Prevalence of anti-neutrophil cytoplasmic antibody-associated vasculitis in the south of France, using the capture-recapture method.

OBJECTIVES: This study aimed to estimate the prevalence of ANCA-associated vasculitis (AAV), ie granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), in Southern France in 2018, and evaluate differences among Europeans and non-Europeans. METHODS: This population-based, cross-sectional study used four sources (hospitals, community-based physicians, laboratories, National Health Insurance) to identify adults ≥ 15 years diagnosed with GPA, MPA or EGPA, living in Hérault and Gard in 2018. Cases were defined using the ACR/EULAR classification criteria, and if necessary, the European Medicines Agency algorithm. Prevalence estimates were standardised to the world population and capture-recapture analysis was used to assess the comprehensiveness of the estimation. The influence of geographical origin was evaluated. RESULTS: 202 patients were selected, with 86 cases of GPA (42.6%), 85 cases of MPA (42.1%), and 31 cases of EGPA (15.3%). The standardised prevalence estimates per million inhabitants for 2018 were: 103 (95%CI 84 - 125) for AAV, 48 (95%CI 35 - 64) for GPA, 39 (95%CI 28 - 53) for MPA and 16 (95%CI 9 - 26) for EGPA, 36 (95%CI 25 - 50) for anti-PR3 positive AAV, 46 (95%CI 34 - 61) for anti-MPO positive AAV, and 16 (95%CI 9 - 26) for ANCA-negative AAV. The global estimation of comprehensiveness by capture-recapture analysis was 80.5%. The number of AAV cases was higher for non-European residents (P=0.001), particularly for MPA (P<0.0001). CONCLUSION: We provide a new estimate of AAV prevalence in France and show a higher prevalence of MPA in non-European patients.

Long-Term Follow-Up of Proteinuria and Estimated Glomerular Filtration Rate in HIV-Infected Patients with Tubular Proteinuria.

OBJECTIVE: The objective of this prospective observational study was to describe the evolution of tubular proteinuria detected in HIV-infected patients, and to evaluate the impact of tenofovir disoproxil fumarate (TDF) discontinuation. METHODS: Proteinuria and estimated glomerular filtration rate (eGFR) were followed during a median duration of 32 months, in 81 HIV-infected patients with tubular proteinuria and eGFR ≥ 60 ml/min/1.73 m2 (determined using the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation). Tubular proteinuria was defined by urine protein to creatinine ratio (uPCR) ≥200 mg/g and albumin to protein ratio (uAPR) <0.4. RESULTS: Twenty per cent of patients had persistence of tubular proteinuria: TDF continuation was the main factor associated with this persistence [OR 9.0; 95%CI: 1.9-41.4; p = 0.01]. Among the 23 patients who discontinued TDF, uPCR returned below the threshold of 200 mg/g in 11 patients. Overall, eGFR decreased with a mean rate of decline of 3.8 ml/min/1.73m2/year. The decline in eGFR was lesser after discontinuation of TDF (5.8 ml/min/1.73m2/year during TDF exposure versus 3 ml/min/1.73m2/year after TDF discontinuation; p = 0.01). CONCLUSIONS: The continuation of TDF was the main factor associated with the persistence of proteinuria. Moreover, proteinuria was normalized in only half of the patients who discontinued TDF. The clinical significance of TDF-related low level of proteinuria as a factor associated with renal disease progression and bone loss remains poorly understood.

Monoclonal Gammopathy in HIV-1-Infected Patients: Factors Associated With Disappearance Under Long-Term Antiretroviral Therapy.

OBJECTIVE: Monoclonal gammopathies (MGs) associated with HIV infection are frequent but their evolution and significance are uncertain in this population at high risk of lymphoproliferative disorder. Our aim was to describe the long-term evolution of MG in HIV-infected subjects under antiretroviral therapy. METHODS: Retrospective study of HIV-1-infected adults, with a monoclonal (M) protein detected by serum protein electrophoresis and confirmed by immunofixation. Logistic regression was used to analyze factors associated with peak disappearance. RESULTS: Between September 1997 and November 2012, 1219 serum protein electrophoreses were performed on our HIV cohort, and 137 (11.3%) MGs were detected. Seventy-seven subjects met the inclusion criteria: 68% male, median age 41 years, 47% AIDS stage, median CD4 count 237 per cubic millimeter, 81% uncontrolled HIV infection with HIV viral load over 400 copies per milliliter, 32% chronic hepatitis C, and 9% chronic hepatitis B. Eighteen subjects were not included because of previous or concomitant hemopathy. With a median follow-up of 6.8 years (interquartile range, 3.9-9.1), 66.2% of subjects showed a peak disappearance. In multivariate analysis, MG disappearance was associated with HIV virologic control (odds ratio, 5.98; 95% confidence interval: 1.63 to 21.87; P = 0.007) and the absence of hepatitis C virus replication at the end of follow-up (odds ratio, 10.16; 95% confidence interval: 2.36 to 43.69; P = 0.002). One subject developed a myeloma 3 years after the diagnosis of an IgA kappa MG. CONCLUSIONS: MG associated with HIV infection concerned a young population and had favorable evolution on antiretroviral therapy in most cases. M protein disappearance was associated with HIV virologic control and the absence of chronic hepatitis C virus.

Pivotal role of HIV and EBV replication in the long-term persistence of monoclonal gammopathy in patients on antiretroviral therapy.

A high prevalence of monoclonal gammopathy (MG) has been observed in HIV-infected patients. We explored the conditions associated with long-term persistence of serum monoclonal protein (M protein) in HIV-infected patients on antiretroviral therapy (ART). Of 21 patients with MG, M protein disappeared in 12 patients (58%) over 5 years of ART. Higher level of serum γ-globulin and higher percentages of circulating plasmablasts and plasma cells were observed in patients with persistent MG compared with patients with transient MG. MG persistence was associated with the cumulative time of detectable plasma HIV RNA after ART initiation, detection of Epstein-Barr virus (EBV) DNA in plasma, and a high level of EBV DNA in B cells. Poor control of HIV replication and detectable EBV replication in plasma were both associated with long-term MG persistence in patients on ART. In the case of viral control, MG associated with HIV infection is usually transient.