Torquetenovirus viremia for early prediction of graft rejection after kidney transplantation.

OBJECTIVES: New biomarkers reflecting the degree of immunosuppression in transplant recipients are needed to provide an optimal personalized balance between rejection and infection risks. METHODS: For this purpose, we investigated TTV viremia dynamics in 66 kidney transplant recipients followed up for two years after transplantation, in relation to BK virus infection and graft rejection. RESULTS: After transplantation, TTV viremia rose by ≥2 log10 copies/mL from baseline to month 3, then declined by ≥1 log10 copies/mL thereafter. Higher TTV viremia was associated with recipients of a deceased donor, a lower count of CD8+ T cells and a higher BKV viremia. Importantly, TTV loads were significantly lower in KTR who would later display graft rejection; indeed, patients with TTV viremia lower than 3.4 log10 copies/mL at transplantation or lower than 4.2 log10 copies/mL at month 1 had a higher risk of developing graft rejection in the two following years (hazard ratio (HR) at D0 = 7.30, p = 0.0007 and HR at M1 = 6.16, p = 0.001). CONCLUSIONS: TTV viremia measurement at early times post transplantation predicts graft rejection and would represent a useful tool to improve kidney transplant monitoring.

Parsonage-Turner syndrome due to autochthonous acute genotype 3f hepatitis E virus infection in a nonimmunocompromised 55-year-old patient.

Hepatitis E virus (HEV) infection is an emerging autochthonous disease in industrialized countries. Extra-hepatic manifestations, in particular neurologic manifestations, have been reported in HEV infection. Only a few cases of hepatitis E-associated Parsonage-Turner syndrome have been reported, and HEV genotypes were rarely determined. Here, we report the case of a Parsonage-Turner syndrome associated with an acute autochthonous HEV infection in a 55-year-old immunocompetent patient. HEV genomic RNA was detected in serum and cerebrospinal fluid samples (CSF), and molecular phylogenetic analysis of HEV was performed. The interest of this case lies in its detailed description notably the molecular analysis of HEV RNA isolated from serum and CSF. HEV infection should be considered in diagnostic investigations of neurologic manifestations associated with liver function perturbations.

Herpes simplex virus type 1 hepatitis due to primary infection in a pancreas-kidney transplant recipient.

Herpes simplex Virus (HSV) hepatitis is a rare complication of HSV-1 primary infection, with a delayed diagnosis, affecting mainly immunocompromised patients. We describe a case of HSV-1 hepatitis after primary infection occurring in the postoperative days after a pancreas-kidney transplantation. The patient presented with an unusual evolution of a persistent severe hepatitis associated with a persistent viremia (Quantitative Polymerase Chain Reaction) despite an adequate intravenous (iv) antiviral treatment. Abdominal computed tomography scan showed a miliary hepatitis. The diagnosis of HSV-1 hepatitis was confirmed by immuno-chemistry on liver biopsy. The donor was negative for anti-HSV antibodies, excluding contamination by the graft. This case report emphasizes a rather seldom risk of care-associated viral infections, predominantly in immunocompromised patients.

Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.

For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.

Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France.

OBJECTIVES: To assess the prevalence of resistance to rilpivirine and mutations at position 138 in reverse transcriptase and to identify associated epidemiological and biological characteristics. METHODS: This retrospective study included 238 patients with available HIV-1 nucleotide sequences analysed at the Laboratory of Virology at the University Hospital of Nancy between January 2011 and June 2013. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was evaluated according to the ANRS algorithm (version 23) and correlated with clinico-epidemiological and therapeutic data. The virus strains were analysed by evaluating the distance and distribution of the phylogenetic tree (MEGAv5). RESULTS: Among previously treated patients (111/238, 46.6%), 68/111 (61.3%) had received NNRTIs; all were rilpivirine-naive. The prevalence of rilpivirine resistance in the whole cohort was 12.6% (30/238), and was 10.2% (13/127) and 15.3% (17/111) in naive and pre-treated patients, respectively. The E138A mutation was the most frequent mutation associated with resistance to rilpivirine (P < 0.0001). The prevalence of the E138A mutation tended to increase over time, from 3.6% (2/55) during the first half of 2011 to 9.3% (4/43) during the first half of 2013 (P = 0.0614). Seven viral strains from seven naive male patients positive for the E138A mutation appeared in the same cluster. CONCLUSIONS: In our cohort of patients, we observed significantly increased resistance to rilpivirine, mostly because of the E138A mutation, probably due to an E138A strain circulating in newly diagnosed men who have sex with men. Taken together, our results emphasize the need to investigate the prevalence of rilpivirine resistance-associated mutations in the coming years both in France and abroad.