Efficacy and safety of α-interferon treatment for chronic hepatitis C in HIV-infected patients

Soriano, Vincent; García‐Samaniego, J.; Bravo, R.; Castro, Ángeles; Odriozola, Pedro Martínez; González, Juan; Colmenero, M.; Carballo, E.; Suárez, Dolores; Llibre, Josep M.; Alberdi, J.; Pedreira, José; González-Lahoz, Juan

doi:10.1016/s0163-4453(95)91178-2

Cited by 43 publications

(23 citation statements)

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“…Among these, the development of lymphopenia often limits its use, particularly in those patients who have received aggressive chemotherapy or who have T-cell depletion, such as that associated with chronic HIV infection. 9,11,12,38 On the other hand, the administration of recombinant IL-7 in several recent phase I/II trials in either cancer patients after aggressive chemotherapy or in HIV-infected patients under HAART [19][20][21] demonstrated good tolerance and high efficiency. Recombinant glycosylated simian IL-7 therapy elicited a significant and prolonged increase in circulating T-cell numbers, increased thymic output, and diversification of T-cell repertoire.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In addition, IFN-␣ treatment causes a leukopenia, including a decrease of lymphocyte numbers and thus of CD4 count, often leading to premature treatment interruption. [8][9][10][11][12] Therefore, to enhance the efficiency of anti-HVC therapy in coinfected patients, it is critically important to develop an alternative treatment that limits the lymphopenic effect of IFN-␣ therapy.Interleukin 7 (IL-7), a cytokine that promotes precursor B-and T-cell maturation [13][14][15] and supports peripheral T-cell homeostasis, [16][17][18] is currently in phase I/II trials in patients with persistent lymphopenia. This therapy has demonstrated its efficacy in restoring circulating CD4 ϩ T-cell counts in HAART-treated HIV-infected patients 19,20 as well as in increasing T-cell diversity in patients under chemotherapy for cancer.…”

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confidence: 99%

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Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques

Parker

Dutrieux

Beq

et al. 2010

Blood

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Interferon-␣ (IFN-␣)-based therapy ispresently the standard treatment for hepatitis C virus (HCV)-infected patients. Despite good effectiveness, this cytokine is associated with major side effects, including significant lymphopenia, that limits its use for HIV/HCV-coinfected patients. Interleukin-7 (IL-7) has recently shown therapeutic potential and safety in several clinical trials designed to demonstrate T-cell restoration in immunodeficient patients. The purpose of this study was to evaluate, in simian immunodeficiency virus-infected rhesus macaques, the relevance of IL-7 therapy as a means to overcoming IFN-␣-induced lymphopenia. We showed that low-dose IFN-␣ treatment induced strong lymphopenia in chronically infected monkeys. In contrast, high-dose IFN-␣ treatment stimulated IL-7 production, leading to increased circulating T-cell counts. Moreover, IL-7 therapy more than abrogated the lymphopenic effect of low-dose IFN-␣. Indeed, the association of both cytokines resulted in increased circulating T-cell IntroductionCoinfection with HIV and hepatitis C virus (HCV) has become an increasingly common occurrence, with an estimated 25% to 30% of HIV ϩ patients also being HCV ϩ . 1 As a consequence, since the appearance of highly active antiretroviral therapy (HAART), chronic liver disease has become one of the most common causes of morbidity and mortality in HIV patients. 2,3 Although the effectiveness of standard HCV treatment, based on interferon-␣ (IFN-␣) injections, is known to decrease the longer a patient has been infected with the virus, HCV patients are not systematically put under treatment. Rather, initiation of treatment depends on the state of the patient's liver (fibrosis markers, serum aminotransferases, HCV RNA, hepatitis B virus status) and other parameters, which in turn are used to determine whether the potential benefits of therapy outweigh the risks of treatment-related toxicity. 4 For HIV-HCV-coinfected patients, some of these parameters are: the assessment of HIV disease status, such as current and past opportunistic infections, HIV-associated malignancies, CD4 count, HIV viral load, and details of HAART therapy, with CD4 count being one of the main criteria. Unfortunately, coinfected patients are poor responders to standard treatment as a sustained viral response occurs in only 27% to 40% of these patients, approximately half the rate seen in HCV-monoinfected patients. [5][6][7] The main reason for this difference can be attributed to exhaustion of the immune system. In addition, IFN-␣ treatment causes a leukopenia, including a decrease of lymphocyte numbers and thus of CD4 count, often leading to premature treatment interruption. [8][9][10][11][12] Therefore, to enhance the efficiency of anti-HVC therapy in coinfected patients, it is critically important to develop an alternative treatment that limits the lymphopenic effect of IFN-␣ therapy.Interleukin 7 (IL-7), a cytokine that promotes precursor B-and T-cell maturation [13][14][15] and supports peripheral T-cell homeostasis, [16][17][18...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques

Parker

Dutrieux

Beq

et al. 2010

Blood

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“…In one study of 12 patients who had high CD4 lymphocyte counts and were treated with interferon, only one patient (8.3%) had a sustained complete response after 12 months [49]. A prospective, controlled trial of 78 patients [50] showed a complete response after 8 months of therapy in 38% of coinfected patients and 47% of HIV-negative patients. This study, in addition to others, showed a positive correlation between CD4 cell counts and response to therapy.…”

Section: Therapymentioning

confidence: 99%

HIV and hepatitis virus infection

Poles

Dieterich

2000

Curr Infect Dis Rep

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“…Several studies have demonstrated that treatment of co-infected patients with IFN alfa leads to a low percentage of sustained responses that are comparable to responses in patients infected with HCV alone [32,33]. One caveat is that the majority of these studies involved patients with relatively minor degrees of immunosuppression by HIV.…”

Section: Interferon/ribavirin Therapymentioning

confidence: 99%

Issues in HIV/hepatitis C co-infection

Moorman

2001

Curr Infect Dis Rep

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Co-infection of patients with hepatitis C virus (HCV) and HIV is prevalent. HCV disease is clearly exacerbated in the setting of HIV disease, and the long-term effects of HCV have become an increasing concern as patients live longer on highly active antiretroviral therapy. Although treatment for HCV disease is evolving rapidly, its role in the HIV-infected patient is not well delineated. This review will focus on the major issues in the HIV/HCV co-infected patient and discuss therapy for HCV in the era of highly active antiretroviral therapy.

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Efficacy and safety of α-interferon treatment for chronic hepatitis C in HIV-infected patients

Cited by 43 publications

References 18 publications

Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques

Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques

HIV and hepatitis virus infection

Issues in HIV/hepatitis C co-infection

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