We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log
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increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.
Previous studies reported a 2- to 17-fold higher risk of aortic complications (dilation or dissection) in patients with giant-cell arteritis (GCA). We aimed to determine whether or not GCA patients with large-vessel involvement demonstrated by positron emission tomography with 18F-fluorodeoxyglucose combined with computed tomography (FDG-PET/CT) have a higher risk of aortic complications. We conducted a retrospective multicenter study between 1995 and 2014. Patients were included if they fulfilled at least 3 American College of Rheumatology criteria for GCA, or 2 criteria associated with extratemporal biopsy-proven giant-cell vasculitis; they underwent at least 1 FDG-PET/CT scan at diagnosis or during follow-up; and the morphology of the aorta was assessed by medical imaging at diagnosis. Patients with an aortic complication at the time of diagnosis were excluded. Of the 130 patients included [85 women (65%), median age 70 (50–86)], GCA was biopsy proven in 77 (59%). FDG-PET/CT was performed at diagnosis in 63 (48%) patients and during the follow-up period in the 67 (52%) remaining patients. FDG-PET/CT was positive in 38/63 (60%) patients at diagnosis and in 31/67 (46%) patients when performed during follow-up (P = NS). One hundred four patients (80%) underwent at least 1 morphological assessment of the aorta during follow-up. Nine (9%) patients developed aortic complications (dilation in all and dissection in 1) at a median time of 33 (6–129) months after diagnosis. All of them displayed large-vessel inflammation on previous FDG-PET/CT. A positive FDG-PET/CT was significantly associated with a higher risk of aortic complications (P = 0.004).In our study, a positive FDG-PET/CT was associated with an increased risk of aortic complications at 5 years.
This study aimed to review and analyze the effectiveness and safety of tocilizumab in the treatment of patients with adult-onset Still's disease (AOSD). We report on two patients with AOSD who were successfully treated with tocilizumab. All published information on the use of tocilizumab in this disease was also retrieved through a systematic review of the English-language literature. Including our cases, 35 patients were given tocilizumab for AOSD (8 mg/kg/month in 22 patients). The main clinical manifestations were arthritis in all 35 patients and systemic symptoms such as fever or skin rash in 28 (80 %). Thirty-three (94 %) patients had unsuccessfully tried other immunosuppressive agents such as methotrexate, tumor necrosis factor-α blockers, or anakinra. Most of the patients achieved a response with tocilizumab, such as a prompt articular improvement in 30/35 (86 %) patients and a disappearance of systemic symptoms in 27/28 (96 %). Twenty-eight (80 %) patients tapered their steroid intakes, including seven (20 %) who were able to discontinue them. Four (11 %) patients relapsed, and two were successfully retreated with tocilizumab. Regarding safety, tocilizumab is a well-tolerated treatment, but severe side effects such as macrophage activation syndrome or cytomegalovirus reactivation are possible and require ongoing vigilance. Our findings suggest that tocilizumab should probably be proposed in refractory AOSD, as it allows for remission to be induced and the dose of steroid intakes to be reduced. It is a well-tolerated treatment that can be administered according to the therapeutic sequence of rheumatoid arthritis. Further prospective studies are required to assess the better use of this treatment (dosage and duration) and its place among other conventional treatments.
Compared with our previous studies, the proportion of NRTI- and first-generation NNRTI-related TDR has continued to decline in French seroconverters. However, subtype B-infected MSM could drive the spread of resistant HIV strains. Finally, we suggest preferring PI- or II- to NNRTI-based combinations to treat PHI patients.
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