T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy

Auma, Ann; Shive, Carey L.; Damjanovska, Sofi; Kowal, Corinne; Cohen, Daniel E.; Bhattacharya, Debika; Alston-Smith, Beverly; Osborne, Melissa; Kalayjian, Robert C.; Balagopal, Ashwin; Sulkowski, Mark S.; Wyles, David L.; Anthony, Donald D.

doi:10.1093/ofid/ofab079

Cited by 6 publications

(7 citation statements)

References 42 publications

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“…On the other hand, analysis of CD8+ T cells showed important changes such as an increased CD28, CD45RO, and HLA-DR expression without a concomitant decrease in CD38 for long-term follow-up outcome. These data are in contrast with those previously reported by other authors showing a reduction in immune activation induced by treatment [15,38]. The difference could be due to the sample size or the characteristic of the study population (e.g., fibrosis stage, cirrhosis, different anti-HCV treatment, DAA duration for SVR).…”

Section: Discussioncontrasting

confidence: 99%

Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy

et al. 2021

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Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. Objectives: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Materials and Methods: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). Results: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Conclusions: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients.

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Section: Discussioncontrasting

confidence: 99%

Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy

et al. 2021

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“…Chronic HCV infection is associated with elevated plasma levels of systemic markers of immune activation such as sCD14, sCD163, IL-18, Mac-2BP, ATX, and IP-10, more so in patients with advanced liver disease [ 19 – 22 ]. The levels of some markers normalize following DAA therapy initiation (such as IP-10) while other markers often remain elevated (such as sCD14) [ 19 , 23 , 24 ]. Residual immune activation following DAA therapy has been attributed to presence of liver fibrosis and cirrhosis prior to DAA treatment [ 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

Transient elastography score is elevated during rheumatoid factor-positive chronic hepatitis C virus infection and rheumatoid factor decline is highly variable over the course of direct-acting antiviral therapy

et al. 2022

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Background Elevated rheumatoid factor (RF) levels and systemic immune activation are highly prevalent during chronic hepatitis C virus (HCV) infection. Direct-acting antiviral (DAA) therapy has been associated with normalization of various soluble immune activation parameters. Whether the RF levels relate to soluble immune activation markers during chronic HCV infection, and over what time frame RF levels normalize during and after DAA treatment is unknown and was investigated here. Methods In a longitudinal study, plasma and serum was obtained from HCV infected RF positive (RF+) and RF negative (RF-) participants. The levels of RF, HCV RNA and soluble markers of inflammation were determined before (week 0), during (weeks 4, 8 and 12) and after (week 24) treatment with HCV DAA therapy. In a subset of RF+ participants, the analysis was extended to over 70 weeks after therapy initiation. Hepatic and other clinical parameters were determined at baseline (week 0) in all participants. Results Before therapy, transient elastography (TE) score was greater in RF+ compared to RF- HCV infected participants, while the systemic levels of soluble inflammatory markers were comparable. Following DAA therapy initiation, HCV RNA levels became undetectable within 4 weeks in both the RF+ and RF- groups. RF levels declined in the first 6 months in most RF+ persons but most commonly remained positive. The levels of some soluble inflammatory markers declined, mainly within 4 weeks of DAA therapy start, in both the RF+ and RF- groups. The baseline (week 0) TE score correlated with RF levels before, during and after DAA therapy, while plasma IL-18 levels correlated with RF level after DAA therapy. Conclusion During chronic HCV infection, TE score is elevated in RF+ HCV infected individuals and factors other than HCV viremia (including liver stiffness or fibrosis and select markers of inflammation) likely contribute to persistence of RF after treatment of HCV with DAA.

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“…In this regard, a recent report evaluating T-cell and monocyte activation over the course of HCV direct-acting antiviral (DAA) therapy in HCV/HIV coinfection [ 39 ] showed that after therapy CD4 T-cell activation positively correlated with monocyte activation. This phenomenon did not exist before DAAs therapy and was possibly related to restored liver function or residual immune activation.…”

Section: Discussionmentioning

confidence: 99%

Risk of HIV viral rebound in HIV infected patients on direct acting antivirals (DAAs) treatment for HCV

et al. 2022

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Background The dynamic of HIV-viral load (VL) remains poorly investigated in HIV/HCV patients under direct acting antivirals (DAAs). Methods We retrospectively evaluated HIV-VL at baseline (BL) during and up to 24 weeks post-DAAs in a cohort of 305 HIV-1/HCV patients, on ART and with no HIV virological failure (VF) in the 6 months before treatment with DAAs; during the period of observation VF was defined as confirmed VL≥50 copies/mL; virological blips (VB, transient, not confirmed, VL ≥50 copies/mL). Stepwise Cox regression models were fitted to estimate adjusted hazard ratios (aHR) of VF. Results Fifteen VF occurred in 13 patients over 187 person-years of follow-up (PYFU): incidence rate (IR) of 8.0 per 100-PYFU (95% CI = 4.0–12.1); 29 VBs were detected in 26 patients over 184 PYFU: IR = 15.8 per 100-PYFU (95% CI = 10.0–21.5). The most prominent factor associated with VF was the presence of BL HIV residual viremia (RV = HIV-RNA detectable but not precisely quantifiable) [aHR = 12.26 (95% CI = 3.74–40.17), P<0.0001]. Other factors were ≥1 VBs in the 6 months before DAAs [aHR = 6.95 (95% CI = 1.77–27.37) P = 0.006] number of ART regimens failed before DAAs initiation [aHR (per more regimen) = 1.22 (95% CI = 1.04–1.42), P = 0.012] and age [aHR (per year older) = 1.16 (95% CI = 1.04–1.29), P = 0.010]. Conclusions Our findings underline the importance for close monitoring HIV-VL in selected patients. Whether this phenomenon is triggered by the rapid clearance of HCV remains to be established.

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T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy

Cited by 6 publications

References 42 publications

Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy

Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy

Transient elastography score is elevated during rheumatoid factor-positive chronic hepatitis C virus infection and rheumatoid factor decline is highly variable over the course of direct-acting antiviral therapy

Risk of HIV viral rebound in HIV infected patients on direct acting antivirals (DAAs) treatment for HCV

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