Inadequate local cell-mediated immunity appears crucial for the establishment of chronic HIV infection. Accumulation of regulatory T cells (Treg) at the site of HIV replication, the lymphoid organs, may influence the outcome of HIV infection. Our data provide the first evidence that chronic HIV infection changes Treg tissue distribution. Several molecules characteristics of Treg (FoxP3, CTLA-4, glucocorticoid-induced TNFR family-related receptor, and CD25) were expressed more in tonsils of untreated patients compared with antiretroviral-treated patients. Importantly, most FoxP3+ cells expressed CTLA-4, but not CD69. Furthermore, a direct correlation between FoxP3 levels and viral load was evident. In contrast, FoxP3 expression was decreased in circulating T cells from untreated patients, but normalized after initiation of treatment. Functional markers of Treg activity (indoleamine 2,3-dioxygenase, TGF-β, and CD80) were markedly increased in the tonsils of untreated patients. Our data could provide a new basis for immune-based therapies that counteract in vivo Treg and thereby reinforce appropriate antiviral immunity.
In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patientreported outcomes (PROs). Materials and methods: Treatment-naïve patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed. Results: In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms.
Prevalence of hepatitis B virus (HBV) markers, including occult HBV, has not been described in diverse cohorts among HIV-infected patients. The objective of this study was to assess prevalence and significance of active and occult HBV infection in an HIV-positive US cohort. A random sample was taken from 2 prospective multicenter treatment intervention cohorts. The sample population (n = 240) was HIV-1 infected and highly active antiretroviral therapy-naive. Prevalence of HBV serologic markers and quantitative HBV DNA were determined. Serum alanine aminotransferase (ALT) levels were measured to evaluate correlates of hepatocyte injury. A total of 64.6% of subjects demonstrated reactivity for any marker of current or past HBV infection or prior vaccination. Chronic HBV infection characterized by hepatitis B surface antigen (HBsAg) reactivity was present in 7.1% while 15.8% exhibited HB anticore IgG only. Approximately 10% of the latter group was HBV DNA positive by a polymerase chain reaction-based assay. Only patients with a serologic pattern of HBsAg or HB anticore alone reactivity had HBV DNA. Occult HBV was observed in approximately 10% of HIV-infected patients with HB anticore IgG antibody in a geographically representative national cohort. Though viral titers and serum ALT levels were low, screening of this subset of HIV-infected patients may have implications in terms of antiretroviral therapy and risk of immune reconstitution-associated flares.
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