Almost all HIV / HCV co-infected patients, treated for 12 weeks with a sofosbuvir (Sovaldi) and daclatasvir (Daklinza) free interferon and ribavirin regimen achieved a sustained virological response, however, the cure rate dropped to 76 to those treated for just 8 weeks, according to the results of the ALLY-2 study presented at “Digestive Disease Week 2015” last month in Washington, DC.
The development of direct action oral antiviral agents (AADs) that target different stages of the hepatitis C virus (HCV) life cycle has revolutionized treatment, offering a therapy that is shorter, better tolerated and more effective than therapy based on interferon. Unlike interferon, DAAs seem to work just as well in HIV-positive people with hepatitis C, who tend to experience faster progression of liver disease, than those with HCV infection only.
Kenneth Sherman of the University of Cincinnati presented the conclusions of the ALLY-2 phase 3 study, which evaluated the Gilead Sciences polymerase nucleotide inhibitor, sofosbuvir plus daclatasvir, from Bristol-Myers Squibbs NS5A without ribavirin.
Daclatasvir is pangenotipico - meaning it works against several HCV genotypes - unlike ledipasvir, the NS5A inhibitor in Gileads Harvonicoformulation.
The ALLY-2 study had 203 enrolled patients with chronic hepatitis C, 151 of whom had not been previously treated and 52 had not responded adequately to previous therapy (s).
Almost 90 were men, about 60 were white, about 35 were black and the average age was approximately 55 years. Most (83) had HCV genotype 1, with a majority of these having the 1st subtype, which is more difficult to treat, while 9 had genotype 2, six had genotype 3 (now considered more difficult to treat) and two, the type 4 genotypes. Just below 10% of the patients were “treatment virgins” and 29 patients had been previously treated and had liver cirrhosis.
Participants were also antiretroviral therapy (ART), with an undetectable HIV viral load or not yet on ART (Antiretroviral Therapy) with a T cell count, CD4, of at least 350 cells / mm3.
Almost all were on ART, with half taking HIV protease inhibitors, 25 taking INNTR and 25 taking other regimens, especially with integrase inhibitors; the median baseline of the CD4 count was cells / mm3 565.
All participants on the studied open label received 400mg sofosbuvir plus daclatasvir once daily. The standard dose of daclatasvir 60mg was adjusted to up to 30 mg when taken in combination with ritonavir protease inhibitors, or up to 90 mg when used with most INNTR to consider drug interactions.
Previously, untreated patients were randomized to 8 or 12 weeks of treatment, while all patients "experienced in treatment" were treated for 12 weeks.
Sherman reported that 96% of patients being treated with genotype 1 and 98% of patients previously treated for 12 weeks achieved a sustained or undetectable HCV RNA response for 12 weeks after completing treatment (SVR12). The sustained response rate dropped to just 76%, however, for genotype 1, in patients treated for just 8 weeks.
Response rates were similar when looking at all genotypes combined.
People with cirrhosis have somewhat lower cure rates than patients without cirrhosis in both arms of the study, being that of 8 weeks (60 vs 77) and 12 weeks arm (91 vs 99).
There was a relapse in both arms at 12 weeks and ten relapses in the study arm at eight weeks. Two relapsers at 12 weeks had HCV infection of subtype 1a, difficult to treat.
The treatment was, in general, safe and well tolerated, with no serious adverse events or adverse events that would lead to treatment interruption. Most of the participants kept their HIV viral load and CD4 counts stable (only one of them was lost during follow-up [translator's note: usually means that the patient (s) in question left / did not attend) to the research routine] and a seropositive patient had a “rebound” (resurgence of pathological agent) after completing treatment for hepatitis C.
Treatment of co-infected patients with HIV / HCV with daclatasvir sofosbuvir once a day for 12 weeks was well tolerated, the researchers concluded.
Daclatasvir Sofosbuvir was effective in patients with cirrhosis and in patients with other demographic data and a wide range of combinations of ART regimens without compromising HIV antibody control.
These findings have recently been updated by European professionals in hepatitis C treatment guidelines and current guidelines in the US, recommending that HIV-positive and HIV-negative people should be treated the same for hepatitis C, with exceptions, taking into account potential interactions with antiretroviral drugs.
Produced in collaboration with hivandhepatitis.com
Published: June 3 2015
Translated by Claudio Souza's original Sofosbuvir plus daclatasvir for 12 weeks cures most HIV / HCV coinfected
Wyles D et al (Sherman K presenting). Daclatasvir plus sofosbuvir for treatment of HCV genotypes 1-4 in HIV-HCV coinfection: the ALLY-2 studand. Digestive Disease Week, Washington, DC, abstract 901d, 2015.