Exposure to TDF is associated with an increased risk over time of kidney tubular abnormalities in the absence of significant impaired glomerular function. Although long-term consequences of this tubulopathy are unknown, close monitoring of accelerated bone mineral loss and renal insufficiency are warranted. Periodic screening of tubular function parameters should be recommended to patients receiving TDF.
Background
Given that peginterferon–ribavirin treatment is poorly tolerated, there is interest in the identification of predictors of response, particularly in HIV/hepatitis C virus (HCV)-coinfected patients that respond less than HCV-monoinfected individuals. A single nucleotide polymorphism (SNP) near the IL28B gene (rs12979860) has been shown to predict treatment response in HCV-monoinfected patients carrying genotype 1. Information is lacking for HIV/HCV-coinfected individuals and/or other HCV genotypes.
Methods
From 650 HIV/HCV-coinfected patients, we identified those who had completed a course of peginterferon–ribavirin therapy with a validated outcome and available repository DNA. The rs12979860 SNP was examined in a blinded fashion.
Results
A total of 164 patients were included in the final IL28B genotyping analysis, 90 (55%) of whom achieved sustained virological response (SVR). HCV genotype distribution was as follows: HCV-1 58%, HCV-3 31% and HCV-4 11%. Overall, the SVR rate was higher in patients with CC than in those CT/TT genotypes: 56 of 75 (75%) versus 34 of 89 (38%) (P <0.0001). The effect of the SNP was seen in HCV genotypes 1 and 4 but not in HCV genotype 3 carriers. In the multivariable analysis (odds ratio; 95% confidence interval; P value), the rs12979860 CC genotype was a strong predictor of SVR (3.7; 1.6–8.5; 0.002), independent of HCV genotype 3 (8.0; 3.1–21.0; <0.001), serum HCV-RNA less than 600 000 IU/ml (11.9; 3.8–37.4; <0.001) and lack of advanced liver fibrosis (3.5; 1.4–8.9; 0.009).
Conclusion
The rs12979860 SNP located near the IL28B gene is associated with HCV treatment response in HIV-infected patients with chronic hepatitis C due to genotypes 1 or 4. Thus, IL28B genotyping should be considered as part of the treatment decision algorithm in this difficult-to-treat population.
Liver damage may result from multiple factors in HIV-infected patients. The availability of reliable noninvasive tools to measure liver fibrosis has permitted the screening of large patient populations. Cross-sectional study of all consecutive HIV outpatients who underwent examination by transient elastometry (FibroScan) at one HIV reference clinic during 2007. Advanced liver fibrosis (ALF) was defined as hepatic stiffness >9.5 kilopascals, which corresponds to Metavir stages F3-F4 in the liver biopsy. A total of 681 consecutive HIV-infected patients (64% injecting drug users; mean age 43; 78% male; 98% on antiretroviral therapy) had at least one valid FibroScan evaluation. ALF was diagnosed in 215 (32%) of them. In the univariate analysis, ALF was significantly associated with older age, low CD4 counts, chronic hepatitis C, past alcohol abuse, elevated ALT, high triglycerides, low cholesterol, high homeostasis model assessment (HOMA) index and exposure to didanosine and/or stavudine. In a multivariate model (OR, 95% CI), chronic hepatitis C (2.83, 1.57-5.08), past alcohol abuse (2.26, 1.37-3.74), exposure to didanosine and/or stavudine (1.85, 1.14-3.01), high HOMA index (1.25, 1.04-1.51), older age (1.09, 1.05-1.14) and elevated ALT (1.04, 1.03-1.06) remained as independently associated with ALF. Therefore, in addition to chronic hepatitis C and alcohol abuse, insulin resistance and/or exposure to dideoxy-nucleosides may contribute to ALF in HIV-infected patients.
Tenofovir (TFV) is a nucleotide analogue active against HIV and hepatitis B virus. Although TFV rarely affects the glomerular function, abnormalities in the kidney tubular function appear to be quite common. The relationship between TFV exposure and kidney tubular dysfunction (KTD) was examined prospectively in 92 HIV-infected individuals. Median TFV plasma trough concentration was higher in patients with KTD than in the rest (182 vs. 106 ng/ml; P = 0.001). This dose-dependent effect further supports an involvement of TFV in KTD.
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