Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord.

BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in HIV/HCV co-infected patients in a large European cohort collaboration, including data from different European countries. METHODS: HIV/HCV co-infected patients were included if they were aged ≥16 years, received pegIFN alfa-2a or 2b and RBV combination treatment and were enrolled in the COHERE cohort collaboration. Logistic regression was used to evaluate the impact of abacavir on achieving a sustained virologic response (SVR) to HCV treatment. RESULTS: In total 1309 HIV/HCV co-infected patients who had received HCV therapy were included, of whom 490 (37 %) had achieved an SVR. No statistically significant difference was seen for patients using ABC-containing regimens compared to patients using an emtricitabine + tenofovir (FTC + TDF)-containing backbone, which was the most frequently used backbone. In the multivariate analyses, patients using a protease inhibitor (PI)-boosted regimen were less likely to achieve an SVR compared to patients using a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen (OR: 0.61, 95 % CI: 0.41-0.91). The backbone combinations zidovudine&lamivudine (AZT + 3TC) and stavudine&lamivudine (d4t + 3TC) were associated with lower SRV rates (0.45 (0.24-0.82) and 0.46 (0.22-0.96), respectively). CONCLUSION: The results of this large European cohort study validate that SVR rates are generally not affected by ABC. Use of d4T or AZT as part of the HIV treatment regimen was associated with a lower likelihood of achieving an SVR.

Analysis of IL28B alleles with virologic response patterns and plasma cytokine levels in HIV/HCV-coinfected patients.

OBJECTIVES: To estimate the impact of interleukin 28B (IL28B) polymorphisms (rs12980275, rs8099917, rs7248668, and rs11881222) and their haplotypes on hepatitis C virus (HCV) treatment (peg-interferon-α and ribavirin) success in 324 HIV/HCV-coinfected patients. We also explore the behavior of plasma cytokine levels. DESIGN: Retrospective follow-up study. METHODS: Virologic response to HCV treatment was measured by plasma HCV viral load at different endpoints: rapid virologic response (RVR), early virologic response (EVR), end-of-treatment virologic response (ETVR) and sustained virologic response (SVR). IL28B polymorphisms were genotyped using GoldenGate assay. Finally, 13 cytokines were measured at baseline in 57 plasma samples using a multiplex immunoassay kit. RESULTS: IL28B polymorphisms were strongly associated to virologic responses (RVR, EVR, ETVR, and SVR), although only for HCV genotypes 1 and 4 (P < 0.05). Strong linkage disequilibrium was detected for rs12980275/rs11881222 (r = 0.94) and rs8099917/rs7248668 (r = 0.99). IL28B haplotypes showed association but no improvement on treatment outcome prediction. Thus, the genotyping of only one single-nucleotide polymorphism was enough for predicting treatment response in GT1/4 patients with favorable rs12980275 (AA) genotype, while for subjects harboring unfavorable genotypes, the inclusion of rs8099917 was useful (SVR increased from 31 to 45%). Moreover, patients with rs12980275 (AA) that achieved SVR showed reduced plasma levels of Th1 (IFN-γ), Th2 (IL-6 and IL-9), and proinflammatory (TNF-α) cytokines. CONCLUSION: The presence of IL28B polymorphisms was significantly associated with HCV clearance during and after HCV therapy. The evaluated cytokine profile was much more favorable in patients with rs12980275 (AA) who achieved SVR.

HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy.

OBJECTIVES: To analyze whether human leukocyte antigen (HLA)-E allelic variants are associated with and may predict response to peg-interferon (IFN) alpha and ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients. DESIGN: Retrospective follow-up study. METHODS: We studied 321 naive patients who started HCV treatment. HLA-E genotyping was performed by restriction fragment length polymorphism. A sustained virological response (SVR) was defined as undetectable plasma HCV-RNA up through 24 weeks after the end of HCV treatment. RESULTS: The HLA-E*0101 allele increased the odds of achieving SVR for all patients [adjusted odds ratio (aOR) = 2.03 (95% confidence interval, 95% CI = 1.35-3.06); P = 0.001], for HCV genotype (GT) 1/4 patients (aOR = 1.62 (95% CI = 1.03-2.54), P = 0.035), and for GT2/3 patients [aOR = 9.87 (95% CI = 2.47-31.89), P = 0.001]. For decision tree analysis, the SVR rate increased from 0 to 82.6% and then to 92.5% in GT2/3 patients when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 TT genotype, the SVR rate increased from 33.3 to 54.8% and then to 61.8% when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 GT/GG genotype, the SVR rate increased from 15.4 to 22% and then to 44% when the count of HLA-E*0101 alleles increased. The overall percentage of patients correctly classified was 73.2% and the area under the receiver operating characteristic curve (AUROC) was 0.803 ±â€Š0.024. CONCLUSION: The HLA-E*0101 allele was associated with increased odds of HCV clearance and could help to predict SVR among HIV/HCV-coinfected patients on HCV therapy. This would be helpful to avoid treatment in those less likely to respond to pegylated-interferon-alpha and ribavirin treatment.

Insulin resistance impairs response to interferon plus ribavirin in patients coinfected with HIV and hepatitis C virus.

BACKGROUND/AIMS: Controversy exists about whether insulin resistance (IR) affects response to treatment of hepatitis C. We evaluated the effect of IR on sustained virologic response (SVR) in HIV/hepatitis C virus (HCV)-coinfected patients treated with interferon plus ribavirin. METHODS: We reviewed the clinical records of HIV/HCV-coinfected patients who received interferon plus ribavirin at our institution between July 2000 and March 2007. IR was defined as a homeostasis model assessment ≥ 3.8. SVR was defined as an undetectable HCV RNA at 24 weeks after the end of treatment. Efficacy was evaluated using an on-treatment (OT) analysis. Multivariate logistic regression analysis was used to evaluate factors associated with SVR. RESULTS: During the study period, 218 patients were treated with interferon plus ribavirin; IR at baseline was available for 162 patients, and 134 were included in the OT analysis; HCV genotype (G) 1/4, 67%; F3-F4 fibrosis, 36%; IR 31%. SVR was achieved in 67 patients (50%) (79% in G 2/3 vs. 38% in G 1/4). IR was associated with a lower SVR [odds ratio (OR), 0.33; 95% confidence interval (CI): 0.15-0.72; P = 0.006). The independent variables related to SVR were genotype 2/3 (OR, 6.7; 95% CI: 2.71-16.98; P < 0.001), absence of IR at baseline (OR, 3.3; 95% CI: 1.36-8.26; P = 0.008), and nadir CD4 T-cell count (OR, 1.002; 95% CI: 1.00-1.00; P = 0.047). CONCLUSIONS: Our data suggest that IR is an important determinant of SVR in HIV/HCV-coinfected patients treated with interferon plus ribavirin. Strategies to modify IR should be explored to enhance SVR during anti-HCV therapy.