Naggie presents PHOTON-1 results at CROI 2014

March 7, 2014 – A 24-week interferon-free regimen of sofosbuvir plus ribavirin showed promise for patients with genotype-1 hepatitis C and HIV.

A 24-week interferon-free regimen of sofosbuvir plus ribavirin showed promise for patients with genotype-1 hepatitis C and HIV, but a shorter regimen did not seem to be as effective for patients with genotype-3 hepatitis C, according to a report presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI) this week in Boston.

The results are the latest from the PHOTON-1 trial, an open-label phase 3 study of sofosbuvir plus ribavirin for co-infected individuals with hepatitis C virus (HCV) genotypes 1, 2 or 3. Susanna Naggie, MD, director of the Infectious Disease division of the DCRI, presented the findings at CROI.

susanna-naggie-newsPeople with HIV/HCV co-infection experience more rapid liver disease progression and do not respond as well to interferon-based therapy as people with hepatitis C alone. Direct-acting antivirals that target different steps of the HCV lifecycle offer the prospect of shorter treatment, fewer side-effects and higher cure rates for both HCV mono-infected and HIV/HCV co-infected patients.

PHOTON-1 enrolled 114 people with genotype 1 HCV and HIV co-infection who had not previously taken treatment for hepatitis C. They received once-daily sofosbuvir plus weight-based ribavirin for 24 weeks. The study also included 68 treatment-naive and 41 treatment-experienced people with HCV genotypes 2 or 3. Previously untreated patients received sofosbuvir and ribavirin for 12 weeks while prior non-responders were treated for 24 weeks.

Across all study arms, most participants (about 85 percent) were men and the mean age was about 50 years. One-third of participants with HCV genotype 1 and about 15 percent of participants with genotype 2 or 3 were black. Thirty percent of treatment-naive patients and half of treatment-experienced participants had the favorable IL28B CC gene variant associated with good interferon responsiveness. Most genotype 1 patients (79 percent) had harder-to-treat subtype 1a. Rates of liver cirrhosis ranged from 4 percent among treatment-naive genotype 1 patients to 24 percent in the treatment-experienced genotype 2/3 group.

Naggie reported final data from the study, including sustained virological response rates, or continued undetectable HCV RNA, at weeks 12 and 24 post-treatment (SVR12 and SVR24). Looking at the treatment-naive genotype 1 patients, 76 percent achieved SVR12. One person had detectable HCV again after completing treatment – giving an SVR24 rate of 75 percent – but this may have been a case of re-infection rather than relapse. Among treatment-naive genotype 2 patients treated for 12 weeks, the SVR12 and SVR24 rates were both 88 percent. Among treatment-naive genotype 3 patients treated for the same duration, however, the SVR12 and SVR24 rates fell to 67 percent. Among treatment-experienced people treated for 24 weeks, SVR24 rates were 92 percent for genotype 2 and 94 percent for genotype 3.

Sofosbuvir plus ribavirin was generally safe and well tolerated. Seven people treated for 12 weeks and six treated for 24 weeks experienced serious adverse events, and four and three patients, respectively, discontinued treatment for this reason. The most common side effects were fatigue, insomnia, headache and nausea.

In her presentation, Naggie said the use of direct-acting antivirals appears to overcome the disadvantage in treatment response for people with HIV that was seen with interferon.

“I believe HIV is no longer a player,” she said.