The sofosbuvir/ledipasvir (Harvoni) co-formulation used in real-world clinical practice produced good sustained virological response rates similar to those seen in clinical trials for HIV-positive people with hepatitis C co-infection, according to a pooled analysis presented at the 2016 AASLD Liver Meeting this month in Boston.
HIV-positive people who have co-infection 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 people with co-infection 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 of Duke University and colleagues compared the efficacy of the sofosbuvir/ledipasvir single tablet regimen for people with HIV/HCV co-infection with HCV genotype 1 in clinical trials against its effectiveness in real-world cohorts.
This analysis looked at results data from three clinical trials of sofosbuvir/ledipasvir for people with co-infection:
- 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 four real-world cohorts with at least 50 participants with co-infection:
- The TRIO cohort (n = 150)
- The Institute of Human Virology's ASCEND cohort (n = 142)
- A cohort from Portugal (n = 166)
- A US Veterans Affairs (VA) cohort (n = 270)
The cohorts represented diverse patient populations in the US and Europe treated at academic medical centres, urban primary care clinics and US Veterans Health Administration facilities.
Across all trials and cohorts the majority of patients (69-97%) were men, most (60-100%) did not have cirrhosis and the mean ages were 46 to 60 years. The proportion of treatment-experienced people 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 the rates of sustained virological response at 12 weeks post-treatment (SVR12) for people with genotype 1 who had co-infection were 96% in ION-4, 98% in ASCEND and 100% in ANRS SOFTRIH. SVR12 rates in the real-world cohorts were 98% in TRIO, 91% in ASCEND, 98% 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 people in the real-world cohorts. Cure rates were 93% and 92%, respectively, for black people, 98% and 97% for treatment-experienced people, and 96% and 94% for people with cirrhosis.
These findings show that people with HIV/HCV co-infection 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."
Naggie S 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. The 67th Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting, abstract 892, Boston, 2016.