Hepatitis B virus reactivation during belatacept treatment after kidney transplantation.

We report a case of HBV reactivation following belatacept treatment in a patient who underwent kidney transplantation in 2015 for HIV-associated nephropathy (HIVAN). Human immunodeficiency virus viral load was undetectable prior to transplantation, and CD4+ lymphocyte count was greater than 300/mL. Baseline HBV serology at transplantation was HBsAg negative, anti-HBcAb positive, anti-HBsAb 312 UI/L, and HBeAg negative/anti-HBeAb positive. Liver function tests were normal, and viral DNA was undetectable. Two years later, the patient presented with severe acute hepatitis after a progressive disappearance of anti-HbsAb, quickly followed by HBV reactivation. Immunosuppressive treatment was drastically reduced, and treatment with entecavir was started. The outcome was favorable, and HBV DNA became undetectable after 9 weeks of treatment. This is the first report of acute hepatitis related to HBV reactivation in a kidney transplant recipient treated with belatacept. The risk for HBV reactivation in patients treated with belatacept should not be underestimated, especially in those with resolved HBV infection.

Initiation of rilpivirine, tenofovir and emtricitabine (RPV/TDF/FTC) regimen in 363 patients with virological vigilance assessment in 'real life'.

OBJECTIVES: To study the single-tablet regimen (STR) combination rilpivirine/tenofovir/emtricitabine (RPV/TDF/FTC) as soon as it became available. We describe a 14 month follow-up in a real clinical setting with a focus on resistance to RPV/TDF/FTC and polymorphisms associated with these drugs. METHODS: We estimated drug resistance at STR baseline by combining all available resistance tests, resulting in a cumulative virtual genotype. Physicians were advised of current or archived resistance mutations for the three drugs. Virological response was analysed according to resistance genotype at baseline. RESULTS: Three hundred and sixty-three patients received RPV/TDF/FTC; 79% had received previous treatment and RPV/TDF/FTC was the result of a switch of one drug to rilpivirine in two-thirds of cases. The cumulative genotype showed 4% of rilpivirine resistance mutations at baseline and 16% of polymorphisms concerning non-nucleoside reverse transcriptase inhibitors (NNRTIs). With a median duration of STR of 8 months, 78% of patients with these polymorphisms were virologically suppressed compared with 96% with wild-type genotypes. Five genotypes were determined during the follow-up, revealing three rilpivirine resistance-associated mutations: E138Q/Y181I, M230L and K101P (potentially with a K101Q intermediate). CONCLUSIONS: This observational study reflects routine clinical practice and the relevance of virological advice. It also confirms the efficacy of this STR (RPV/TDF/FTC) for naive and virologically suppressed pretreated patients with a low prevalence of virological failure and resistance if the cumulative baseline genotype is free of resistance to NNRTIs and/or polymorphisms associated with NNRTIs.

Association of killer cell immunoglobulin-like receptor genes with Hodgkin's lymphoma in a familial study.

BACKGROUND: Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study. METHODOLOGY: We included 90 families with 90 HL index cases (age 16-35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families. PRINCIPAL FINDINGS: Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23-0.85] and 0.42[0.21-0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18-71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells. CONCLUSIONS: This work defines a template for family-based association studies based on full genotypic information for the KIR cluster, and provides the first evidence that activating KIRs can have a protective role in HL.