Effects of the genetic pattern defined by low-density lipoprotein receptor and IL28B genotypes on the outcome of hepatitis C virus infection.

The aim of this study was to assess the impact of the genetic pattern (GP) defined by the single nucleotide polymorphisms (SNPs) rs14158 of low-density lipoprotein receptor (LDLR) and rs12979860 of interleukin-28B (IL28B) genes on the outcome and features of hepatitis C virus (HCV) infection in patients with and without human immunodeficiency virus (HIV) coinfection. 314 HIV/HCV-coinfected and 109 HCV-monoinfected patients treated with pegylated interferon (Peg-IFN) plus ribavirin (RBV), as well as 51 patients with HCV spontaneous clearance (SC), were included. Variations in both SNPs were determined by the TaqMan polymerase chain reaction (PCR) assay. In the 286 patients chronically infected by HCV genotypes 1 or 4, both rs14158 CC and rs12979860 CC were associated with a higher rate of sustained virological response (SVR), and these effects were complementary in both HCV-monoinfected and HIV/HCV-coinfected patients. Thus, 24 % of patients with rs14158/rs12979860 TT-TC/TT-TC, 33 % with TT-TC/CC, 44.2 % with CC/TT-TC, and 75.8 % harboring CC/CC attained SVR (p < 0.001). SC was associated with the IL28B genotype (66.7 % CC in SC vs. 42.6 % among those with chronic infection, p < 0.001) but not with the LDLR genotype. There was no association between GP and the plasma level of alanine aminotransferase (ALT) or the presence of advanced fibrosis. There is a complementary effect between the IL28B and LDLR genotypes on the probability of achieving SVR after Peg-IFN/RBV therapy in patients with HCV 1 or 4. Thus, the predictive value of IL28B genotype is modulated by the LDLR genotype in both HCV-monoinfected and HIV/HCV-coinfected patients. This complementary effect of both genotypes is also observed on the plasma levels of low-density lipoprotein cholesterol (LDL-C).

Level, phenotype and activation status of CD4+FoxP3+ regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus.

CD4(+) regulatory T (T(reg)) cells have been involved in impaired immunity and persistence of viral infections. Herein, we report the level, phenotype and activation status of T(reg) cells in patients chronically infected with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). Expression of CD25, CD45RA, CD27, CD127 and CD38 was assessed on these cells using polychromatic flow cytometry in 20 healthy controls, 20 HIV-monoinfected, 20 HCV-monoinfected and 31 HIV/HCV-co-infected patients. T(reg) cells were defined as CD4(+)forkhead box P3 (FoxP3)(+). The percentage of T(reg) cells was increased significantly in HIV patients compared with controls. Moreover, there was a significant inverse correlation between CD4 counts and T(reg) cell levels. Fewer than 50% of T(reg) cells expressed CD25, with differences in terms of CD127 expression between CD25(+) and CD25((-)) T(reg) cells. CD4(+)Foxp3(+) T(reg) cells displayed predominantly a central memory phenotype (CD45RA(-)CD27(+)), without differences between patients and healthy controls. Activated T(reg) cells were increased in HIV patients, particularly considering the central memory subset. In summary, HIV infection, but not HCV, induces an up-regulation of highly activated T(reg) cells, which increases in parallel with CD4 depletion. Hypothetically, this might contribute to the accelerated course of HCV-related liver disease in HIV-immunosuppressed patients.

Lack of an association between the ASN-108 mutation in the dihydrofolate reductase gene and in vivo resistance to sulfadoxine/pyrimethamine in Plasmodium falciparum.

Sulfadoxine/pyrimethamine (SP) is considered an alternative treatment for acute uncomplicated malaria caused by Plasmodium falciparum resistant to chloroquine. However, the appearance of resistance to this drug has been reported since its initial use in Colombia. Molecular analysis of the dihydrofolate reductase gene indicates a correlation between in vitro resistance to SP and the Asn-108 point mutation. Little is known about the association of this point mutation and in vivo resistance to SP. We used a mutation-specific polymerase chain reaction strategy to analyze the presence of the Asn-108 point mutation in 48 clinical samples with adequate clinical response (ACR), 2 early treatment failures (ETF), and 1 late treatment failure (LTF). The Asn-108 mutation was detected in 36 of the ACR samples and in all of the ETF and LTF samples. Eleven ACR samples amplified with the wild-type-specific primer and one amplified with the primer for the Thr-108 mutation described for resistance to cycloguanil. These results suggest that the Asn-108 marker may not be useful in predicting SP treatment failure.