Objectives To investigate the contribution of colon and blood CD4+ T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during ART. Design Matched sigmoid biopsies and blood samples (n=13) as well as leukapheresis (n=20) were collected from chronically HIV-infected individuals receiving ART. Subsets of CD4+ T-cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA-), central memory (TCM; CD45RA−CCR7+), effector (TEM/TM; CD45RA−CCR7−), Th17 (CCR6+CCR4+), Th1Th17 (CCR6+CXCR3+), Th1 (CCR6−CXCR3+), and Th2 (CCR6−CCR4+). Methods We used polychromatic flow cytometry for cell sorting, nested real-time PCR for HIV-DNA quantification, ELISA and flow cytometry for HIV-p24 quantification. HIV reactivation was induced by TCR-triggering in the presence/absence of all-trans retinoic acid. Results Compared to blood, the frequency of CCR6+ TM was higher in the colon. In both colon and blood compartments, CCR6+ TM were significantly enriched in HIV-DNA when compared to their CCR6− counterparts (n=13). In blood, integrated HIV-DNA levels were significantly enriched in CCR6+ versus CCR6− TCM of 4/5 individuals and CCR6+ versus CCR6− TEM of 3/5 individuals. Among blood TCM, Th17 and Th1Th17 contributed the most to the pool of cells harboring integrated HIV-DNA despite their reduced frequency compared to Th2 which were infected the least. HIV reactivation was induced by TCR triggering and/or retinoic acid exposure at higher levels in CCR6+ versus CCR6− TM, TCM, and TEM. Conclusions CCR6 is a marker for colon and blood CD4+ T-cells enriched for replication-competent HIV-DNA. Novel eradication strategies should target HIV persistence in CCR6+CD4+ T-cells from various anatomic sites.
Vascular malformation (AVM) in the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and iron deficiency anemia, especially in an aging population. While endoscopic coagulative therapy is the method of choice for controlling bleeding, a substantial number of cases require additional therapy. Adjunctive or even primary phamacotherapy may be indicated in recurrent bleeding. However, there is little evidence-based proof of efficacy for any agent. The bulk of support is derived from anecdotal reports or case series. The present review compares the outcome of AVM after no intervention, coagulative therapy or focus on pharmacological agents. Most of the literature encompasses two common AVMs, angiodysplasia and hereditary hemorrhagic telangiectasia. Similarly, the bulk of information evaluates two therapies, hormones (estrogen and progesterone) and the somatostatin analogue octreotide. Of these, the former is the only therapy evaluated in randomized trials, and the results are conflicting without clear guidelines. The latter therapy has been reported only as case reports and case series without prospective trials. In addition, other anecdotally used medications are discussed.
Objective: To explore the contribution of blood and colon myeloid cells to HIV persistence during antiretroviral therapy (ART). Design: Leukapheresis were collected from HIV-infected individuals with undetectable plasma viral load during ART (HIV+ART; n=15) and viremics untreated (HIV+; n=6). Rectal sigmoid biopsies were collected from n=8 HIV+ART. Methods: Myeloid cells (total monocytes (Mo), CD16 + /CD16-Mo, CD1c + dendritic cells (DC)) and CD4 + T-cells were isolated by MACS and/or FACS from peripheral blood. Matched myeloid and CCR6 + CD4 + T-cells were isolated from blood and rectal biopsies by FACS. Levels of early (RU5 primers), late (Gag primers), and/or integrated HIV-DNA (Alu/HIV primers) were quantified by nested real-time PCR. Replication-competent HIV was amplified by co-culturing cells from HIV+ individuals with CD3/CD28-activated CD4 + T-cells from uninfected donors.
Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.
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