Hepatitis C Virus (HCV) Direct-Acting Antiviral Therapy in Persons With Human Immunodeficiency Virus–HCV Genotype 1 Coinfection Resulting in High Rate of Sustained Virologic Response and Variable in Normalization of Soluble Markers of Immune Activation

The Journal of Infectious Diseases, October 2020

Coinfection with hepatitis C virus (HCV) is common among people living with HIV. Prior to the advent of HCV direct acting antivirals (DAAs), coinfection was a major cause of liver-related morbidity and mortality, including cirrhosis, liver failure and hepatocellular carcinoma. Fortunately, DAAs lead to sustained virologic response (SVR), or cure, in most patients and has been linked to decreased mortality and cancer. HCV infection is also associated with other non-hepatic conditions including cardiovascular disease, Parkinson’s disease, and type 2 diabetes mellitus. While the causal relationship between HCV infection and these conditions is not fully established, it may be partly explained by HCV-induced systemic inflammation, which has been associated with immune dysfunction, morbidity, and mortality.

In order to better understand the role of inflammation, study A5329 evaluated the safety, tolerability, and efficacy of HCV treatment with paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD) with or without ribavirin (RBV) in virally suppressed people living with HIV HCV genotype-1 coinfection. Researchers examined changes in plasma inflammatory markers, including soluble CD14 (sCD14), Interferon Induced Protein 10 (IP10), soluble CD163 (sCD163), Interleukin-6 (IL-6), Interleukin 18 (IL-18), Monocyte Chemoattractant Protein 1 (MCP1), Autotaxin (ATX), and Macrophage-2-Binding-Protein (Mac2BP), over the course of treatment.

SVR rate was 93%. At baseline, cirrhosis was associated with higher ATX and MCP1, women had higher ATX and IL-6, older age was associated with higher Mac2BP, higher BMI was associated with higher ATX, and HIV-1 protease inhibitor use was associated with higher sCD14. Among those who experienced SVR, IP-10, ATX, and Mac2BP declined by week two, IL-18 declined by the end of treatment, sCD14 did not change, and sCD163, MCP1, and IL-6 levels only changed at a single time point.

These findings indicate that markers of immune activation in HIV hepatitis C coinfection are likely partly attributable to age, sex, cirrhosis, BMI, and/or kind of antiretroviral therapy. Paritaprevir/ritonavir-ombitasvir-dasabuvir is a highly effective regimen that is associated with variable declines in immune activation markers.

Editor’s Clinical Impact Statement: This study confirms the importance of treating hepatitis C to lower inflammation in the body.

Anthony, D. D., Sulkowski, M. S., Smeaton, L. M., Damjanovska, S., Shive, C. L., Kowal, C. M., Cohen, D. E., Bhattacharya, D., Alston-Smith, B. L., Balagopal, A., & Wyles, D. L. (2020). Hepatitis C Virus (HCV) Direct-Acting Antiviral Therapy in Persons With Human Immunodeficiency Virus-HCV Genotype 1 Coinfection Resulting in High Rate of Sustained Virologic Response and Variable in Normalization of Soluble Markers of Immune Activation. The Journal of Infectious Diseases222(8), 1334–1344. https://doi.org/10.1093/infdis/jiaa254