-world clinical practice as they did in clinical trials.

"SVR rates were high across all populations including populations with traditional negative predictors such as black race, cirrhosis, and treatment-experienced patients," the researchers concluded. "This descriptive analysis demonstrated that SVR rates from real-world cohorts are generalizable from clinical trials."

The results support the latest AASLD/IDSA guidelines and EASL guidelines,  which recommend sofosbuvir/ledipasvir for HIV/HCV coinfected patients, they added.



S Naggie, E Rosenthal, S Kattakuzhy, et al. Real World Effectiveness of Ledipasvir/Sofosbuvir (LDV/SOF) in Patients Coinfected With HCV and HIV-1: A Comparative Analysis of Clinical Trials with Four Real World Cohorts. AASLD Liver Meeting. Boston, November 11-15, 2016. Abstract 892.