We report 3 cases of renal toxicity associated with use of the antiviral agent tenofovir. Renal failure, proximal tubular dysfunction, and nephrogenic diabetes insipidus were observed, and, in 2 cases, renal biopsy revealed severe tubular necrosis with characteristic nuclear changes. Patients receiving tenofovir must be monitored closely for early signs of tubulopathy (glycosuria, acidosis, mild increase in the plasma creatinine level, and proteinuria).

We analyzed the factors and outcome of patients with disseminated adenovirus infection (dAdV) after allogeneic hematopoeitic stem cell transplantation (HSCT). Thirty patients with dAdV were identified among 620 allogeneic HSCT recipients. Primary diseases were leukemia (n=17), Fanconi anemia (n=12) or others (n=1). Source of stem cells was unrelated in 28 and related in 2 patients. The graft consisted of peripheral blood (n=3), bone marrow (n=12) and unrelated cord-blood (UCB, n=15). Risk factors for dAdV in unrelated HSCT recipients were previous Fanconi disease (p=0.03) and GVHD (p=0.02) in children, and cord blood source of stem cells (p=0.029) and GVHD (0.024) in adults.

Aspergillus ustus is an uncommon clinical species which is poorly susceptible to antifungals. We report two cases of A. ustus infections that occurred in allogeneic stem cell transplant recipients while they were receiving either voriconazole or caspofungin. Prolonged use of these new antifungal agents may increase the risk of the emergence of resistant organisms. CASE REPORTPatient 1 was a 29-year-old male, weighing 80 kg, who was diagnosed with acute lymphoblastic leukemia in October 2002. During initial chemotherapy-induced neutropenia, he developed fever, cough, and nodular pulmonary infiltrates visible by computed tomography (CT) scan, suggestive of possible lunginvasive aspergillosis (2). Cultures of sputum were negative for Aspergillus, and Aspergillus antigenemia (Platelia Aspergillus assay; Bio-Rad, Marnes-la-Coquette, France) remained negative (index Ͻ 0.5). Treatment with oral voriconazole (200 mg twice a day after the loading dose) was initiated on 22 December 2002. Granulocyte recovery occurred 4 days later and was associated with the complete resolution of pulmonary lesions. A myeloablative genoidentical hematopoietic stem cell transplant (HSCT) was performed during the first complete remission, on 13 March 2003. A pre-HSCT lung CT scan revealed no abnormality. Voriconazole was continued as a secondary prophylaxis. Between April 2003 and January 2004, the patient experienced three episodes of severe graft-versus-host disease (GVHD), which were treated with cyclosporine, an increased dosage of steroids, and mycophenolate mofetil. In September 2003, the patient, who was afebrile, developed several necrotic cutaneous lesions for which he was admitted to the hospital. The chest CT scan revealed a nonspecific infiltrate in the right inferior pulmonary lobe. Mycological examination of a cutaneous biopsy specimen revealed septate and branched hyphae consistent with Aspergillus spp. A culture yielded Aspergillus ustus, which was identified by morphological methods, with confirmation by sequencing of the ITS1-5.8S-ITS2 region (Fig. 1). Cultures of sputum were also positive for A. ustus. Several Aspergillus antigenemia tests were positive, with galactomannan index values of up to 3. Voriconazole was discontinued, and amphotericin B deoxycholate (1 mg/kg of body weight/day) was started. Six days later, the patient developed right-leg paresis. Brain magnetic resonance imaging (MRI) revealed a single frontal lesion compatible with aspergillosis. Treatment was switched to liposomal amphotericin B (3 mg/kg/day) and caspofungin (70 mg/day). The patient clinically improved, with complete regression of both cutaneous lesions and neurological abnormalities. Subsequent brain MRIs showed progressive regression of the lesion with scar formation. Subsequent lung CT scans showed a size decrease and excavitation of the pulmonary lesion. Aspergillus antigenemia decreased and remained negative after 18 December 2003. The patient later experienced several episodes of hemoptysis. Fungal hyphae compatible with a zygomycete wer...

BackgroundThe European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV‐positive persons in geographically diverse areas.Guideline highlightsMajor revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management. Recommendations on the clinical situations in which tenofovir alafenamide may be considered over tenofovir disoproxil fumarate are provided, and recommendations on which antiretrovirals can be used safely during pregnancy have been revised. Renal and bone toxicity and hepatitis C virus (HCV) treatment have been added as potential reasons for ART switches in fully virologically suppressed individuals, and dolutegravir/rilpivirine has been included as a treatment option. In contrast, dolutegravir monotherapy is not recommended. New recommendations on non‐alcoholic fatty liver disease, chronic lung disease, solid organ transplantation, and prescribing in elderly are included, and human papilloma virus (HPV) vaccination recommendations have been expanded. All drug–drug interaction tables have been updated and new tables are included. Treatment options for direct‐acting antivirals (DAAs) have been updated and include the latest combinations of sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Recommendations on management of DAA failure and acute HCV infection have been expanded. For treatment of tuberculosis (TB), it is underlined that intermittent treatment is contraindicated, and for resistant TB new data suggest that using a three‐drug combination may be as effective as a five‐drug regimen, and may reduce treatment duration from 18‐24 to 6‐10 months.ConclusionsVersion 9.0 of the EACS Guidelines provides a holistic approach to HIV care and is translated into the six most commonly spoken languages.

Mismatched unrelated donor (MMUD) or umbilical cord blood (UCB) can be chosen as alternative donors for allogeneic stem cell transplantation but might be associated with long-lasting immune deficiency. Sixty-six patients who underwent a first transplantation from either UCB (n = 30) or 9/10 MMUD (n = 36) and who survived beyond 3 months were evaluated. Immune reconstitution was prospectively assessed at sequential time points after transplantation. NK, B, CD4(+), and CD8(+) T cells and their naïve and memory subsets, as well as regulatory T cells (Treg), were studied. Detailed analyses on infections occurring after 3 months were also assessed. The 18-month cumulative incidences of infection-related death were 8% and 3%, and of infections were 72% and 57% after MMUD and UCB transplantation, respectively. Rates of infection per 12 patient-month were roughly 2 overall (1 for bacterial, .9 for viral, and .3 for fungal infections). Memory, naïve CD4(+) and CD8(+)T cells, naïve B cells, and Treg cells reconstitution between the 2 sources were roughly similar. Absolute CD4(+)T cells hardly reached 500 per μL by 1 year after transplantation and most B cells were of naïve phenotype. Correlations between immune reconstitution and infection were then performed by multivariate analyses. Low CD4(+) and high CD8(+)T cells absolute counts at 3 months were linked to increased risks of overall and viral (but not bacterial) infections. When assessing for the naïve/memory phenotypes at 3 months among the CD4(+) T cell compartment, higher percentages of memory subsets were protective against late infections. Central memory CD4(+)T cells protected against overall and bacterial infections; late effector memory CD4(+)T cells protected against overall, bacterial, and viral infections. To the contrary, high percentage of effector- and late effector-memory subsets at 3 months among the CD8(+) T cell compartment predicted higher risks for viral infections. Patients who underwent transplantation from alternative donors represent a population with very high risk of infection. Detailed phenotypic analysis of immune reconstitution may help to evaluate infection risk and to adjust infection prophylaxis.