January 30, 2018
2 min read

Immunosuppression, cirrhosis decrease SVR rates in HIV/HCV coinfection

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Direct-acting antiviral therapy was safe and highly effective in patients coinfected with HIV and hepatitis C, according to study results from the Madrid Coinfection Registry, or Madrid-CoRe. Factors that negatively affected sustained virologic response rates included HIV-related immunosuppression, HCV RNA load, severity of liver disease and suboptimal DAA-based regimens.

Juan Berenguer, MD, PhD
Juan Berenguer

“This huge sample provided by Madrid-CoRe gave us the opportunity to assess treatment outcomes for various all-oral DAA regimens against several genotypes in different categories of liver disease and to evaluate predictors of treatment response, which are difficult to determine for such a highly successful therapy,” Juan Berenguer, MD, PhD, from the Hospital General Universitario Gregorio Marañón, Spain, told Healio Gastroenterology and Liver Disease. “It is also of note that, our multivariable model showed that the probability of failure was highest for decompensated cirrhosis, intermediate for compensated cirrhosis, and lowest for the absence of cirrhosis, with statistically significant pair-wise comparisons between the three groups.”

Berenguer and colleagues prospectively followed 2,396 patients with HIV/HCV-coinfection during treatment. Median patient age was 51 years, 78.2% were men, 63.9% were treatment-naive, 803 had compensated cirrhosis and 156 had decompensated cirrhosis. Patients had HCV genotype 1a (40.9%), 1b (15.1%), 3 (15%) or 4 (22.4%).

Overall SVR rates were 92% according to intention-to-treat (ITT) and 94.1% according to modified intention-to-treat, in which the researchers removed non-virological failures for reasons other than discontinuation of treatment secondary to adverse events or death.

SVR rates were above 90% for all patients without cirrhosis and those with compensated cirrhosis except for one group. Patients with compensated cirrhosis who received Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) with ribavirin for 24 weeks had an ITT SVR of 88.5%; however, the modified ITT SVR in this group was 90.2%.

SVR rates for those with decompensated cirrhosis ranged from 72.7% in patients with HCV genotype 3 up to 93.7% in patients with genotype 1b based on both ITT and modified ITT.

Multivariate analysis showed significantly increased odds for virologic failure among men (OR = 1.75; 95% CI, 1.14-2.69) and patients with Centers for Disease Control and Prevention clinical category C (OR = 1.65; 95% CI, 1.12-2.41), baseline CD4+ T-cell count less than 200 mm3 (OR = 2.3; 95% CI, 1.35-3.92), HCV RNA load of 800,000 IU/mL or higher (OR = 1.63; 95% CI, 1.14-2.36), compensated cirrhosis (OR = 1.35; 95% CI, 0.96-1.89) or decompensated cirrhosis (OR = 2.92; 95% CI, 1.76-4.87).

Additionally, patients who received Sovaldi (sofosbuvir, Gilead Sciences) with simeprevir (OR = 2.84; 95% CI, 1.53-5.29), Sovaldi with ribavirin (OR = 3.41; 95% CI, 1.39-8.36) or Daklinza (daclatasvir, Bristol-Myers Squibb) with simeprevir (OR = 11.77; 95% CI, 1.59-87.27) had increased odds for virologic failure.

“The high SVR rates of most currently licensed all oral DAA-based regimens against HCV and the relatively small number of patients included in registration trials have made it difficult to identify predictors of treatment failure,” the researchers wrote. “Nevertheless, genotype 3, cirrhosis, liver decompensation, and pre-existing resistance-associated variants all seem to reduce the probability of SVR.” – by Talitha Bennett

Disclosure: Berenguer reports he received research grants from AbbVie, Gilead Sciences and Merck; and personal fees from AbbVie, Gilead Sciences, Janssen and Merck. Please see the full study for the other authors’ relevant financial disclosures.