NS5A/ NS3 Combo Hepatitis C Treatment Delivers Excellent Sustained Virologic Response in Patients Coinfected with HIV

A drug combination of daclatasvir and asunaprevir plus interferon/ribavirin had high success rates in a 24-week clinical trial for treatment of hepatitis C in patients who also have HIV, according to study results released at the annual Conference on Retroviruses and Opportunistic Infections in Seattle.

While new oral drugs have made major advancements in treatment of hepatitis C among patients coinfected with HIV, more data is needed especially for patients with genotype 4 hepatitis C and cirrhotic patients, said Lionel Piroth, MD, PhD, of Centre Hospitalier Universitair de Dijon in Dijon France, who presented final results from the trial.

Daclatasvir is an NS5A replication complex inhibitor and asunaprevir is an NS3 protease inhibitor that when combined with pegylated interferon-ribavirin have shown promising results for mono-infected patients, the authors note in the study abstract.

The trial was an open-label, single-arm phase 2 study that evaluated the combined drugs in coinfected patients with genotypes 1 or 4 hepatitis C, who were null responders to prior pegylated interferon-ribavirin standard therapy. To be eligible patients had to have measurable HIV RNA levels.

The study involved 59 men and 16 women with an average age of 50. Of those patients, 27 had cirrhosis of the liver. All patients were on a raltegravir-based regimen and 92% had baseline level 3 plasma HIV viral load. Plasma hepatitis C viral load was 6.1 (5.8 - 6.6) log10 UI/mL, according to the abstract.

Results of the study showed that the global sustained virologic response (SVR) rate at 12 weeks following treatment was 96%. Among subgroups of the study population, the SVR12 rate was 92.6% in cirrhotic patients, 94.6% in genotype 1 patients and 97.4% in genotype 4 patients.

The hepatitis C virus was undetectable in 11 patients (15%) at study week 5, in 28 patients (38%) at week 6 and in 45 patients (60%) at week 8, according to the abstract. In the 51 patients experiencing less than a 1 log10 IU/ml HCV RNA decrease during the lead-in phase, SVR12 was 94.1%.

Out of 6 patients who prematurely stopped taking the study drug regimen, two stopped due to virologic breakthrough and four stopped because of adverse events that included lung cancer and three infections, according to the abstract.

The study authors concluded that a very high SVR12 rate was associated with a 24-week regimen that combined daclatasvir, asunaprevir, and pegylated interferon-ribavirin in patients coinfected with HIV and genotype 1 or 4 hepatitis C virus who were null responders, and of whom one-third had cirrhosis.

“The safety profile was acceptable, even though cirrhotic patients with low albumin and platelet levels should be closely monitored,” said the authors. “This combination represents a new treatment option in this highly difficult to treat population.”