Abstract:
OBJECTIVE:The lipodystrophy syndrome is a major adverse effect of highly active antiretroviral therapy (HAART), associated with altered circulating levels and adipose tissue mRNA expression of proinflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF)alpha, and adiponectin. Proinflammatory cytokines and adiponectin, which are secreted by adipose tissue, regulate fat metabolism, insulin sensitivity and adipose cell apoptosis. We examined the direct effects of individual antiretrovirals on lipid metabolism and cytokine and adiponectin production by cultured adipocytes. METHODS:Differentiating 3T3-F442A cells and differentiated 3T3-L1 adipocytes were treated for 12 or 4 days, respectively, with protease inhibitors (PIs) indinavir, nelfinavir, amprenavir, lopinavir and ritonavir, or nucleoside reverse transcriptase inhibitors (NRTIs) stavudine and zidovudine, at near-Cmax concentrations. Lipid metabolism was estimated by Oil Red O staining of intracellular lipids, mRNA expression of fatty acid synthase and adipocyte lipid binding protein 2, and insulin activation of lipogenesis. Apoptosis was estimated by flow cytometry. The expression and secretion of proinflammatory cytokines (IL-6, TNFalpha and IL-1beta) and adiponectin were evaluated by real-time reverse transcription PCR and ELISA. RESULTS:Chronic treatment of 3T3-F442A differentiating adipocytes and differentiated 3T3-L1 adipocytes with PIs and NRTIs reduced lipid accumulation, mRNA expression of lipid markers and insulin-induced lipogenesis. IL-6, TNFalpha, IL-1beta and adiponectin expression and secretion were markedly altered in differentiating 3T3-F442A adipocytes. PIs had either no effect on differentiated 3T3-L1 adipocytes (TNFalpha expression and sucretion) or their effect was less marked than in 3T3-F442A cells. Indinavir and amprenavir did not alter cytokine secretion and expression by mature adipocytes. The effects of stavudine and zidovudine on differentiating and mature adipocytes were similar, despite the difference in treatment procedure. The drugs with the strongest effect on TNFalpha expression also increased adipocyte apoptosis, in contrast to the drugs that only moderately increased TNFalpha expression. CONCLUSIONS:These results suggest that increased cytokine and decreased adiponectin secretion and expression induced by some PIs and NRTIs may contribute to the adipose tissue loss (via apoptosis and lipid leakage) and insulin resistance associated with the lipodystrophy syndrome.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Lagathu C,Bastard JP,Auclair M,Maachi M,Kornprobst M,Capeau J,Caron Msubject
Has Abstractpub_date
2004-12-01 00:00:00pages
911-20issue
6eissn
1359-6535issn
2040-2058journal_volume
9pub_type
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journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2612
更新日期:2013-01-01 00:00:00
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journal_title:Antiviral therapy
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doi:10.3851/IMP3344
更新日期:2019-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP1609
更新日期:2010-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2951
更新日期:2015-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:
更新日期:2008-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP3219
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,随机对照试验,评审
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更新日期:2013-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
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更新日期:2015-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1664
更新日期:2010-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1882
更新日期:2011-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second-line protease inhibitor (PI). METHODS:The prevalence of DRV RAMs, identified from IAS 2010 an...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2015
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:A genome-wide association study revealed an association between variants of the inosine triphosphatase (ITPA) gene and ribavirin (RBV)-induced anaemia. The aim of this study was to replicate this finding in an independent Japanese cohort and to define a method to allow pretreatment prediction of anaemia in c...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1796
更新日期:2011-01-01 00:00:00
abstract::We report the first two paediatric cases of sofosbuvir treatment during high-intensity myeloablative conditioning and engraftment phases of haematopoietic stem cell transplantation. These reports highlight the safety of sofosbuvir during all phases of transplantation and the lack of interaction between sofosbuvir and ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3332
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Researchers must often rely on creatinine measurements to assess kidney function because direct glomerular filtration rates (GFR) and cystatin-c are rarely measured in routine clinical settings. However, HIV treatments often include dolutegravir, raltegravir, rilpivirine or cobicistat, which inhibit the prox...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3373
更新日期:2020-11-19 00:00:00
abstract:BACKGROUND:CD4(+) T-cell count recovery after antiretroviral therapy (ART) initiation is associated with improved health outcomes. It is unknown how the CD4(+) T-cell counts of African HIV patients recover following ART initiation. METHODS:We examined CD4(+) T-cell count recovery in a large cohort of HIV-positive pati...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2670
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND/AIMS:We conducted a case-control study to investigate the efficacy of interferon-alpha (IFN-alpha) and ribavirin combination therapy for patients with chronic hepatitis C and B virus (HCV/HBV) coinfection and to elucidate the interaction of these two viruses. METHODS:Forty-two chronic HCV/HBV-coinfected pat...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:The potential use of variola virus as a biological weapon has renewed efforts in the development of antiviral agents against orthopoxviruses. ST-246 [4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-di oxo-4,6-ethenocycloprop [f]isoindol-2(1 H)-yl)-benzamide] is an anti-orthopoxvirus compound active ag...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:2005-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3281
更新日期:2019-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3313
更新日期:2019-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:In patients with chronic HCV infection, an association between IL28B genotype and insulin-resistance (IR), known predictors of sustained virological response (SVR) to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, has been reported. The aim of this study was to investigate the association of IR ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2743
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:There are few published data characterizing patterns of liver stiffness measurements (LSMs) among HCV-infected persons and their potential impact on clinical decisions (for example, deferring treatment and hepatocellular carcinoma surveillance). METHODS:A total of 591 HCV-infected injection drug users in a ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2085
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:IL28B genotype predicts response to treatment against HCV with pegylated interferon/ribavirin (PR) and impacts on the outcome of therapy including telaprevir (TVR). This study aimed to determine the influence of the favourable IL28B genotype on early viral kinetics during therapy with TVR/PR in HIV-HCV-coinf...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP2921
更新日期:2015-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Chronic infection with HBV or HCV can lead to the development of hepatocellular carcinoma (HCC). The major risk factors for HBV-related HCC are persistent presence of hepatitis B e antigen (HBeAg) and/or high serum HBV DNA levels, and cirrhosis. The major risk factor for HCV-related HCC is cirrhosis. One randomized do...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP1895
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:The tuberculosis (TB) mortality rate of registered TB patients in Malawi is 23%, and 59% of the deaths occur in the first 2 months of treatment. HIV-related complications appear to be an important cause. Starting antiretroviral therapy early during tuberculosis treatment may improve outcome but problems ofte...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00