Dataset Information

Sustained long-term antiviral maintenance therapy in HCV/HIV-coinfected patients (SLAM-C).

ABSTRACT: BACKGROUND:Hepatitis C virus (HCV)/HIV coinfection treatment is suboptimal with low sustained viral response rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated interferon maintenance therapy was performed by the National Institutes of Health-funded AIDS Clinical Trials Group network. METHODS:HCV treatment-naive and nonresponding interferon-experienced subjects with confirmed HCV and HIV, CD4 >200 cells per cubic millimeter, and at least stage 1 fibrosis were enrolled and treated for 12 weeks with pegylated interferon alfa 2a 180 mcg per week (PEG) + weight-based ribavirin to determine response status. Nonresponder subjects (failure to clear HCV RNA or achieve 2-log drop) underwent liver biopsy and were randomized to receive full dose PEG or observation only for 72 weeks. Paired biopsies were evaluated by a central pathologist. RESULTS:Three hundred thirty subjects were enrolled; median age was 48 years; 43% white, 37% black, non-Hispanic; 83% male; CD4+ 498 cells per cubic millimeter; 32% were interferon experienced; 74% had entry HIV RNA <50 copies per milliliter. early virologic responder was observed in 55.9% and 42.5% achieved complete Early Viral Response (cEVR). A planned interim analysis of occurred when 84 subjects were randomized. With data on 40 paired biopsies available, a safety monitoring board stopped the trial due to lack of fibrosis progression (median = 0 Metavir units/year) in the observation arm. CONCLUSIONS:Lack of fibrotic progression in the control arm was unexpected and may represent a short-term PEG/ribavirin therapy effect, high levels of HIV viral suppression, and use of antiretroviral regimens that may be less toxic than prior generations of therapy.

SUBMITTER: Sherman KE

PROVIDER: S-EPMC3017670 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sustained long-term antiviral maintenance therapy in HCV/HIV-coinfected patients (SLAM-C).

Sherman Kenneth E KE Andersen Janet W JW Butt Adeel A AA Umbleja Triin T Alston Beverly B Koziel Margaret J MJ Peters Marion G MG Sulkowski Mark M Goodman Zachary D ZD Chung Raymond T RT

Journal of acquired immune deficiency syndromes (1999) 20101201 5

<h4>Background</h4>Hepatitis C virus (HCV)/HIV coinfection treatment is suboptimal with low sustained viral response rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated interferon maintenance therapy was performed by the National Institutes of Health-funded AIDS Clinical Trials Group network.<h4>Methods</h4>HCV treatment-naive and nonresponding interferon-experienced subjects with confirmed HCV and HIV, CD4 >200 cells per cubic ...[more]

PMID: 20921898

Similar Datasets

Project description:Background and aimsTRIM5 and TRIM22 are restriction factors involved in innate immune response and exhibit anti-viral activity. Single nucleotide polymorphisms (SNPs) at TRIM5 and TRIM22 genes have shown to influence several viral infections such as human immunodeficiency virus (HIV), hepatitis B, as well as measles and rubella vaccination. The aim of this study is to analyze whether TRIM5 and TRIM22 polymorphisms are associated with liver fibrosis inflammation-related biomarkers and response to pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/hepatitis C virus (HCV) coinfected patients.MethodsA retrospective study was performed in 319 patients who started pegIFNα/RBV therapy. Liver fibrosis stage was characterized in 288 patients. TRIM5 rs3824949 and TRIM22 polymorphisms (rs1063303, rs7935564, and rs7113258) were genotyped using the GoldenGate assay. The primary outcomes were: a) significant liver fibrosis (≥F2) evaluated by liver biopsy or transient elastography (liver stiffness values ≥7.1 Kpa); b) sustained virological response (SVR) defined as no detectable HCV viral load (<10 IU/mL) at week 24 after the end of the treatment. The secondary outcome variable was plasma chemokine levels.ResultsPatients with TRIM5 rs3824949 GG genotype had higher SVR rate than patients with TRIM5 rs3824949 CC/CG genotypes (p = 0.013), and they had increased odds of achieving SVR (adjusted odds ratio (aOR = 2.58; p = 0.012). Patients with TRIM22 rs1063303 GG genotype had higher proportion of significant liver fibrosis than patients with rs1063303 CC/CG genotypes (p = 0.021), and they had increased odds of having significant hepatic fibrosis (aOR = 2.19; p = 0.034). Patients with TRIM22 rs7113258 AT/AA genotype had higher SVR rate than patients with rs7113258 TT genotypes (p = 0.013), and they had increased odds of achieving SVR (aOR = 1.88; p = 0.041). The TRIM22 haplotype conformed by rs1063303_C and rs7113258_A was more frequent in patients with SVR (p = 0.018) and was significantly associated with achieving SVR (aOR = 2.80; p = 0.013). The TRIM5 rs3824949 GG genotype was significantly associated with higher levels of GRO-α (adjusted arithmetic mean ratio ((aAMR) = 1.40; p = 0.011) and MCP-1 (aAMR = 1.61; p = 0.003).ConclusionsTRIM5 and TRIM22 SNPs are associated to increased odds of significant liver fibrosis and SVR after pegIFNα/RBV therapy in HIV/HCV coinfected patients. Besides, TRIM5 SNP was associated to higher baseline levels of circulating biomarkers GRO and MCP-1.

Project description:The Fat Mass and Obesity-Associated Protein (FTO) gene rs9939609 single nucleotide polymorphism (SNP) has been associated with obesity, metabolic syndrome, insulin resistance (IR), and type 2 diabetes mellitus in the general population. The aim of our study was to examine for the first time the association of the rs9939609 polymorphism with metabolic disturbances, liver disease and virologic response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFN?/RBV) in human immunodeficiency virus (HIV)/HCV coinfected patients.We carried out a cross-sectional study in 261 patients, of whom 178 were subsequently treated with pegIFN?/RBV therapy. FTO rs9939609 and IFNL3 rs12980275 polymorphisms were genotyped by GoldenGate®. The main outcomes were: 1) metabolic disturbances: insulin resistance (homeostatic model assessment (HOMA-IR)) and overweight (body mass index (BMI)); 2) liver disease (Metavir score): significant fibrosis (F ?2) and steatosis (>10% fatty hepatocytes); and 3) virologic response to HCV treatment: sustained virologic response (SVR).The rs9939609 AA genotype was associated with higher values of BMI (adjusted arithmetic mean ratio (aAMR) = 1.08; 95% confidence interval (95%CI) = 1.03 to 1.14; P = 0.002) and HOMA-IR (aAMR = 1.32; 95%CI = 1.03 to 1.69; P = 0.027). Patients with an rs9939609 AA genotype had higher likelihoods of achieving values of BMI ?27.5 kg/m2 (adjusted odds ratio (aOR) = 3.46; 95%CI =1.17 to 10.21; P = 0.024), HOMA-IR ?2.5 (aOR = 2.09; 95%CI = 1.02 to 4.32; P = 0.045), significant fibrosis (aOR = 2.34; 95%CI =1.02 to 5.36; P = 0.045) and steatosis (aOR = 3.65; 95%CI = 1.29 to 10.36; P = 0.015). The rs9939609 AT/AA genotype decreased the likelihood of achieving SVR (aOR = 0.58; 95%CI = 0.34 to 0.99; P = 0.044). A decision tree was performed with the genotypes of HCV, IFNL3 and FTO. The incorporation of rs9939609 significantly improves the prediction of SVR (P <0.05). The overall accuracy was 68.2%.Patients carrying the unfavourable AT/AA genotype of rs9939609 polymorphism had higher odds of metabolic disturbances and a lower likelihood of achieving successful virologic response to HCV therapy.

Dataset Information

Sustained long-term antiviral maintenance therapy in HCV/HIV-coinfected patients (SLAM-C).

Publications

Sustained long-term antiviral maintenance therapy in HCV/HIV-coinfected patients (SLAM-C).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets