T‐lymphocyte populations in hepatitis C and HIV co‐infected patients treated with interferon‐alfa‐2a and ribavirin

Néau, Didier; Galpérine, Tatiana; Legrand, E.; Pitard, Vincent; Néau-Cransac, Martine; Jf, Moreau; Ragnaud, JM; Dupon, M.; Fleury, Hervé; Lafon, M-E

doi:10.1046/j.1468-1293.2003.00140.x

Cited by 10 publications

(8 citation statements)

References 39 publications

(41 reference statements)

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“…Both coinfected and monoinfected groups experienced a drop in CD4+ on treatment through week 48, with three patients reaching levels <200 cells/mm 3 . This has been noted previously 29. Monoinfected patients, however, had a strong CD4+ rebound after treatment, whereas coinfected patients remained generally at depressed levels.…”

Section: Discussionsupporting

confidence: 80%

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Hunt

Keyomarsi

2005

Cancer

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Section: Discussionsupporting

confidence: 80%

Author reply

Hunt

Keyomarsi

2005

Cancer

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“…This has been noted previously. 29 Monoinfected patients, however, had a strong CD4ϩ rebound after treatment, whereas coinfected patients remained generally at depressed levels. Although too few patients were assessed at week 72 to determine the relationship between CD4ϩ rebound and sustained viral clearance, GEE models of changes in CD4ϩ over time demonstrated a significant and positive relationship between CD4ϩ lymphocyte counts and HCV viral load, suggesting that when treatment is effective, lymphopenia is more likely.…”

Section: Discussionmentioning

confidence: 96%

HCV kinetics, quasispecies, and clearance in treated HCV-infected and HCV/HIV-1-coinfected patients with hemophilia

et al. 2006

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Hepatitis C virus (HCV) treatment response rates remain low in HCV/HIV-1-coinfected individuals compared with those with HCV alone. Persons with inherited coagulation disorders have high rates of HCV and HIV-1 infection, but HCV treatment trials in this patient population are scarce. We hypothesized that differences by infection status in HCV viral kinetics would be associated with differences in HCV quasispecies complexity over time and with treatment response disparities. Coinfected and monoinfected patients were enrolled in a treatment trial for pegylated-interferon alpha-2a (peg-IFN) ؉ ribavirin. Patients were treated for 48 weeks and followed for an additional 24. Quantitative HCV RNA was tested at multiple times during and after treatment. Viral kinetic parameters associated with response were estimated with a mathematical model. Quasispecies emergence was determined via heteroduplex complexity assay. Twenty-two patients were HCV RNA-positive at baseline, with no significant demographic or virological differences by infection status. Five of eleven (45%) of monoinfected and 3 of 11 (27%) of coinfected patients achieved sustained viral response (SVR). Peg-IFN efficacy (⑀) of 90% or greater was associated with probability of end-of-treatment response (ETR) (P ‫؍‬ .001) and SVR (P ‫؍‬ .06). Patients with SVR had lower baseline quasispecies complexity than those without SVR (P ‫؍‬ .07). Those with ⑀ of 90% or greater also had lower baseline complexity (P ‫؍‬ .07). Coinfection status mediated changes in complexity over time (P ‫؍‬ .04). In conclusion, low pretreatment quasispecies complexity may predict peg-IFN response; early peg-IFN response is critical for sustained HCV clearance and is altered in coinfection. Further studies are warranted. (HEPATOLOGY 2006;44:1146-1157

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“…We herein demonstrated that IFNa-based therapy leads to major lymphocytopenia in naïve T-cell compartments, in particular in the RTE subset. Several mechanisms could be implicated in the establishment of such a lymphocytopenia [41]. Among these, enhanced apoptosis [42,43], cell sequestration in lymphoid or non-lymphoid organs [12,21,22] and regulation of peripheral T-cell homeostasis [20].…”

Section: Discussionmentioning

confidence: 99%

Altered Thymic Function during Interferon Therapy in HCV-Infected Patients

et al. 2012

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Interferon alpha (IFNα) therapy, despite good efficacy in curing HCV infection, leads to major side effects, in particular inducement of a strong peripheral T-cell lymphocytopenia. We here analyze the early consequences of IFNα therapy on both thymic function and peripheral T-cell homeostasis in patients in the acute or chronic phase of HCV-infection as well as in HIV/HCV co-infected patients. The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. Beginning with the first month of therapy, a profound lymphocytopenia was observed for all T-cell subsets, including naïve T-cells and recent thymic emigrants (RTE), associated with inhibition of intrathymic precursor T-cell proliferation. Interleukin (IL)-7 plasma concentration rapidly dropped while lymphocytopenia progressed. This was neither a consequence of higher consumption of the cytokine nor due to its neutralization by soluble CD127. Decrease in IL-7 plasma concentration under IFNα therapy correlated with the decline in HCV viral load, thymic activity and RTE concentration in blood. These data demonstrate that IFNα-based therapy rapidly impacts on thymopoiesis and, consequently, perturbs T-cell homeostasis. Such a side effect might be detrimental for the continuation of IFNα therapy and may lead to an increased level of infectious risk, in particular in HIV/HCV co-infected patients. Altogether, this study suggests the therapeutic potential of IL-7 in the maintenance of peripheral T-cell homeostasis in IFNα-treated patients.

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T‐lymphocyte populations in hepatitis C and HIV co‐infected patients treated with interferon‐alfa‐2a and ribavirin

Abstract: High-dosed IFN anti-HCV therapy induced only moderate and transient CD4 lymphopenia in HIV co-infected patients.

Cited by 10 publications

References 39 publications

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HCV kinetics, quasispecies, and clearance in treated HCV-infected and HCV/HIV-1-coinfected patients with hemophilia

Altered Thymic Function during Interferon Therapy in HCV-Infected Patients

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