Sofosbuvir/Daclatasvir Cures Advanced HCV in 100% of HIV Group

Sofosbuvir (Sovaldi) plus daclatasvir (Daklinza), two anti-HCV (hepatitis C) direct-acting antivirals (DAAs), yielded sustained virologic response 12 weeks after treatment ended (SVR12) in a study of 31 patients with advanced liver disease and HIV coinfection. Significantly improved liver stiffness suggested that the DAAs had antifibrotic effects, according to the study.

Approximately one-quarter of people with HIV infection are coinfected with the hepatitis C virus. When standard therapy for HCV infection consisted of interferon plus ribavirin, HIV was a risk factor for treatment failure. Trials of diverse DAAs indicate that these agents cure HCV in HIV-coinfected patients as readily as in HIV-negative people. But clinical trials often exclude patients with more advanced liver disease.

Researchers in Vienna conducted this retrospective study of two DAAs, sofosbuvir plus daclatasvir, in HCV/HIV-coinfected patients with advanced liver disease to gauge the antiviral impact and safety of a standard DAA regimen in a real-world population. They focused on sofosbuvir/daclatasvir because its activity against multiple HCV genotypes and favorable drug-drug interaction profile make it appropriate for nearly all patients with HCV/HIV coinfection.

The study involved 31 HCV/HIV-coinfected patients with advanced liver disease treated with sofosbuvir/daclatasvir at the Medical University of Vienna. The researchers collected relevant epidemiologic and disease data from medical records. They assessed liver stiffness with transient elastography, a noninvasive marker of liver fibrosis that predicts hepatic decompensation and hepatocellular carcinoma.

DAA therapy lasted 12 weeks for patients with HCV genotype 1 or 4 without cirrhosis, 24 weeks for genotype 1 or 4 with cirrhosis and 24 weeks for genotype 3. If HCV RNA could be detected four weeks before the scheduled end of treatment, therapy continued for an additional four weeks. The daclatasvir dose was 30 mg daily in patients taking a ritonavir-boosted protease inhibitor, 90 mg daily in those taking a nonnucleoside and 60 mg daily in a patient taking both a protease inhibitor and a nonnucleoside. All patients took 400 mg of sofosbuvir once daily.

Twenty patients (65%) were men, and age averaged 49.2 years. Only one patient was not taking antiretroviral therapy, and 25 had HIV RNA below 50 copies/mL. Sixteen patients had anti-HCV treatment experience, 21 were infected with HCV genotype 1, seven with genotype 3, and three with genotype 4. All but two patients had liver stiffness greater than 9.5 kPa or METAVIR fibrosis stage higher than F2, while 14 patients had liver stiffness greater than 12.5 kPa or METAVIR stage F4. Seven of 27 patients with information on portal hypertension (26%) had clinically significant portal hypertension. Sixteen of 31 patients (52%) had cirrhosis.

HCV RNA could not be detected in any patient at the end of treatment. All patients achieved SVR4 and SVR12. Four patients (13%) had grade 3 or 4 adverse events, and two (6%) had serious adverse events. No grade 3 or 4 or serious adverse events were considered related to treatment, and no one stopped treatment because of adverse events.

An average 32.7 weeks passed between the start of DAA therapy and liver stiffness measurement. Liver stiffness decreased in 28 of 31 patients (90%) and increased in three. Median liver stiffness declined 3.6 kPa (P < .001). Median liver enzyme levels also decreased significantly after DAA therapy: -16 U/L for aspartate aminotransferase, -22 U/L for alanine aminotransferase and -54 U/L for gamma-glutamyltransferase (P < .001 for all changes).

The researchers stress that a 33% median relative decline in liver stiffness during follow-up indicates "a rapid, clinically significant effect." Decreased liver stiffness, they suggest, "might abolish the need for [hepatocellular carcinoma] surveillance and screening endoscopies."