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Liver cirrhosis a risk factor for treatment failure in HCV–HIV coinfection
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Liver cirrhosis is a risk factor for direct-acting antiviral therapy failure in patients coinfected with hepatitis C virus and HIV, according to researchers.
“This highlights the need for early initiation of [direct-acting antiviral (DAA)] therapy in HCV/HIV coinfected patients before the onset of higher liver fibrosis/cirrhosis to allow for optimal rates of viral eradication and to substantially reduce morbidity and mortality in this patient population,” Christoph Boesecke, MD, and infectious diseases specialist at Bonn University Hospital in Germany, and colleagues wrote in Open Forum Infectious Diseases.
The researchers included in their study 1,505 patients with HCV treated at nine facilities in Germany who received DAA therapy. Of those, 349 patients (23%) were coinfected with HIV and 1,156 (77%) had HCV monoinfection. In addition, 431 patients (29%) had liver cirrhosis. The median patient age was 52 years.
Of the patients who were coinfected, 61 (17%) had a baseline CD4 count of less than 350/µl. The median time of ART before DAA therapy was 6.4 years, with a range of 2.2 to 14.7 years.
The researchers assessed outcomes at 12 weeks after the end of DAA therapy to determine which patients had achieved SVR. Among the patients with coinfection and in univariate analysis, none of eight variables were significantly associated with SVR12. The variables were sex, age, HCV genotype, high HCV RNA, alanine aminotransferase count, prior HCV treatment, CD4 nadir and opiate substitution therapy.
Those with a CD4 count of less than 350/µl, CD4 less than 20% and liver cirrhosis were less likely to reach SVR12. However, the researchers said the low CD4 counts were probably due to splenomegaly, an enlargement of the spleen that can be caused by liver cirrhosis.
Therefore, liver cirrhosis alone was the only factor significantly associated with the risk of failure to achieve SVR12 (OR = 3.5; 95% CI, 1.20-9.90).
The researchers cautioned that the data should not discourage initiating DAA therapy.
“Our findings should by no means lead to DAA therapy being withheld from those at utmost need of HCV cure, HCV/HIV coinfected patients with advanced liver cirrhosis,” they wrote. “On the contrary, our findings should support and highlight the need for access to DAA therapy for all HCV-infected individuals and initiation of HCV treatment before the onset of advanced liver fibrosis, let alone cirrhosis, as currently recommended by HCV treatment guidelines.” – by Joe Green
Disclosure: Boesecke reports that he has received honoraria for consulting or educational lectures from AbbVie, Gilead Sciences, MSD and ViiV Healthcare. Please see the full study for all other authors’ relevant financial disclosures.
Perspective
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Interferon-free DAA-based therapy has revolutionized our approach to HCV treatment in both monoinfected individuals and those who are coinfected with HIV and HCV. Extremely high cure rates, as well as favorable safety and tolerability profiles, of all DAA regimens in both monoinfected and coinfected patients has led to guideline recommendations to treat all patients with HCV, regardless of HIV status.
Furthermore, because HIV is a known risk factor for rapid progression of fibrosis, people living with HIV and HCV are often prioritized to receive DAA-based therapy to avoid complications of cirrhosis.
In this study by Boesecke and colleagues, which analyzed 1,156 patients with HCV monoinfection and 349 patients with HIV/HCV coinfection, overall SVR rates were high in both groups (95%). However, low CD4 counts and the presence of cirrhosis were found as risk factors for impaired response in the coinfected population.
This study highlights two important points to consider when caring for patients with HIV/HCV coinfection. First, because cirrhosis is a risk factor for lower cure rates in people living with HIV and HCV, it is imperative to diagnose the patient and link them to a cure before the development of advanced fibrosis.
Next, although the response rates were lower in the cirrhotic coinfected cohort, the vast majority of individuals treated were still cured, so the presence of these risk factors should not deter providers in offering HCV therapy.
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