RESUMO
Yellow fever (YF) vaccination is known to induce a suboptimal response in patients with autoimmune diseases (AIDs). To date, few studies have focused on the performance of 17DD-YF vaccination in patients with spondyloarthritis (SpA). In general, patients with SpA are young and have less comorbidities than other patients with AIDs, and frequently receive biological disease-modifying antirheumatic drugs (DMARDs) that may impact their response to vaccines. Taking this background information, the present study aimed to investigate whether the use of biological DMARDs, even after planned washout, or disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), would impact the overall performance of planned 17DD-YF primary vaccination in patients with SpA. For this purpose, 74 subjects were enrolled in a prospective study, including adult patients with SpA (SpA; n = 51) and a healthy control (HC; n = 23) group. Analysis of YF specific neutralizing antibodies test (PRNT), along with YF viremia and the levels of serum chemokines, cytokines, and growth factors were performed at distinct time points (D0, D3, D4, D5, D6, D7, D14, and D28). The BASDAI scores were evaluated at D0 and D180. Data demonstrated that overall, the SpA group presented lower PRNT titers and seropositivity rates as compared to the HC group (GeoMean = 112 vs. 440; 73% vs. 96%, respectively). In SpA subgroup analyses, previous biological DMARDs (BIO-IT) led to a lower PRNT titers (BIO-IT 79, 95% CI [39-150] vs. without biological DMARDs [non-BIO-IT] 159, 95% CI [94-267], p < 0.001). The non-BIO-IT group achieved a response similar to the HC group (81% vs. 96%, p = 0.112), whereas the BIO-IT group had a lower seroconversion rate (64% vs. 96% HC, p = 0.007). The BASDAI was not associated with PRNT levels and did not change after 6 months of follow-up. No differences in YF viremia were observed amongst subgroups. Higher baseline levels of serum biomarkers were observed in the BIO-IT group vs. the non-BIO-IT group, as well as in those with a BASDAI ≥ 4 vs. those with a BASDAI < 4. Increasing levels of several biomarkers were observed in SpA, especially in the BIO-IT and BASDAI ≥ 4 subgroups throughout the timeline kinetics, with impairment/disturbance in the IFN-γ/IL-10 axis around the peak of viremia (D5). Altogether, these findings suggested that the use of biological DMARDs impacts the response to the 17DD-YF vaccine, even after planned washout. Therefore, previous biological DMARD therapy, the inflammatory status prior vaccination, and impairment of the IFN-γ/IL-10 axis at the peak of viremia may determine the immunogenicity of 17DD-YF vaccination in patients with SpA.
Assuntos
Síndrome da Imunodeficiência Adquirida , Antirreumáticos , Espondilartrite , Vacina contra Febre Amarela , Febre Amarela , Adulto , Anticorpos Antivirais , Antirreumáticos/uso terapêutico , Biomarcadores , Humanos , Imunidade , Interferon gama , Interleucina-10 , Estudos Prospectivos , Espondilartrite/tratamento farmacológico , Vacinação , Viremia , Febre Amarela/prevenção & controle , Vírus da Febre AmarelaRESUMO
INTRODUCTION: Published data addressing the effectiveness of darunavir-ritonavir (DRV/r)-based therapy for multiexperienced patients in developing countries are scarce. This study evaluated the 48-week virologic and immunologic effectiveness of salvage therapy based on DRV/r for the treatment of multidrug-experienced HIV-1-infected adults in Brazil. MATERIALS AND METHODS: A multicenter retrospective cohort study was carried out with multidrug-experienced adults who were on a failing antiretroviral therapy and started a DRV/r-based salvage therapy between 2008 and 2010. The primary effectiveness end point was the proportion of patients with virologic success (plasma HIV-1 RNA <50 copies/mL at week 48). RESULTS: At 48 weeks, 73% of the patients had HIV-RNA <50 copies/mL and a mean increase of 108 CD4 cells/mm(3). Higher baseline viral load, lower baseline CD4 count, younger age, and 3 or more DRV/r-associated resistance mutations were significantly predictive of virologic failure. Concomitant use of raltegravir was strongly associated with virologic success. CONCLUSION: The use of DRV/r-based regimens for salvage therapy is an effective strategy in the clinical care setting of a developing country.