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CROI 2015: Good Sofosbuvir/Ledipasvir Adherence in SYNERGY and ERADICATE Trials

Overall adherence rates ranged from 96% to nearly 100% in 2 clinical trials of sofosbuvir/ledipasvir (Harvoni) treatment in an urban population of hepatitis C and HIV/HCV coinfected patients traditionally considered difficult to treat, researchers reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Adherence dropped off over time, however, underlining the importance of short-duration therapy.

The advent of direct-acting antiviral agents that can be used in interferon-free regimens has made hepatitis C treatment more effective, convenient, and easier to tolerate. While many people do not complete interferon-based therapy due to its long treatment duration and difficult side effects, interferon-free treatment encourages higher adherence and better outcomes, including for people historically considered "difficult to treat" due to factors such as poverty, homelessness, or substance use.

Kerry Townsend from the National Institute of Allergy and Infectious Diseases (NIAID) and fellow investigators trials looked at adherence among previously untreated participants in the SYNERGY and ERADICATE trials who were treated with sofosbuvir/ledipasvir in a once-daily coformulation for 12 weeks.

Both studies, conducted by NIAID, enrolled primarily low-income people in the Washington, DC area. This analysis included 20 HCV monoinfected patients in SYNERGY (additional patients who also used a third direct-acting antiviral were excluded) and 50 HIV/HCV coinfected patients in ERADICATE.

Overall, about three-quarters were men, more than 80% were African-American, and the median age was approximately 59 years. More than 70% had harder-to-treat HCV subtype 1a and nearly one-third had advanced liver fibrosis or cirrhosis (Metavir stage F3-F4). In addition, about one-third had a history of psychiatric diagnosis, nearly half had consumed alcohol during the past month, 10%-30% had used marijauna or cocaine in the past 6 months, and nearly 40% were unemployed.

Among the ERADICATE participants, 37 were on antiretroviral therapy (ART) while 13 had not yet started HIV treatment. The researchers hypothesized that coinfected patients on ART with good HIV control might have better adherence to hepatitis C treatment than HCV monoinfected people or coinfected people not on ART. Adherence was assessed by 3 methods: Medication Event Monitoring System (MEMS) caps that record when a pill bottle is opened, pill counts, and participant self-reports.

Results

• Patients in all 3 treatment groups (HCV moninfected, coinfected on ART, and coinfected not on ART) experienced rapid HCV viral load decline consistent with good adherence.
• Adherence over 12 weeks was high according to all 3 measures, but somewhat lower according to MEMS caps (around 97%) compared to pill counts (98%-99%) and patients reports (99%-100%).
• Based on pill counts, 50% of participants missed no doses, 40% missed 1-4 doses, 3% missed 5-8 doses, and 7% missed more than 8 doses.
• These proportions did not differ significantly between HCV monoinfected and coinfected patients, or between coinfected people on or off ART.
• Adherence according to MEMS caps decreased from week 4 to week 12 in all groups.
• All but 1 patient (99%) achieved sustained virological response, or continued undetectable HCV RNA at 12 weeks post-treatment.
• The 1 relapser kept meds in a pill organizer box, which made it harder to assess adherence, but returned no unused pills.

"Adherence to the single daily tablet of ledipasvir/sofosbuvir was high in this urban population and did not significantly differ among HCV monoinfected, HIV/HCV coinfected [ART] treated, and HIV/HCV coinfected [ART] untreated patients," the researchers concluded. "Adherence did significantly decline over time in all 3 groups, suggesting pill fatigue, and needs to be evaluated in larger patient population in real-life scenarios."

4/10/15

Reference

KS Townsed, TL Petersen, LA Gordon, S Kottilil, Et al. Effect of HIV Coinfection on Adherence to a 12-Week Regimen of HCV Therapy With Ledipasvir/Sofosbuvir. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 692.